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1
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Park SB, Choi HY, Park YE, Jang S, Chun HS. High-content screening morphological analysis to evaluate hepatic apoptosis induced by plant alkaloids in a Chang cell model. Toxicology 2025; 515:154140. [PMID: 40222580 DOI: 10.1016/j.tox.2025.154140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Revised: 04/06/2025] [Accepted: 04/06/2025] [Indexed: 04/15/2025]
Abstract
As interest in plant-derived compounds and their application in the pharmaceutical and functional food industries has increased, the rapid detection of chemical toxicity has become increasingly important for developing safe products. High-content screening (HCS) can quantify cellular and organelle morphological changes through image analysis; however, most HCS studies on apoptosis, a key toxicological event, have focused on the expression of apoptosis-related genes or proteins. In this study, we aimed to verify whether apoptosis can be detected solely based on cellular morphological changes. Chang cells were treated with staurosporine (STS), a well-known apoptosis inducer, and the morphological changes in the cells were quantified using HCS assays. The correlation between these HCS morphological descriptors and apoptosis rates measured using flow cytometry was determined. Chang cells were also treated with several plant-derived alkaloids known to induce apoptosis, and the same process was performed. The correlation coefficients, which were used to evaluate the correlation between HCS descriptors and apoptosis rates after STS treatment, ranged from 0.64 to 0.98, with 13 descriptors showing significant correlations. In contrast, the highest correlation coefficients between HCS descriptors and apoptosis rates after treatment with 1 of the 12 alkaloids investigated were determined to be 0.75 (at 10 μg/ml) and 0.49 (at 100 μg/ml). The apoptosis-related morphological changes induced by STS and alkaloids were observed using confocal microscopy. The present study demonstrates that HCS assays can detect apoptosis solely based on cellular morphological changes, providing a potential tool for rapid toxicity screening in early product development.
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Affiliation(s)
- Su Been Park
- GreenTech-based Food Safety Research Group, BK21 Four, School of Food Science and Technology, Chung-Ang University, South Korea.
| | - Hwa Young Choi
- GreenTech-based Food Safety Research Group, BK21 Four, School of Food Science and Technology, Chung-Ang University, South Korea
| | - Young Eun Park
- GreenTech-based Food Safety Research Group, BK21 Four, School of Food Science and Technology, Chung-Ang University, South Korea
| | - Sihyeon Jang
- GreenTech-based Food Safety Research Group, BK21 Four, School of Food Science and Technology, Chung-Ang University, South Korea.
| | - Hyang Sook Chun
- GreenTech-based Food Safety Research Group, BK21 Four, School of Food Science and Technology, Chung-Ang University, South Korea.
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2
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Indumathi MC, Swetha K, Abhilasha KV, Siddappa S, Kumar SM, Prasad GK, Chen CH, Marathe GK. Selenium Ameliorates Acetaminophen-Induced Oxidative Stress via MAPK and Nrf2 Pathways in Mice. Biol Trace Elem Res 2024; 202:2598-2615. [PMID: 37702962 DOI: 10.1007/s12011-023-03845-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 09/05/2023] [Indexed: 09/14/2023]
Abstract
Overdose of acetaminophen (paracetamol), a widely used non-prescriptive analgesic and antipyretic medication, is one of the main causes of drug-induced acute liver failure around the world. Oxidative stress contributes to this hepatotoxicity. Antioxidants are known to protect the liver from oxidative stress. Selenium, a potent antioxidant, is a commonly used micronutrient. Here, we evaluated the protective effect of selenium on acetaminophen-induced hepatotoxicity. Treating Wistar albino mice with sodium selenite (1 mg/kg) before or after inducing hepatotoxicity with acetaminophen (150 mg/kg) significantly reduced the levels of liver injury biomarkers such as serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase. In addition, selenium-treated mice showed decreased levels of oxidative stress markers such as protein carbonyls and myeloperoxidase. Acetaminophen treatment stimulated all three mitogen-activated protein kinases (MAPKs) and Keap1 and decreased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 in liver and in isolated mouse peritoneal macrophages, which was reversed by selenium treatment. Our findings suggest that the reactive oxygen species-mediated Nrf2 and MAPK pathways are critical players in acetaminophen-induced hepatotoxicity. These key findings offer an alternative therapeutic target for addressing acetaminophen-induced hepatotoxicity.
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Affiliation(s)
| | - Kamatam Swetha
- Department of Studies in Biochemistry, 8J8C+98P, University of Mysore, Manasagangotri, Mysore, 570006, Karnataka, India
| | | | - Shiva Siddappa
- Division of Biochemistry, School of Life Sciences, 8MV2+MPG, Sri Shivarathreeshwara Nagara, JSS Academy of Higher Education and Research, Bannimantap A Layout, Bannimantap, Mysuru, Karnataka, 570015, India
| | - Shivamadhaiah Manjula Kumar
- Department of Studies in Biochemistry, 8J8C+98P, University of Mysore, Manasagangotri, Mysore, 570006, Karnataka, India
| | - Govinda Keerthi Prasad
- Department of Studies in Biochemistry, 8J8C+98P, University of Mysore, Manasagangotri, Mysore, 570006, Karnataka, India
| | - Chu-Huang Chen
- Vascular and Medicinal Research, The Texas Heart Institute, 6770 Bertner Avenue, Houston, TX, 77030, USA
| | - Gopal Kedihithlu Marathe
- Department of Studies in Biochemistry, 8J8C+98P, University of Mysore, Manasagangotri, Mysore, 570006, Karnataka, India.
- Department of Studies in Molecular Biology, 8J8C+JFP, University of Mysore, Manasagangotri, Mysore, 570006, Karnataka, India.
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Chen J, Wu J, Bai Y, Yang C, Wang J. Recent advances of single-cell RNA sequencing in toxicology research: Insight into hepatotoxicity and nephrotoxicity. CURRENT OPINION IN TOXICOLOGY 2024; 37:100462. [DOI: 10.1016/j.cotox.2024.100462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
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Wei L, Li X, Yao Y, Wang S, Ai X, Liu S. Study on the molecular mechanism of dihydromyricetin in alleviating liver cirrhosis based on network pharmacology. Chem Biol Drug Des 2024; 103:e14421. [PMID: 38230771 DOI: 10.1111/cbdd.14421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 08/31/2023] [Accepted: 12/03/2023] [Indexed: 01/18/2024]
Abstract
Dihydromyricetin (DHM) is a bioactive flavonoid extracted from Hovenia dulcis, which has various activities. In the present study, the molecular mechanism of dihydromyricetin (DHM) in relieving liver cirrhosis was investigated through network pharmacology and experimental verification. The cell model was induced by TGF-β1 activating the human hepatic stellate cell line (HSC; LX-2). The protein levels of α-SMA, collagen I, and collagen III and pathway-related proteins within LX-2 cells were detected using Western blot. EdU staining was conducted to detect cell proliferation. Immunofluorescence staining was performed to detect the expression levels of α-SMA and collagen I. Next, the drug targets of DHM were screened from the PubChem database. The differentially expressed genes in the liver cirrhosis dataset GSE14323 were identified. The expression of the identified drug targets in LX-2 cells was verified using qRT-PCR. The results showed that TGF-β1 treatment notably increased LX-2 cell viability, promoted cell proliferation, and elevated α-SMA, collagen I, and collagen III protein contents. DHM treatment could partially eliminate TGF-β1 effects, as evidenced by the inhibited cell viability and proliferation and reduced α-SMA, collagen I, and collagen III contents. After network pharmacology analysis, nine differentially expressed target genes (MMP2, PDGFRB, PARP1, BCL2L2, ABCB1, TYR, CYP2E1, SQSTM1, and IL6) in liver cirrhosis were identified. According to qRT-PCR verification, DHM could inhibit the expression of MMP2, PDGFRB, PARP1, CYP2E1, SQSTM1, and IL6, and enhance ABCB1 expression levels within LX-2 cells. Moreover, DHM inhibited mTOR and MAPK signaling pathways in TGF-β1-induced HSCs. In conclusion, DHM could inhibit HSC activation, which may be achieved via acting on MMP2, PDGFRB, PARP1, CYP2E1, SQSTM1, IL6, and ABCB1 genes and their downstream signaling pathways, including mTOR and MAPK signaling pathway.
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Affiliation(s)
- Lin Wei
- College of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, Hunan, China
| | - Xiaoying Li
- Key Laboratory of Research and Utilization of Ethnomedicinal Plant Resources of Hunan Province, College of biology and food engineering, Huaihua University, Huaihua, Hunan, China
| | - Yuanzhi Yao
- Key Laboratory of Research and Utilization of Ethnomedicinal Plant Resources of Hunan Province, College of biology and food engineering, Huaihua University, Huaihua, Hunan, China
| | - Siqi Wang
- College of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, Hunan, China
| | - Xinghui Ai
- College of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, Hunan, China
| | - Shenggui Liu
- Key Laboratory of Research and Utilization of Ethnomedicinal Plant Resources of Hunan Province, College of biology and food engineering, Huaihua University, Huaihua, Hunan, China
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Kim YJ, Kang SY, Kim MS, Lee J, Yang BR. Association between weight loss agents and elevated liver enzymes: a population-based cross-sectional study. Sci Rep 2023; 13:15796. [PMID: 37737274 PMCID: PMC10517163 DOI: 10.1038/s41598-023-41908-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 09/01/2023] [Indexed: 09/23/2023] Open
Abstract
The widespread use of body weight control agents might be related to liver enzyme elevation, but this potential association has only been documented in a few case reports. This study aimed to investigate the associations between weight loss agents and elevated liver enzymes at the population-level. We conducted a cross-sectional study using Korea National Health and Nutrition Examination Survey (KNHANES) data from 2013 to 2019. This study included 36,259 participants over 20 years of age who completed the questionnaire and had no history of hepatitis, cancer, or renal failure. In these participants, we analyzed associations between weight loss agents and elevated liver enzymes by constructing multiple logistic regression models with adjustment for confounding factors and stratified by sex, age, and body mass index. The use of weight loss agents related to liver enzyme elevation in men (adjusted odds ratio (aOR): 1.36, 95% confidence interval (CI): 1.08-1.71) and participants aged less than 40 years (aOR: 1.44, 95% CI: 1.12-1.87). Using more types of weight loss agents was associated with liver enzyme elevation (aOR: 1.31, 95% CI: 1.03-1.67 for 1 weight loss agent, aOR: 1.93, 95% CI: 0.93-3.99 for ≥ 2 weight loss agents). Elevated liver enzymes were associated with the use of traditional medicines (aOR: 1.96, 95% CI: 1.14-3.34) and dietary supplements (aOR: 1.33, 95% CI: 1.02-1.72) in men. We observed an association between weight loss agents and liver enzyme elevation in men, particularly for traditional herbal medicines and dietary supplements. To confirm the observed associations, studies higher on the evidence hierarchy are needed.
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Affiliation(s)
- Ye-Jee Kim
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seo Young Kang
- Department of Family Medicine, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu, Republic of Korea
| | - Mi-Sook Kim
- Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Joongyub Lee
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Bo Ram Yang
- College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
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Xu XT, Wang BH, Wang Q, Guo YJ, Zhang YN, Chen XL, Fang YF, Wang K, Guo WH, Wen ZZ. Idiopathic hypereosinophilic syndrome with hepatic sinusoidal obstruction syndrome: A case report and literature review. World J Gastrointest Surg 2023; 15:1532-1541. [PMID: 37555104 PMCID: PMC10405125 DOI: 10.4240/wjgs.v15.i7.1532] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 04/17/2023] [Accepted: 05/17/2023] [Indexed: 07/21/2023] Open
Abstract
BACKGROUND Hypereosinophilic syndrome (HES) is classified as primary, secondary or idiopathic. Idiopathic HES (IHES) has a variable clinical presentation and may involve multiple organs causing severe damage. Hepatic sinusoidal obstruction syndrome (HSOS) is characterized by damage to the endothelial cells of the hepatic sinusoids of the hepatic venules, with occlusion of the hepatic venules, and hepatocyte necrosis. We report a case of IHES with HSOS of uncertain etiology. CASE SUMMARY A 70-year-old male patient was admitted to our hospital with pruritus and a rash on the extremities for > 5 mo. He had previously undergone antiallergic treatment and herbal therapy in the local hospital, but the symptoms recurred. Relevant examinations were completed after admission. Bone marrow aspiration biopsy showed a significantly higher percentage of eosinophils (23%) with approximately normal morphology. Ultrasound-guided hepatic aspiration biopsy indicated HSOS. Contrast-enhanced computed tomography (CT) of the upper abdomen showed hepatic venule congestion with hydrothorax and ascites. The patient was initially diagnosed with IHES and hepatic venule occlusion. Prednisone, low molecular weight heparin and ursodeoxycholic acid were given for treatment, followed by discontinuation of low molecular weight heparin due to ecchymosis. Routine blood tests, biochemical tests, and imaging such as enhanced CT of the upper abdomen and pelvis were reviewed regularly. CONCLUSION Hypereosinophilia may play a facilitating role in the occurrence and development of HSOS.
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Affiliation(s)
- Xu-Tao Xu
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Bing-Hong Wang
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Qiang Wang
- Department of Hepatopancreatobiliary Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
| | - Yang-Jie Guo
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Yu-Ning Zhang
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Xiao-Li Chen
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Yan-Fei Fang
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Kan Wang
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Wen-Hao Guo
- Department of Pathology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Zhen-Zhen Wen
- Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou 310016, Zhejiang Province, China
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7
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Mosaddad SA, Hussain A, Tebyaniyan H. Green Alternatives as Antimicrobial Agents in Mitigating Periodontal Diseases: A Narrative Review. Microorganisms 2023; 11:1269. [PMCID: PMC10220622 DOI: 10.3390/microorganisms11051269] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 04/26/2023] [Accepted: 05/09/2023] [Indexed: 06/03/2023] Open
Abstract
Periodontal diseases and dental caries are the most common infectious oral diseases impacting oral health globally. Oral cavity health is crucial for enhancing life quality since it serves as the entranceway to general health. The oral microbiome and oral infectious diseases are strongly correlated. Gram-negative anaerobic bacteria have been associated with periodontal diseases. Due to the shortcomings of several antimicrobial medications frequently applied in dentistry, the lack of resources in developing countries, the prevalence of oral inflammatory conditions, and the rise in bacterial antibiotic resistance, there is a need for reliable, efficient, and affordable alternative solutions for the prevention and treatment of periodontal diseases. Several accessible chemical agents can alter the oral microbiota, although these substances also have unfavorable symptoms such as vomiting, diarrhea, and tooth discoloration. Natural phytochemicals generated from plants that have historically been used as medicines are categorized as prospective alternatives due to the ongoing quest for substitute products. This review concentrated on phytochemicals or herbal extracts that impact periodontal diseases by decreasing the formation of dental biofilms and plaques, preventing the proliferation of oral pathogens, and inhibiting bacterial adhesion to surfaces. Investigations examining the effectiveness and safety of plant-based medicines have also been presented, including those conducted over the past decade.
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Affiliation(s)
- Seyed Ali Mosaddad
- Student Research Committee, School of Dentistry, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran;
| | - Ahmed Hussain
- School of Dentistry, Edmonton Clinic Health Academy, University of Alberta, Edmonton, AB T6G 1C9, Canada
| | - Hamid Tebyaniyan
- Science and Research Branch, Islimic Azade University, Tehran 14878-92855, Iran
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8
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Zarei MH, Farzan M, Dehkordi ES, Lorigooini Z, Moradi MT. The effect of infusion time on Echium amoenum extract -induced hepatotoxicity in vitro. Toxicon 2023; 229:107133. [PMID: 37127122 DOI: 10.1016/j.toxicon.2023.107133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Revised: 04/01/2023] [Accepted: 04/23/2023] [Indexed: 05/03/2023]
Abstract
Echium amoenum is an annual herb native to the northern mountains of Iran which has medicinal application. Petals of Echium amoenum (Gole-Gavzaban) is one of the most valuable medicinal plants in Iranian folk medicine. The dry petals of E. amoenum have long been used as a sedative, tonic, anxiolytic and as a treatment for sore throat, cough and inflammation. Previous studies have shown that petals of E. amoenum contain four toxic pyrrolizidine alkaloids but conflicting results have been acquired in experimental studies investigating the hepatotoxicy of E. amoenum. However, the direct effect of E. amoenum on liver cells and the complete mechanisms of its possible cytotoxic effects toward these cells remain to be defined. The main aim of this study was to assay the mechanisms underlying the toxic effects of E. amoenum toward hepG2 cells. E. amoenum extract was obtained by infusion of dried petals in hot water (90 centigrade) for 15 or 30 min. Cell viability and mechanistic parameters were determined following 12 h incubation of hepG2 with E. amoenum extract that was obtained after 15 or 30 min infusion. The results indicated that E. amoenum extract exerts cytotoxic effects on hepG2 cells, probably through mitochondrial and lysosomal damage induced by glutathione depletion and oxidative stress.
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Affiliation(s)
- Mohammad Hadi Zarei
- Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
| | - Mahour Farzan
- Student Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Ebrahim Soleiman Dehkordi
- Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Zahra Lorigooini
- Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Mohammad Taghi Moradi
- Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
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Wang D, Liu J, Chen X, Chen J, Zhao T, Du J, Wang C, Meng Q, Sun H, Wang F, Liu K, Wu J. Renal transporter OAT1 and PPAR-α pathway co-contribute to icaritin-induced nephrotoxicity. Phytother Res 2023; 37:549-562. [PMID: 36331006 DOI: 10.1002/ptr.7633] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Revised: 08/24/2022] [Accepted: 09/09/2022] [Indexed: 11/06/2022]
Abstract
This study aimed to investigate the potential nephrotoxicity of icaritin and the underlying mechanism by in vitro-in vivo experiment technology combined with proteomics technology. First, icaritin showed a significant cytotoxic effect on HK-2 cells, which was accompanied by increased LDH and TNF-α in the supernatant, decreased protein expressions of Bcl-2 and increased Bax and enhanced apoptosis of HK-2 cells as measured by TUNEL staining. Moreover, icaritin induced obvious tubular damage and up-regulation of BUN and CRE levels in plasma in mice. Second, intracellular uptake of icaritin was considerably higher in hOAT1-HEK293 cells than in mock-HEK293 cells, suggesting that icaritin might accumulate in renal cells via OAT1 uptake. Importantly, icaritin caused significant changes in the PPAR signaling pathway in HK2 cells through proteomic analysis. Then, in vitro and in vivo results verified that icaritin significantly downregulated the protein expression of PPAR-α as well as downregulated APOB, ACSL3, ACSL4, and upregulated 5/12/15-HETE, implying that a lipid metabolism disorder was involved in the icaritin-induced nephrotoxicity. Finally, icaritin was found to increase the accumulation of iron and LPO levels while reducing the activity of GPX4, suggesting that ferroptosis was involved in the nephrotoxicity induced by icaritin.
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Affiliation(s)
- Dalong Wang
- College of Pharmacy, Dalian Medical University, Dalian, China.,Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, China
| | - Jing Liu
- College of Pharmacy, Dalian Medical University, Dalian, China
| | - Xiaodong Chen
- College of Pharmacy, Dalian Medical University, Dalian, China.,Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, China
| | - Jing Chen
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, China
| | - Tingting Zhao
- College of Pharmacy, Dalian Medical University, Dalian, China.,Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, China
| | - Jie Du
- College of Pharmacy, Dalian Medical University, Dalian, China.,Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, China
| | - Changyuan Wang
- College of Pharmacy, Dalian Medical University, Dalian, China.,Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, China
| | - Qiang Meng
- College of Pharmacy, Dalian Medical University, Dalian, China.,Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, China
| | - Huijun Sun
- College of Pharmacy, Dalian Medical University, Dalian, China.,Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, China
| | - Fangjun Wang
- Key Laboratory of Separation Sciences for Analytical Chemistry, Chinese Academy of Sciences, Dalian, China
| | - Kexin Liu
- College of Pharmacy, Dalian Medical University, Dalian, China.,Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, China
| | - Jingjing Wu
- College of Pharmacy, Dalian Medical University, Dalian, China.,Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, China
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10
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Nunes V, de Freitas LAR, de Freitas JR, Araújo C, Junior GN, Schinoni MI, Bessone F, Paraná R. Obliterative portal venopathy: A neglected and probably misdiagnosed disease with peculiar etiology in South America. JGH Open 2022; 6:904-909. [PMID: 36514502 PMCID: PMC9730720 DOI: 10.1002/jgh3.12840] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 10/07/2022] [Accepted: 10/26/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND AND AIM Obliterative portal venopathy (OPV) is one of the causes of non-cirrhotic portal hypertension. However, many aspects of OPV remain unclear, including the etiology, pathogenesis, and natural history. The aim of this study was to describe the clinical features of OPV in a series of patients in Brazil in whom OPV was diagnosed through liver biopsy. METHODS Forty-three consecutive adult patients with OPV were retrospectively selected as a case series based on histologic criteria, defined by the presence of at least portal fibrosis, phlebosclerosis, disappearance and/or reduction of the caliber of portal vein branches, and exclusion of cirrhosis. Clinical and laboratory data were analyzed. Clinically significant portal hypertension was considered in the presence of esophageal varices and/or ascites. RESULTS The mean age of patients at diagnosis was 44.5 ± 11 years, who were predominantly female (81%). Clinically significant portal hypertension was found in 28% of cases. The most frequent indication for liver biopsy was the elevation of liver enzymes, mostly γ-glutamyl transferase (GGT) in 76% of patients, averaging 222 IU/L (upper limit of normality up to 40 IU/L) and alanine aminotransferase (ALT) in 64%, mean 84 IU/L (38 IU/L). One-third of our patients had exposure to medications, especially herbal medicines, at the time of enzymatic changes. Other risk factors highlighted were features of autoimmunity in 25% of patients or thrombophilia in 20%. CONCLUSION OPV can be diagnosed even before the onset of portal hypertension, ALT elevation, and especially GGT elevation in most cases. Its etiology is not defined, but autoimmune diseases, thrombophilia, and the use of medications or herbal medicines may play a role.
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Affiliation(s)
- Vinícius Nunes
- Gastroenterology and Hepatology DepartmentHospital Universitário Prof Edgard SantosSalvadorBrazil
- Medical School of the Federal University of Bahia‐BrasilSalvadorBrazil
- IDORSão PauloBrazil
| | - Luiz A R de Freitas
- Department of PathologySchool of Medicine of the Federal University of BahiaSalvadorBrazil
- LPEM of the Instituto de Pesquisa Gonçalo Moniz‐FIOCRUZSalvadorBrazil
| | - Juliana R de Freitas
- Department of PathologySchool of Medicine of the Federal University of BahiaSalvadorBrazil
- LPEM of the Instituto de Pesquisa Gonçalo Moniz‐FIOCRUZSalvadorBrazil
| | - Caio Araújo
- Medical School of the Federal University of Bahia‐BrasilSalvadorBrazil
| | - Gildásio N Junior
- Medical School of the Federal University of Bahia‐BrasilSalvadorBrazil
| | - Maria I Schinoni
- Gastroenterology and Hepatology DepartmentHospital Universitário Prof Edgard SantosSalvadorBrazil
- Medical School of the Federal University of Bahia‐BrasilSalvadorBrazil
- Faculty of MedicineMedical School of the Federal University of BahiaSalvadorBrazil
| | - Fernando Bessone
- Hospital Provincial del CentenarioUniversity of Rosario School of MedicineRosarioArgentina
| | - Raymundo Paraná
- Gastroenterology and Hepatology DepartmentHospital Universitário Prof Edgard SantosSalvadorBrazil
- Medical School of the Federal University of Bahia‐BrasilSalvadorBrazil
- IDORSão PauloBrazil
- Faculty of MedicineMedical School of the Federal University of BahiaSalvadorBrazil
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11
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Matthews PC, Campbell C, Săndulescu O, Matičič M, Ruta SM, Rivero-Juárez A, van Welzen BJ, Tan BK, Garcia F, Gherlan GS, Çınar G, Hasanoğlu İ, Gmizić I, Nicolini LA, Santos L, Sargsyants N, Velikov P, Habibović S, Fourati S, Židovec-Lepej S, Herder V, Dudman S, Miron VD, Irving W, Şahin GÖ. Acute severe hepatitis outbreak in children: A perfect storm. What do we know, and what questions remain? Front Pharmacol 2022; 13:1062408. [PMID: 36506522 PMCID: PMC9732095 DOI: 10.3389/fphar.2022.1062408] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Accepted: 11/04/2022] [Indexed: 11/27/2022] Open
Abstract
During the first half of 2022, the World Health Organization reported an outbreak of acute severe hepatitis of unknown aetiology (AS-Hep-UA) in children, following initial alerts from the United Kingdom (UK) where a cluster of cases was first observed in previously well children aged <6 years. Sporadic cases were then reported across Europe and worldwide, although in most countries incidence did not increase above the expected baseline. There were no consistent epidemiological links between cases, and microbiological investigations ruled out known infectious causes of hepatitis. In this review, we explore the evidence for the role of viral infection, superimposed on a specific host genetic background, as a trigger for liver pathology. This hypothesis is based on a high prevalence of Human Adenovirus (HAdV) 41F in affected children, together with metagenomic evidence of adeno-associated virus (Adeno-associated viruses)-2, which is a putative trigger for an immune-mediated liver injury. Roles for superantigen-mediated pathology have also been explored, with a focus on the potential contribution of SARS-CoV-2 infection. Affected children also had a high frequency of the MHC allele HLA-DRB1*04:01, supporting an immunological predisposition, and may have been vulnerable to viral coinfections due to disruption in normal patterns of exposure and immunity as a result of population lockdowns during the COVID-19 pandemic. We discuss areas of ongoing uncertainty, and highlight the need for ongoing scrutiny to inform clinical and public health interventions for this outbreak and for others that may evolve in future.
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Affiliation(s)
- Philippa C. Matthews
- The Francis Crick Institute, London, United Kingdom
- Division of Infection and Immunity, University College London, London, United Kingdom
- Department of Infection, University College London Hospitals, London, United Kingdom
| | - Cori Campbell
- Nuffield Department of Medicine, University of Oxford, Oxford, England
| | - Oana Săndulescu
- Department of Infectious Diseases, National Institute for Infectious Diseases-Prof. Dr. Matei Balş, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Mojca Matičič
- Faculty of Medicine, Clinic for Infectious Diseases and Febrile Illnesses, University Medical Centre Ljubljana, University of Ljubljana, Ljubljana, Slovenia
| | - Simona Maria Ruta
- Virology Department, Stefan S. Nicolau Institute of Virology, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
| | - Antonio Rivero-Juárez
- Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba, Universidad de Córdoba, Córdoba, Spain
| | - Berend Joost van Welzen
- Department of Internal Medicine and Infectious Diseases, University Medical Centre Utrecht, Utrecht, Netherlands
| | - Boun Kim Tan
- INSERM U1052, Department of Intensive Care Unit, Hôpital Lyon Sud, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Lyon, France
| | - Federico Garcia
- Microbiology Department, Instituto de Investigacion Ibs.Granada and Ciber de Enfermedades Infecciosas (CIBERINFEC), University Hospital San Cecilio, Granada, Spain
| | - George Sebastian Gherlan
- Department of Infectious Diseases, “Dr. Victor Babes” Clinical Hospital of Infectious and Tropical Diseases, Bucharest, Romania
| | - Güle Çınar
- Department of Infectious Diseases and Clinical Microbiology, Ankara University Faculty of Medicine, Ankara, Turkey
| | - İmran Hasanoğlu
- Department of Infectious Disease and Clinical Microbiology, Ankara City Hospital, Ankara Yıldırım Beyazıt University, Ankara, Turkey
| | - Ivana Gmizić
- Clinic for Infectious and Tropical Diseases, University Clinical Center of Serbia, Belgrade, Serbia
| | - Laura Ambra Nicolini
- Division of Infectious Diseases , Ospedale Policlinico San Martino, Genova, Italy
| | - Lurdes Santos
- Nephrology and Infectious Diseases R&D, Infectious Diseases Intensive Care Unit, Faculty of Medicine of University of Porto, Centro Hospitalar Universitário São João, I3S - Instituto de Investigação e Inovaçãoem Saúde, University of Porto, Porto, Portugal
| | - Narina Sargsyants
- Ministry of Health, National Centre for Infectious Diseases, National Institute of Health, Yerevan, Armenia
| | - Petar Velikov
- Infectious Diseases Hospital Prof. Ivan Kirov and Department of Infectious Diseases, Parasitology and Tropical Medicine, Medical University of Sofia, Sofia, Bulgaria
| | - Selma Habibović
- Department of Microbiology, Public Health Institute Novi Pazar, Novi Pazar, Serbia
| | - Slim Fourati
- Department of Virology, INSERM, Henri Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Institut Mondor de Recherche Biomédicale, Université Paris-Est, Créteil, France
| | - Snježana Židovec-Lepej
- Department of Immunological and Molecular Diagnostics, University Hospital for Infectious Diseases “Dr Fran Mihaljevic”, Zagreb, Croatia
| | - Vanessa Herder
- Medical Research Council-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, United Kingdom
| | - Susanne Dudman
- Department of Microbiology, Oslo University Hospital, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Victor Daniel Miron
- National Institute for Mother and Child Health “Alessandrescu-Rusescu”, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - William Irving
- NIHR Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, United Kingdom
| | - Gülşen Özkaya Şahin
- Department of Laboratory Medicine, Section of Clinical Microbiology, Region Skåne, Lund, Sweden
- Department of Translational Medicine, Lund University, Malmö, Sweden
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12
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Boye AT, Ekanem PE, Hailu TB, Hordofa ID, Asfaw MS. Histopathological Evaluation of Ethanolic Leaf Extract of Lippia adoensis on Liver, Kidney, and Biochemical Parameters in Swiss Albino Mice. HEPATIC MEDICINE : EVIDENCE AND RESEARCH 2022; 14:123-133. [PMID: 36171754 PMCID: PMC9512065 DOI: 10.2147/hmer.s370927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Accepted: 09/07/2022] [Indexed: 11/23/2022]
Abstract
Background Eighty percent of Ethiopians use traditional medicine, one of which is the leaf of Lippea adoensis. Objective To investigate subacute toxicity of aqueous extracts of L. adoensis leaves on the liver and kidney and biochemical parameters in Swiss albino mice. Methods LD50 was assessed with nine experimental groups and one control group of adult female Swiss albino mice (five in each group). In the subacute study, 40 mice of both sexes were randomly divided into four groups of ten mice (both sexes) per group. Group I served as controls and received distilled water and feed only. Groups II-IV were used as treatment groups. They received calculated doses of aqueous leaf extracts orally at doses of 500 mg/kg, 1000 mg/kg, and 2000 mg/kg body weight, respectively. Results Since 80% of deaths occurred at the 10,000 mg/kg body-weight dose in this experiment, LD50 was considered to be <10,000 mg/kg. In the subacute test, general signs of toxicity like hypoactivity, piloerection, lethargy, and a single episode of convulsion were observed at the 2000 mg/kg dose. Beginning from the third week of administration, both male and female mice receiving 500 mg/kg and 2000 mg/kg and all treatment groups in the fourth week showed significant (P<0.05) weight loss compared to controls. Biochemical parameters were found to increase in all groups treated with ethanolic leaf extracts. Several histopathological changes like congestion, hemorrhage, severe necrosis, and infiltration of inflammatory cells in both liver and kidney in the L. adoensis-treated rats were observed at all doses. Conclusion In the present study, the ethanolic leaf extracts of L. adoensis produced dose-dependent weight loss and histopathological and biochemical changes in Swiss albino mice.
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Affiliation(s)
- Abayneh Tunta Boye
- Department of Anatomy, College of Health Sciences, Woldia University, Woldia, Ethiopia
| | - Peter Etim Ekanem
- Department of Anatomy, College of Health Sciences, Mekelle University, Mekelle, Ethiopia
| | | | - Ifa Dereje Hordofa
- Department of Anatomy, College of Health Sciences, Salale University, Salale, Ethiopia
| | - Mulu Shiferaw Asfaw
- Department of Anatomy, College of Health Sciences, Woldia University, Woldia, Ethiopia
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Abstract
Acute liver failure (ALF) in children, irrespective of cause, is a rapidly evolving catastrophic clinical condition that results in high mortality and morbidity without prompt identification and intervention. Massive hepatocyte necrosis impairs the synthetic, excretory, and detoxification abilities of the liver, with resultant coagulopathy, jaundice, metabolic disturbance, and encephalopathy. Extrahepatic organ damage, multiorgan failure, and death result from circulating inflammatory mediators released by the hepatocytes undergoing necrosis. There are yet no treatment options available for reversing or halting hepatocellular necrosis, thus current therapy focuses on supporting failing organs and preventing life threatening complications pending either spontaneous liver recovery or transplantation. The aims of this review are to define pediatric acute liver failure (PALF), understand the pathophysiologic processes that lead to multiorgan failure, to describe the consequences of a failing liver on extrahepatic organs, to enumerate the critical care challenges encountered during PALF management, and to describe pharmacologic and extracorporeal options available to support a critically ill child with ALF in the intensive care unit.
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Affiliation(s)
- Divya G Sabapathy
- Department of Pediatrics, Division of Pediatric Critical Care Medicine and Liver ICU, Baylor College of Medicine, 1, Baylor Plaza, Houston, TX 77030, USA
| | - Moreshwar S Desai
- Department of Pediatrics, Division of Pediatric Critical Care Medicine and Liver ICU, Baylor College of Medicine, 1, Baylor Plaza, Houston, TX 77030, USA.
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14
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Kohn OF, Lew SQ, Wong SSM, Sam R, Chen HC, Raimann JG, Leehey DJ, Tzamaloukas AH, Ing TS. Using herbs medically without knowing their composition: are we playing Russian roulette? Curr Med Res Opin 2022; 38:847-852. [PMID: 35362342 DOI: 10.1080/03007995.2022.2061706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Herbal medicine, a form of complementary and alternative medicine (CAM), is used throughout the world, in both developing and developed countries. The ingredients in herbal medicines are not standardized by any regulatory agency. Variability exists in the ingredients as well as in their concentrations. Plant products may become contaminated with bacteria and fungi during storage. Therefore, harm can occur to the kidney, liver, and blood components after ingestion. We encourage scientific studies to identify the active ingredients in herbs and to standardize their concentrations in all herbal preparations. Rigorous studies need to be performed in order to understand the effect of herbal ingredients on different organ systems as well as these substances' interaction with other medications.
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Affiliation(s)
- Orly F Kohn
- Pritzker School of Medicine, University of Chicago, Chicago, IL, USA
| | - Susie Q Lew
- School of Medicine and Health Sciences, George Washington University, Washington, DC, USA
| | - Steve Siu-Man Wong
- Department of Nephrology, Scarborough Health Network, Scarborough, Canada
| | - Ramin Sam
- San Francisco School of Medicine, Zuckerberg San Francisco General Hospital, University of California, San Francisco, CA, USA
| | - Hung-Chun Chen
- Division of Nephrology, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jochen G Raimann
- Research Division, Renal Research Institute, New York, New York, USA
| | - David J Leehey
- Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA
| | - Antonios H Tzamaloukas
- Raymond G. Murphy Veterans Affairs Medical Center, University of New Mexico School of Medicine, Albuquerque, NM, USA
| | - Todd S Ing
- Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA
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15
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Herb-Induced Liver Injury—A Challenging Diagnosis. Healthcare (Basel) 2022; 10:healthcare10020278. [PMID: 35206892 PMCID: PMC8872293 DOI: 10.3390/healthcare10020278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 01/23/2022] [Accepted: 01/27/2022] [Indexed: 12/02/2022] Open
Abstract
Herb-induced liver injury (HILI) can be caused by supplements containing herbs, natural products, and products used in traditional medicine. Herbal products’ most common adverse reaction is hepatotoxicity. Almost every plant part can be used to make herbal products, and these products can come in many different forms, such as teas, powders, oils, creams, capsules, and injectables. HILI incidence and prevalence are hard to estimate and vary from study to study because of insufficient large-scale prospective studies. The diagnosis of HILI is a challenging process that requires not only insight but also a high degree of suspicion by the clinician. HILI presents with unspecific symptoms and is a diagnosis of exclusion. For diagnosis, it is necessary to make a causality assessment; the Council for International Organizations of Medical Sciences assessment is the preferred method worldwide. The most effective treatment is the suspension of the use of the suspected herbal product and close monitoring of liver function. The objective of this review is to highlight the necessary steps for the clinician to follow to reach a correct diagnosis of herb-induced liver injury. Further studies of HILI are needed to better understand its complexity and prevent increased morbidity and mortality.
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16
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KARA H, BAYIR A, KORKMAZ H, TALAY F, AK A. Hepatotoxicity caused by bay leaf (Laurus nobilis): A case report. JOURNAL OF EMERGENCY MEDICINE CASE REPORTS 2021. [DOI: 10.33706/jemcr.972191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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17
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Khairy WA, Nasser HA, Sarhan MD, El Shamy AA, Galal YS. Prevalence and Predictors of Self-Medication with Antifungal Drugs and Herbal Products Among University Students: A Cross-Sectional Study from Egypt. Risk Manag Healthc Policy 2021; 14:2191-2200. [PMID: 34079406 PMCID: PMC8166349 DOI: 10.2147/rmhp.s308400] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 05/09/2021] [Indexed: 11/23/2022] Open
Abstract
Background and Purpose Irrational use of drugs for self-medication (SM) is a worldwide public health problem which results in treatment failure, economic loss, and increased burden of morbidity and mortality. Thus, the purpose of this study was to explore SM with antifungal drugs and herbal products among university students in Egypt. Methods A cross-sectional sectional study was conducted over 7 months among 403 university students in Egypt. The students were invited to complete a self-administered questionnaire through an online Google form. Questionnaire items included socio-demographic characteristics of the students, practice of and attitude towards SM with antifungal drugs, and SM with herbal products. Results Prevalence of SM with antifungal drugs among students stood at 38.2%. The main reasons for SM with antifungal drugs were perceiving their health problem as being minimal, followed by having fears of a doctor’s visit. About 73% of the students thought that SM was not a safe practice. Older age (AOR = 1.5, 95% CI= 1.3–1.8), affiliation to a private university (AOR = 3.7, 95% CI= 2.2–6.4), and being a medical student (AOR =2.4, 95% CI= 1.3–4.5) were the significant predictors of SM with antifungal drugs. A high prevalence of SM with herbal products (70.7%) was reported, with most students having used some form of herbal weight loss preparation (64%). Being a Cairo resident (AOR= 2.4, 95% CI =1.5–3.8, P<0.05) and being a medical student (AOR= 2.1, 95% CI =1.3–3.4, P<0.05) were the significant predictors of SM with herbal products. Conclusion In the current study, SM was common among Egyptian university students. Providing counseling and public health education to university students with regards to SM is crucial. Implementing strict regulations and the full enforcement of excitant laws pertaining to the use of medication supplies is also needed. Herbal products should face the scrutiny of evidence-based medicine. Further studies are needed to evaluate the impact of SM among university students.
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Affiliation(s)
- Walaa Ahmed Khairy
- Public Health and Community Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hebatallah A Nasser
- Microbiology Department, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt
| | - Mai D Sarhan
- Family Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Aliaa Ali El Shamy
- Microbiology Department, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt
| | - Yasmine Samir Galal
- Public Health and Community Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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18
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Di Giorgio A, Bartolini E, Calvo PL, Cananzi M, Cirillo F, Della Corte C, Dionisi-Vici C, Indolfi G, Iorio R, Maggiore G, Mandato C, Nebbia G, Nicastro E, Pinon M, Ranucci G, Sciveres M, Vajro P, D'Antiga L. Diagnostic Approach to Acute Liver Failure in Children: A Position Paper by the SIGENP Liver Disease Working Group. Dig Liver Dis 2021; 53:545-557. [PMID: 33775575 DOI: 10.1016/j.dld.2021.03.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 02/28/2021] [Accepted: 03/04/2021] [Indexed: 02/06/2023]
Abstract
Acute liver failure (ALF) is a clinical condition characterized by the abrupt onset of coagulopathy and biochemical evidence of hepatocellular injury, leading to rapid deterioration of liver cell function. In children, ALF has been characterized by raised transaminases, coagulopathy, and no known evidence of pre-existing chronic liver disease; unlike in adults, the presence of hepatic encephalopathy is not required to establish the diagnosis. Although rare, ALF has a high mortality rate without liver transplantation (LT). Etiology of ALF varies with age and geographical location, although it may remain indeterminate in a significant proportion of cases. However, identifying its etiology is crucial to undertake disease-specific management and evaluate indication to LT. In this position statement, the Liver Disease Working Group of the Italian Society of Gastroenterology, Hepatology and Nutrition (SIGENP) reviewed the most relevant studies on pediatric ALF to provide recommendations on etiology, clinical features and diagnostic work-up of neonates, infants and children presenting with ALF. Recommendations on medical management and transplant candidacy will be discussed in a following consensus conference.
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Affiliation(s)
- A Di Giorgio
- Paediatric Liver, GI and Transplantation, ASST-Hospital Papa Giovanni XXIII, Piazza OMS1, Bergamo 24127, Italy.
| | - E Bartolini
- Department Neurofarba, University of Florence and Liver Unit, Meyer Children's University Hospital, Florence, Italy
| | - P L Calvo
- Paediatric Gastroenterology Unit, Regina Margherita Children's Hospital Azienda Ospedaliera-Universitaria Citta della Salute e della Scienza di Torino, University of Torino, Torino, Italy
| | - M Cananzi
- Unit of Pediatric Gastroenterology and Hepatology, Dpt. of Women's and Children's Health, University Hospital of Padova, Italy
| | - F Cirillo
- Paediatric Department and Transplantation, Ismett, Palermo, Italy
| | - C Della Corte
- Paediatric Gastroenterology, Hepatology, Nutrition and Liver Transplantation, IRCCS Bambino Gesù Paediatric Hospital, Rome, Italy
| | - C Dionisi-Vici
- Division of Metabolic Diseases, Bambino Gesù Children's Hospital IRCCS, Rome, Italy
| | - G Indolfi
- Department Neurofarba, University of Florence and Liver Unit, Meyer Children's University Hospital, Florence, Italy
| | - R Iorio
- Paediatric Liver Unit, Department of Translational Medical Science, University of Naples Federico II, Naples, Italy
| | - G Maggiore
- Paediatric Gastroenterology, Hepatology, Nutrition and Liver Transplantation, IRCCS Bambino Gesù Paediatric Hospital, Rome, Italy
| | - C Mandato
- Department of Pediatrics, Santobono-Pausilipon Children's Hospital, Naples, Italy
| | - G Nebbia
- Pediatric Liver Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - E Nicastro
- Paediatric Liver, GI and Transplantation, ASST-Hospital Papa Giovanni XXIII, Piazza OMS1, Bergamo 24127, Italy
| | - M Pinon
- Paediatric Gastroenterology Unit, Regina Margherita Children's Hospital Azienda Ospedaliera-Universitaria Citta della Salute e della Scienza di Torino, University of Torino, Torino, Italy
| | - G Ranucci
- Department of Pediatrics, Santobono-Pausilipon Children's Hospital, Naples, Italy
| | - M Sciveres
- Paediatric Department and Transplantation, Ismett, Palermo, Italy
| | - P Vajro
- Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana" Section of Pediatrics, University of Salerno, Baronissi (Salerno), Italy
| | - L D'Antiga
- Paediatric Liver, GI and Transplantation, ASST-Hospital Papa Giovanni XXIII, Piazza OMS1, Bergamo 24127, Italy
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19
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KamaŞ D, Karatepe A, Soylak M. Vortex-assisted magnetic solid phase extraction of Pb and Cu in some herb samples on magnetic multiwalled carbon nanotubes. Turk J Chem 2021; 45:210-218. [PMID: 33679164 PMCID: PMC7925297 DOI: 10.3906/kim-2009-26] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 11/26/2020] [Indexed: 11/03/2022] Open
Abstract
This study is the development of a new solid phase extraction method based on using magnetic multiwalled carbon nanotubes impregnated with 1-(2-pyridylazo)2-naphthol (PAN) for separation, preconcentration, and flame atomic absorption spectrometric determination of Pb(II) and Cu(II). Optimization of the method was done by investigating pH effect, amount of magnetic multiwalled carbon nanotubes impregnated with PAN, eluent type and volume, matrix effects, and volume of the sample. The optimum adsorbent amount was found to be 75 mg and the optimum pH value was found as 5.5. The detection limits were 16.6 μg L-1 for Pb(II) and 18.9 μg L-1 for Cu(II). The relative standard deviations (RSD%) were less than 4%. Two certified reference materials: SPS-WW2 wastewater and NCS-DC73349 (bush branches and leaves) were used to test the validation of the method. The method was successfully applied to the analysis of Pb(II) and Cu(II) ions in daisy, mint, paprika, sage, rosemary, daphne leaves, heather, green tea, andViburnum opulussamples.
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Affiliation(s)
- Dilek KamaŞ
- Department of Chemistry, Faculty of Arts and Science, Nevşehir Hacı Bektaş Veli University, Nevşehir Turkey
| | - Aslıhan Karatepe
- Department of Chemistry, Faculty of Arts and Science, Nevşehir Hacı Bektaş Veli University, Nevşehir Turkey
| | - Mustafa Soylak
- Department of Chemistry, Faculty of Sciences, Erciyes University, Kayseri Turkey
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Gwee K, Holtmann G, Tack J, Suzuki H, Liu J, Xiao Y, Chen M, Hou X, Wu D, Toh C, Lu F, Tang X. Herbal medicines in functional dyspepsia-Untapped opportunities not without risks. Neurogastroenterol Motil 2021; 33:e14044. [PMID: 33258198 PMCID: PMC7900952 DOI: 10.1111/nmo.14044] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 10/12/2020] [Accepted: 11/02/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND Contemporary treatments for functional dyspepsia have limitations. Herbal medicine has been suggested as adjunctive treatment. With growing scientific recognition and public interests, an in-depth review of this is timely. AIMS/PURPOSE To evaluate the therapeutic potential and problems that may be associated with the adoption of herbal medicines in functional dyspepsia. METHODS We reviewed the treatment landscape of functional dyspepsia and assessed the scientific community's interest in herbal medicine. Preclinical pharmacological and clinical trial data were reviewed for several herbal medicines available in the market. Challenges associated with adoption of herbal medicine in mainstream medicine were critically evaluated. RESULTS We found that herbal medicines frequently comprise a combination of herbs with multiple reported pharmacological effects on gastrointestinal motility and secretory functions, as well as cytoprotective and psychotropic properties. We identified a number of commercially available herbal products that have undergone rigorous clinical trials, involving large numbers of well-defined subjects, reporting both efficacy and safety for functional dyspepsia. Persisting concerns include lack of rigorous assessments for majority of products, toxicity, consistency of ingredients, dose standardizations, and quality control. We provide a quality framework for its evaluation. CONCLUSIONS We commend herbal medicine as a viable future option in managing functional dyspepsia. An attractive appeal of herbal medicine is the prospect to simultaneously target multiple pathophysiological mechanisms. Wider adoption and acceptance of herbal medicines in treatment algorithms of functional dyspepsia will require the application of the scientific rigor expected of chemical therapies, to all stages of their development and evaluation.
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Affiliation(s)
- Kok‐Ann Gwee
- Department of MedicineYong Loo Lin School of MedicineNational University of Singapore and Gleneagles HospitalSingapore CitySingapore
| | - Gerald Holtmann
- Faculty of Medicine & Faculty of Health & Behavioural SciencesUniversity of Queensland and Department of Gastroenterology & HepatologyPrincess Alexandra HospitalWoolloongabbaQueenslandAustralia
| | - Jan Tack
- Department of GastroenterologyUniversity Hospitals LeuvenLeuvenBelgium
| | - Hidekazu Suzuki
- Division of Gastroenterology and HepatologyDepartment of Internal MedicineTokai University School of MedicineTokyoJapan
| | - Jinsong Liu
- Gastroenterology DepartmentWuhan Union HospitalHuazhong Science & Technology UniversityWuhanChina
| | - Yinglian Xiao
- Division of Gastroenterology and HepatologyThe First Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
| | - Min‐Hu Chen
- Division of Gastroenterology and HepatologyThe First Affiliated HospitalSun Yat‐sen UniversityGuangzhouChina
| | - Xiaohua Hou
- Division of GastroenterologyWuhan Union HospitalHuazhong Science & Technology UniversityWuhanChina
| | - Deng‐Chyang Wu
- Division of GastroenterologyDepartment of Internal Medicine, and Department of MedicineCollege of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
| | - Clarissa Toh
- Independent ResearcherStomach, Liver & Bowel CentreGleneagles HospitalSingapore CitySingapore
| | - Fang Lu
- Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijingChina
| | - Xu‐Dong Tang
- Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijingChina
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21
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The Subchronic Toxic Effects of Mosla chinensis Maxim in Normal Rats. BIOMED RESEARCH INTERNATIONAL 2020; 2020:4521586. [PMID: 33506006 PMCID: PMC7814957 DOI: 10.1155/2020/4521586] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 11/21/2020] [Accepted: 12/08/2020] [Indexed: 12/16/2022]
Abstract
Background The aim of this work was to study the toxic effects and target organs of Mosla chinensis Maxim (MCM) in rats and provide theoretical basis for clinical medication. Methods The subchronic toxicity study was conducted on 60 male and female SD rats using the fixed-dose method for the treatment groups and 20 male and female SD rats for the control. At the subchronic toxicity study, the water extract of MCM with fixed doses of 0.2 g/kg/day, 2 g/kg/day, and 20 g/kg/day was administered for 90 days intragastric, and the control group was given the same amount of distilled water. After 90 days, the general conditions of the rats were observed. Assessment on safety of the extract was conducted by a subchronic toxicity test which mainly examined alteration occurrence in gut flora and urine metabolism. Results There was no significant difference in physical signs, reactivity, and stool characteristics in the four groups. Compared with the control group, the number of red blood cells in the male 2 g/kg/day group and the female 0.2 g/kg/day group was significantly different (P < 0.05). The detection of serum biochemical indicators showed that MCM has an effect on liver and kidney function but has no physiological significance. The level of low-density lipoprotein in male rats was lower than that in the control group (P < 0.05). Compared with the control group, the blood glucose levels of female rats in the 0.2 g/kg/day, 2 g/kg/day, and 20 g/kg/day groups were significantly increased (P < 0.05). As far as the diversity of intestinal flora is concerned, feeding MCM for 90 days has an influence on the distribution of intestinal flora. The content of lactic acid bacteria increased, and the ratio of hard bacteria to Bacteroides (f/b) was also affected, but there was no significant difference. Conclusions These findings showed that the long-term intragastric administration of the MCM is safe to use within its dose recommendation. But it could have a slight effect on the metabolism of uric acid by changing the composition of intestinal flora and affecting the metabolism of tryptophan.
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22
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Teucrium polium Alters the Vascular Branching Pattern and VEGF-A Expression in the Chick Extra-Embryonic Membrane Model. Jundishapur J Nat Pharm Prod 2020. [DOI: 10.5812/jjnpp.68649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background: The Teucrium polium is used in traditional medicine for the treatment of various diseases, including inflammations, rheumatism, diabetes, and ulcers. While this herb and its aqueous extract have been consumed in Iran for hypoglycemia treatment, medicine has proved several side effects such as hepatitis, vomiting, changes in the kidney functions, and allergic responses. Also, using this herb is not safe during pregnancy or lactation. The chick embryo is a live animal model applicable for assessing the pathological property of herbs. In this regard, some details of the embryonic vascular toxicity of the Teucrium polium were evaluated via a chick embryo model. Objectives: The current study assessed vessels' alteration in the chick's extra embryonic membrane following Teucrium polium treatment. Change in molecular cues involved in early embryonic angiogenesis has also been investigated. Methods: The eggs of the chicken were divided into three equal treatment groups; as follow: first group one: considered as a sham, next groups: herbal extract that eggs injected with T. polium extract of 3 (150 µg/50 µL) or 6 (300 µg/50 µL) mg/kg, respectively. Results: The anti-angiogenic effect of the herb extract in which vessel area, total vessel length, and vascular branching decreased, whereas lacunarity increased in a dose-dependent manner. VEGF-A expression was also down-regulated in herb-exposed extra-embryonic membranes. Concerns regarding the side effects of T. polium during pregnancy were confirmed. Conclusions: We conclude that changes in early vascular expansion and gene expression might finally lead to developmental defects in embryos following consumption of T. polium. Thus, this herb's consumption should be decreased during embryonic development, and clinicians should limit the herb prescription in pregnant women, particularly at dosages > 3 mg/kg.
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Clinical Evaluation of the Safety and Effectiveness of Heptonica: A Ghanaian Hepatorestorative Polyherbal Product. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:9596182. [PMID: 32655671 PMCID: PMC7327574 DOI: 10.1155/2020/9596182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Accepted: 06/03/2020] [Indexed: 11/28/2022]
Abstract
The incidence of liver diseases is increasing globally, and many patients in developing countries are resorting to the use of herbal products as treatment. This study was aimed at establishing the safety and effectiveness outcomes for patients with deranged liver panel treated with a Ghanaian finished polyherbal product. The product Heptonica is prepared by CPMR from three medicinal plants: Bidens pilosa, Citrus aurantifolia, and Trema orientalis. Fifty (50) participants with clinical and biochemical signs of liver impairment were purposively recruited and treated for a period of 28 days. Participants received Heptonica at a dose of 30 mL 8 hourly after meals for the treatment period. Clinical and biochemical evaluation (liver panel test, renal function test, haematology, and urinalysis) of subjects for the safety and effectiveness of the product was undertaken at days 0 (baseline), 14, and 28. Compared to the baseline values, Heptonica did not have any untoward effect on renal function, haematological parameters, and urine parameters of subjects. Clinical and liver panel results of the participants also improved compared to the baseline: serum aspartate transaminase (AST) (p < 0.0001), alanine transaminase (ALT) (p < 0.0001), gamma-glutamyltransferase (GGT) (p- 0.0013), total bilirubin (p-0.0136), direct bilirubin (p < 0.0001), total proteins (p-0.0409), and alkaline phosphates (p- 0.0284). Level of albumin showed no significant difference within the study period. The outcome of this study indicates Heptonica has hepatorestorative action with no observable toxicity and can be used with confidence as indicated as a liver tonic.
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Quantitative proteomics analysis of Fructus Psoraleae-induced hepatotoxicity in rats. Chin J Nat Med 2020; 18:123-137. [PMID: 32172948 DOI: 10.1016/s1875-5364(20)30013-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Indexed: 01/08/2023]
Abstract
Fructus Psoraleae, which is commonly consumed for the treatment of osteoporosis, bone fracture, and leucoderma, induces liver injury. This study investigated the pathogenesis of the ethanol extract of Fructus Psoraleae (EEFP)-induced liver injury in rats. EEFP (1.35, 1.80, and 2.25 g·kg-1) was administrated to Sprague Dawley (SD) rats for 30 d. We measured liver chemistries, histopathology, and quantitative isobaric tags for relative and absolute quantitation (iTRAQ)-based protein profiling. EEFP demonstrated parameters suggestive of liver injury with changes in bile secretion, bile flow rate, and liver histopathology. iTRAQ analysis showed that a total of 4042 proteins were expressed in liver tissues of EEFP-treated and untreated rats. Among these proteins, 81 were upregulated and 32 were downregulated in the treatment group. KEGG pathway analysis showed that the drug metabolic pathways of cytochrome P450, glutathione metabolism, glycerolipid metabolism, and bile secretion were enriched with differentially expressed proteins. The expression of key proteins related to the farnesoid X receptor (FXR), i.e., the peroxisome proliferators-activated receptor alpha (PPAR-α), were downregulated, and multidrug resistance-associated protein 3 (MRP3) was upregulated in the EEFP-treated rats. Our results provide evidence that EEFP may induce hepatotoxicity through various pathways. Furthermore, our study demonstrates changes in protein regulation using iTRAQ quantitative proteomics analysis.
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Suroowan S, Mahomoodally MF. Herbal Medicine of the 21st Century: A Focus on the Chemistry, Pharmacokinetics and Toxicity of Five Widely Advocated Phytotherapies. Curr Top Med Chem 2020; 19:2718-2738. [PMID: 31721714 DOI: 10.2174/1568026619666191112121330] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Revised: 08/02/2019] [Accepted: 09/25/2019] [Indexed: 12/25/2022]
Abstract
Widely advocated for their health benefits worldwide, herbal medicines (HMs) have evolved into a billion dollar generating industry. Much is known regarding their wellness inducing properties, prophylactic and therapeutic benefits for the relief of both minor to chronic ailment conditions given their long-standing use among various cultures worldwide. On the other hand, their equally meaningful chemistry, pharmacokinetic profile in humans, interaction and toxicity profile have been poorly researched and documented. Consequently, this review is an attempt to highlight the health benefits, pharmacokinetics, interaction, and toxicity profile of five globally famous HMs. A systematic literature search was conducted by browsing major scientific databases such as Bentham Science, SciFinder, ScienceDirect, PubMed, Google Scholar and EBSCO to include 196 articles. In general, ginsenosides, glycyrrhizin and curcumin demonstrate low bioavailability when orally administered. Ginkgo biloba L. induces both CYP3A4 and CYP2C9 and alters the AUC and Cmax of conventional medications including midazolam, tolbutamide, lopinavir and nifedipine. Ginsenosides Re stimulates CYP2C9, decreasing the anticoagulant activity of warfarin. Camellia sinensis (L.) Kuntze increases the bioavailability of buspirone and is rich in vitamin K thereby inhibiting the activity of anticoagulant agents. Glycyrrhiza glabra L. displaces serum bound cardiovascular drugs such as diltiazem, nifedipine and verapamil. Herbal medicine can directly affect hepatocytes leading to hepatoxicity based on both intrinsic and extrinsic factors. The potentiation of the activity of concurrently administered conventional agents is potentially lethal especially if the drugs bear dangerous side effects and have a low therapeutic window.
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Affiliation(s)
- S Suroowan
- Department of Health Sciences, Faculty of Science, University of Mauritius, Reduit, Mauritius
| | - M F Mahomoodally
- Department of Health Sciences, Faculty of Science, University of Mauritius, Reduit, Mauritius.,Institute of Research and Development, Duy Tan University, Da Nang 550000, Vietnam
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Rakib A, Ahmed S, Islam MA, Haye A, Uddin SMN, Uddin MMN, Hossain MK, Paul A, Emran TB. Antipyretic and hepatoprotective potential of Tinospora crispa and investigation of possible lead compounds through in silico approaches. Food Sci Nutr 2020; 8:547-556. [PMID: 31993178 PMCID: PMC6977484 DOI: 10.1002/fsn3.1339] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 10/31/2019] [Accepted: 11/25/2019] [Indexed: 01/02/2023] Open
Abstract
This research describes an investigation of the antipyretic and hepatoprotective properties of both a crude organic extract and various subfractions of the ethnomedicinal plant Tinospora crispa, using appropriate animal models. In an attempt to identify potential lead hepatoprotective compounds, in silico experiments were utilized. Antipyretic activity was assessed via the Brewer's yeast-induced pyrexia method, while hepatoprotective effects were evaluated in a carbon tetrachloride (CCl4)-induced animal model. A computer-aided prediction of activity spectra for substances (PASS) model was applied to a selection of documented phytoconstituents, with the aim of identifying those compounds with most promising hepatoprotective effects. Results were analyzed using Molinspiration software. Our results showed that both the methanol extract (METC) and various subfractions (pet ether, PEFTC; n-hexane, NHFTC; and chloroform, CFTC) significantly (p < .05) reduced pyrexia in a dose-dependent manner. In CCl4-induced hepatotoxicity studies, METC ameliorated elevated hepatic markers including serum alanine amino transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP), and total bilirubin. Malondialdehyde (MDA) levels were significantly reduced, while superoxide dismutase (SOD) levels were significantly increased. Among a selection of metabolites of T. crispa, genkwanin was found to be the most potent hepatoprotective constituent using PASS predictive models. These results demonstrate that both the methanolic extract of T. crispa and those fractions containing genkwanin may offer promise in reducing pyrexia and as a source of potential hepatoprotective agents.
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Affiliation(s)
- Ahmed Rakib
- Department of PharmacyFaculty of Biological ScienceUniversity of ChittagongChittagongBangladesh
| | - Shahriar Ahmed
- Department of PharmacyFaculty of Biological ScienceUniversity of ChittagongChittagongBangladesh
| | - Md. Ashiqul Islam
- Department of PharmacyFaculty of Biological ScienceUniversity of ChittagongChittagongBangladesh
| | - Abdul Haye
- Department of Forensic MedicineUniversity of Science and Technology ChittagongChittagongBangladesh
| | - S. M. Naim Uddin
- Department of PharmacyFaculty of Biological ScienceUniversity of ChittagongChittagongBangladesh
| | | | - Mohammed Kamrul Hossain
- Department of PharmacyFaculty of Biological ScienceUniversity of ChittagongChittagongBangladesh
| | - Arkajyoti Paul
- Drug DiscoveryGUSTO A Research GroupChittagongBangladesh
- Department of MicrobiologyJagannath UniversityDhakaBangladesh
| | - Talha Bin Emran
- Drug DiscoveryGUSTO A Research GroupChittagongBangladesh
- Department of PharmacyBGC Trust University BangladeshChittagongBangladesh
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Jurčić D, Gabrić M, Troskot Perić R, Liberati Pršo AM, Mirat J, Včev A, Alerić I, Ebling B. HERBALIFE® ASSOCIATED SEVERE HEPATOTOXICITY IN A PREVIOUSLY HEALTHY WOMAN. Acta Clin Croat 2019; 58:771-776. [PMID: 32595263 PMCID: PMC7314303 DOI: 10.20471/acc.2019.58.04.26] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Lately there has been an increased consumption of herbal preparations, distributed as nutritional supplements, often claimed to be ‘natural’ and harmless. However, as their use is not subjected to strict pre-marketing testing and regulations, their ingredients are not clearly defined and there is no quality control or proof of their effectiveness and safety. A growing body of references accentuate their harmful effects, in particular hepatotoxicity, which varies from minimal hepatogram changes to fulminant hepatitis requiring liver transplantation. This case report describes liver damage that was highly suspected to originate from Herbalife® products consumption. We excluded alcohol, viral, metabolic, autoimmune and neoplastic causes of liver lesions, as well as vascular liver disease, but we noticed a connection between the use of Herbalife® products and liver damage. The exact mechanism of liver damage in our patient was not determined. After removing the Herbalife® products, liver damage resolved and there was no need to perform liver biopsy. Taking into consideration the growing consumption of herbal products and their potential harmfulness, we consider that more strict regulations of their production process and sale are necessary, including exact identification of active substances with a list of ingredients, toxicologic testing and obligatory side effect report.
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Affiliation(s)
- Dragan Jurčić
- 1Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 2Department of Gastroenterology and Hepatology, Sveti Duh University Hospital, Zagreb, Croatia; 3Faculty of Health Studies, University of Rijeka, Rijeka, Croatia; 4Department of Endocrinology, Diabetes and Metabolic Diseases, Sveti Duh University Hospital, Zagreb, Croatia; 5Jordanovac Hospital for Lung Diseases, Zagreb University Hospital Centre, Zagreb, Croatia
| | - Maruška Gabrić
- 1Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 2Department of Gastroenterology and Hepatology, Sveti Duh University Hospital, Zagreb, Croatia; 3Faculty of Health Studies, University of Rijeka, Rijeka, Croatia; 4Department of Endocrinology, Diabetes and Metabolic Diseases, Sveti Duh University Hospital, Zagreb, Croatia; 5Jordanovac Hospital for Lung Diseases, Zagreb University Hospital Centre, Zagreb, Croatia
| | - Rosana Troskot Perić
- 1Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 2Department of Gastroenterology and Hepatology, Sveti Duh University Hospital, Zagreb, Croatia; 3Faculty of Health Studies, University of Rijeka, Rijeka, Croatia; 4Department of Endocrinology, Diabetes and Metabolic Diseases, Sveti Duh University Hospital, Zagreb, Croatia; 5Jordanovac Hospital for Lung Diseases, Zagreb University Hospital Centre, Zagreb, Croatia
| | - Ana Marija Liberati Pršo
- 1Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 2Department of Gastroenterology and Hepatology, Sveti Duh University Hospital, Zagreb, Croatia; 3Faculty of Health Studies, University of Rijeka, Rijeka, Croatia; 4Department of Endocrinology, Diabetes and Metabolic Diseases, Sveti Duh University Hospital, Zagreb, Croatia; 5Jordanovac Hospital for Lung Diseases, Zagreb University Hospital Centre, Zagreb, Croatia
| | - Jure Mirat
- 1Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 2Department of Gastroenterology and Hepatology, Sveti Duh University Hospital, Zagreb, Croatia; 3Faculty of Health Studies, University of Rijeka, Rijeka, Croatia; 4Department of Endocrinology, Diabetes and Metabolic Diseases, Sveti Duh University Hospital, Zagreb, Croatia; 5Jordanovac Hospital for Lung Diseases, Zagreb University Hospital Centre, Zagreb, Croatia
| | - Aleksandar Včev
- 1Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 2Department of Gastroenterology and Hepatology, Sveti Duh University Hospital, Zagreb, Croatia; 3Faculty of Health Studies, University of Rijeka, Rijeka, Croatia; 4Department of Endocrinology, Diabetes and Metabolic Diseases, Sveti Duh University Hospital, Zagreb, Croatia; 5Jordanovac Hospital for Lung Diseases, Zagreb University Hospital Centre, Zagreb, Croatia
| | - Ivan Alerić
- 1Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 2Department of Gastroenterology and Hepatology, Sveti Duh University Hospital, Zagreb, Croatia; 3Faculty of Health Studies, University of Rijeka, Rijeka, Croatia; 4Department of Endocrinology, Diabetes and Metabolic Diseases, Sveti Duh University Hospital, Zagreb, Croatia; 5Jordanovac Hospital for Lung Diseases, Zagreb University Hospital Centre, Zagreb, Croatia
| | - Barbara Ebling
- 1Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 2Department of Gastroenterology and Hepatology, Sveti Duh University Hospital, Zagreb, Croatia; 3Faculty of Health Studies, University of Rijeka, Rijeka, Croatia; 4Department of Endocrinology, Diabetes and Metabolic Diseases, Sveti Duh University Hospital, Zagreb, Croatia; 5Jordanovac Hospital for Lung Diseases, Zagreb University Hospital Centre, Zagreb, Croatia
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FERNANDES MDFL, MORAES SMD, SOUSA PHMD, MAGALHÃES CEDC, ALMEIDA MMB, SILVA MGDV. Characterization of leaves used in infusion preparation grown in northeastern Brazil by chemometric methods based on their multi-elemental composition. FOOD SCIENCE AND TECHNOLOGY 2019. [DOI: 10.1590/fst.00718] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Anderson N, Borlak J. Hepatobiliary Events in Migraine Therapy with Herbs-The Case of Petadolex, A Petasites Hybridus Extract. J Clin Med 2019; 8:jcm8050652. [PMID: 31083451 PMCID: PMC6572430 DOI: 10.3390/jcm8050652] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Revised: 04/29/2019] [Accepted: 05/03/2019] [Indexed: 12/28/2022] Open
Abstract
Petadolex®, a defined butterbur extract has clinically proven efficacy against migraine attacks. However, spontaneous reports indicate cases of herbal induced liver injury (HILI). While most HILI patients presented mild serum biochemistry changes (<3 ULN, dose range 50 to 225 mg/day; treatment duration 4–730 days) nine developed severe HILI (average time-to-onset 103 days, ALT-range 3–153; AST 2–104-fold ULN). HILI cases resolved after medication withdrawal though two patients required liver transplantation. Liver biopsies revealed an inconsistent injury pattern, i.e. necrosis, macrovesicular steatosis, inflammation, cholestasis, and bile duct proliferation. Causality assessment rated 3 cases likely, 13 possible, 8 unlikely and 24 as unclassifiable/unclassified. Note, 22 patients reported hepatotoxic co-medications especially during periods of pain. A no-observable-adverse-effect-level at 15-fold of the maximal clinical dose (3 mg/kg/day MCD) was established for rats. At >45 and 90-fold MCD bile duct hyperplasia was observed but could not be confirmed in an explorative minipig study at 218-fold MCD. Human hepatocyte studies at 49-fold Cmax serum petasins (=active ingredient) and therapeutic Ibuprofen, Paracetamol and Naratriptan concentrations evidenced liver transaminase and CYP-monooxygenase changes. Collectively, Petadolex® HILI cases are rare, idiosyncratic and frequently confounded by co-medications. A physician-supervised self-medication plan with herbs and pain relief medication is needed to minimize risk for HILI.
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Affiliation(s)
- Nora Anderson
- Hannover Medical School, Centre for Pharmacology and Toxicology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
| | - Jürgen Borlak
- Hannover Medical School, Centre for Pharmacology and Toxicology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
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Histological, Biochemical, and Hematological Effects of Goniothalamin on Selective Internal Organs of Male Sprague-Dawley Rats. J Toxicol 2019; 2019:6493286. [PMID: 31178909 PMCID: PMC6507267 DOI: 10.1155/2019/6493286] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2018] [Accepted: 01/15/2019] [Indexed: 02/06/2023] Open
Abstract
Goniothalamin (GTN) is an isolated compound from several plants of the genus Goniothalamus, and its anticancer effect against several cancers was reported. However, there is no scientific data about effects of its higher doses on internal organs. Accordingly, this study aimed to evaluate the acute and subacute effects of higher doses of GTN on the hematology, biochemistry, and histology of selected internal organs of male Sprague-Dawley rats. In acute study, 35 rats were distributed in 5 groups (n=7) which were intraperitoneally (IP) injected with a single dose of either 100, 200, 300, 400, or 500 mg/kg of GTN, while extra 7 rats serve as a normal control. In subacute study, 7 rats were IP-injected with a daily dose of 42 mg/kg of GTN for 14 days, while another 7 rats serve as a normal control group. The normal controls in both studies were IP-injected simultaneously with 2 ml/kg of 10% DMSO in PBS. At the end of both tests, rats were sacrificed to collect blood for hematology and biochemistry and harvest livers, kidneys, lungs, hearts, spleens, and brains for histology. During acute and subacute exposure, no abnormal changes were observed in the hematology, biochemistry, and histology of the internal organs. However, the 300, 400, and 500 mg/kg of GTN during acute exposure were associated with morbidities and mortalities. Ultimately, GTN could be safe up to the dose of 200 mg/kg, and the dose of 42 mg/kg of GTN was tolerated well.
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31
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Sun Y, Shi S, Li Y, Wang Q. Development of quantitative structure-activity relationship models to predict potential nephrotoxic ingredients in traditional Chinese medicines. Food Chem Toxicol 2019; 128:163-170. [PMID: 30954639 DOI: 10.1016/j.fct.2019.03.056] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Revised: 03/26/2019] [Accepted: 03/31/2019] [Indexed: 12/13/2022]
Abstract
The broad use of traditional Chinese medicines (TCMs) and the accompanied incidences of kidney injury have attracted considerable interest in investigating the responsible toxic ingredients. It is challenging to evaluate toxicity of TCMs since they contain complex mixtures of phytochemicals. Quantitative structure-activity relationship (QSAR) is an efficient tool to predict toxicity and QSAR study on TCMs-induced nephrotoxicity remains lacked. We developed QSAR models using three datasets of 609 compounds: natural products, drugs, and mixed (contained both kinds of data) datasets. Each dataset was used for modelling by utilizing artificial neural networks (ANN) and support vector machines (SVM) algorithms separately. Both internal and external validations were performed on each model. Six QSAR models were developed and yielded reliable performance in the internal validation. For external validation, 30 ingredients in the TCMs were predicted well by the natural product models (accuracy: ANN 96.7%, SVM 93.3%). The mixed models (accuracy: ANN 76.7%, SVM 66.7%) showed a better performance than the drug models (accuracy: ANN 50%, SVM 53.3%). Particularly, natural product models produced the most reliable results. It has the application not only on screening the nephrotoxic ingredients in TCMs, but it is also helpful at prioritizing the subsequent toxicity testing of natural products.
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Affiliation(s)
- Yuqing Sun
- Department of Toxicology, School of Public Health, Peking University, Beijing, 100191, China; Key Laboratory of State Administration of Traditional Chinese Medicine for Compatibility Toxicology, Beijing, 100191, China
| | - Shaoze Shi
- Department of Toxicology, School of Public Health, Peking University, Beijing, 100191, China; Key Laboratory of State Administration of Traditional Chinese Medicine for Compatibility Toxicology, Beijing, 100191, China
| | - Yaqiu Li
- Department of Toxicology, School of Public Health, Peking University, Beijing, 100191, China; Key Laboratory of State Administration of Traditional Chinese Medicine for Compatibility Toxicology, Beijing, 100191, China
| | - Qi Wang
- Department of Toxicology, School of Public Health, Peking University, Beijing, 100191, China; Key Laboratory of State Administration of Traditional Chinese Medicine for Compatibility Toxicology, Beijing, 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, China.
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Zhang L, Wang T, Zhao BS, Zhang JX, Yang S, Fan CL, Li P. Effect of 2″- O-Rhamnosyl Icariside II, Baohuoside I and Baohuoside II in Herba Epimedii on Cytotoxicity Indices in HL-7702 and HepG2 Cells. Molecules 2019; 24:molecules24071263. [PMID: 30939785 PMCID: PMC6479309 DOI: 10.3390/molecules24071263] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Revised: 03/29/2019] [Accepted: 03/30/2019] [Indexed: 01/14/2023] Open
Abstract
Herba Epimedii, a commonly used Chinese medicine, has attracted much attention recently because of its potential hepatotoxic effects. 2″-O-Rhamnosyl icariside II, baohuoside I and baohuoside II are the main components of Herba Epimedii, and previous research indicates that these three compounds are related to the hepatotoxicity of Herba Epimedii. To test this idea, in this study, HL-7702 and HepG2 cells were chosen as the in vitro models and the influences of these three compounds on a series of cytotoxicity indices, including ALT, AST, LDH, SOD, GSH, MDA, ROS and MMP, were determined. The results showed that at certain concentrations, the three compounds had different effects on the indices. Among them, baohuoside I at high concentration (32 μg/mL) displayed more significant cytotoxicity than the other two compounds; therefore, it was inferred to be more closely correlated with the liver injury induced by Herba Epimedii combined with the previous study, and its toxic mechanisms may be involved in increasing oxidative stress and inducing apoptosis. The findings of this study may provide evidence of the toxic composition of Herba Epimedii to preliminarily discuss the toxic mechanisms and provide improved guidance for its clinical safety.
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Affiliation(s)
- Lin Zhang
- Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Chaoyang District, Beijing 10029, China.
| | - Ting Wang
- Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Chaoyang District, Beijing 10029, China.
| | - Bao-Sheng Zhao
- Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Chaoyang District, Beijing 10029, China.
| | - Jing-Xuan Zhang
- Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Chaoyang District, Beijing 10029, China.
| | - Song Yang
- Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Chaoyang District, Beijing 10029, China.
| | - Chun-Lan Fan
- Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Chaoyang District, Beijing 10029, China.
| | - Pin Li
- Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Chaoyang District, Beijing 10029, China.
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Zhu J, Seo JE, Wang S, Ashby K, Ballard R, Yu D, Ning B, Agarwal R, Borlak J, Tong W, Chen M. The Development of a Database for Herbal and Dietary Supplement Induced Liver Toxicity. Int J Mol Sci 2018; 19:E2955. [PMID: 30274144 PMCID: PMC6213387 DOI: 10.3390/ijms19102955] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Revised: 09/10/2018] [Accepted: 09/21/2018] [Indexed: 12/14/2022] Open
Abstract
The growing use of herbal dietary supplements (HDS) in the United States provides compelling evidence for risk of herbal-induced liver injury (HILI). Information on HDS products was retrieved from MedlinePlus of the U.S. National Library of Medicine and the herbal monograph of the European Medicines Agency. The hepatotoxic potential of HDS was ascertained by considering published case reports. Other relevant data were collected from governmental documents, public databases, web sources, and the literature. We collected information for 296 unique HDS products. Evidence of hepatotoxicity was reported for 67, that is 1 in 5, of these HDS products. The database revealed an apparent gender preponderance with women representing 61% of HILI cases. Culprit hepatotoxic HDS were mostly used for weight control, followed by pain and inflammation, mental stress, and mood disorders. Commonly discussed mechanistic events associated with HILI are reactive metabolites and oxidative stress, mitochondrial injury, as well as inhibition of transporters. HDS⁻drug interactions, causing both synergistic and antagonizing effects of drugs, were also reported for certain HDS. The database contains information for nearly 300 commonly used HDS products to provide a single-entry point for better comprehension of their impact on public health.
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Affiliation(s)
- Jieqiang Zhu
- Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
| | - Ji-Eun Seo
- Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
| | - Sanlong Wang
- Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
- National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, China's State Food and Drug Administration, Beijing 100176, China.
| | - Kristin Ashby
- Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
| | - Rodney Ballard
- Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
| | - Dianke Yu
- Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
| | - Baitang Ning
- Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
| | - Rajiv Agarwal
- Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
| | - Jürgen Borlak
- Center of Pharmacology and Toxicology, Hannover Medical School, 30625 Hannover, Germany.
| | - Weida Tong
- Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
| | - Minjun Chen
- Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.
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Yalcin S, Hurmuz P, McQuinn L, Naing A. Prevalence of Complementary Medicine Use in Patients With Cancer: A Turkish Comprehensive Cancer Center Experience. J Glob Oncol 2018; 4:1-6. [PMID: 30241173 PMCID: PMC6180833 DOI: 10.1200/jgo.2016.008896] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
PURPOSE Complementary and alternative medicine (CAM) has been popular among patients with cancer for several decades. The objectives of this study were to evaluate the prevalence of CAM use and to identify the factors affecting CAM use in a large patient cohort seen at a comprehensive cancer center in Turkey. PATIENTS AND METHODS An investigator-designed survey was completed by volunteer patients who visited the outpatient clinic in the medical oncology department. CAM use encompassed pharmacologic agents including vitamins, dietary supplements, and herbal products or nonpharmacologic methods like prayer, meditation, hypnosis, massage, or acupuncture. RESULTS Of 1,499 patients who answered the survey, 1,433 (96%) used nonpharmacologic CAM and 60 (4%) used pharmacologic CAM (pCAM). The most frequent types of CAM used were prayer (n = 1,433) followed by herbal products (n = 42). pCAM use was not significantly associated with age ( P = .63), sex ( P = .15), diagnosis ( P = .15), or income level ( P = .09). However, it was significantly associated with the level of education ( P = .0067) and employment status ( P < .001). Patients with higher education levels used more pCAM products ( P = .025). Among 60 pCAM users, six patients (10%) used pCAM for more than 2 years and 22 (36%) did not consult their physicians about their pCAM use. Only nine patients (15%) reported unpleasant adverse effects related to pCAM. CONCLUSION Although CAM use was high among our patients, prevalence of pCAM use was lower than expected. Patients with higher education levels tended to use more pCAM.
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Affiliation(s)
- Suayib Yalcin
- Suayib Yalcin and Pervin Hurmuz, Hacettepe
University School of Medicine, Ankara, Turkey; and Lacey McQuinn
and Aung Naing, University of Texas MD Anderson Cancer Center,
Houston, TX
| | - Pervin Hurmuz
- Suayib Yalcin and Pervin Hurmuz, Hacettepe
University School of Medicine, Ankara, Turkey; and Lacey McQuinn
and Aung Naing, University of Texas MD Anderson Cancer Center,
Houston, TX
| | - Lacey McQuinn
- Suayib Yalcin and Pervin Hurmuz, Hacettepe
University School of Medicine, Ankara, Turkey; and Lacey McQuinn
and Aung Naing, University of Texas MD Anderson Cancer Center,
Houston, TX
| | - Aung Naing
- Suayib Yalcin and Pervin Hurmuz, Hacettepe
University School of Medicine, Ankara, Turkey; and Lacey McQuinn
and Aung Naing, University of Texas MD Anderson Cancer Center,
Houston, TX
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35
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Amadi CN, Orisakwe OE. Herb-Induced Liver Injuries in Developing Nations: An Update. TOXICS 2018; 6:toxics6020024. [PMID: 29673137 PMCID: PMC6027193 DOI: 10.3390/toxics6020024] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Revised: 04/03/2018] [Accepted: 04/14/2018] [Indexed: 12/16/2022]
Abstract
The last few decades have seen a rise in the use of herbal supplements, natural products, and traditional medicines. However, there are growing concerns related to the safety and toxicities of these medicines. These herbal medicines are associated with complications such as liver damage with a high incidence of mortalities and morbidities. Clinical manifestations range from asymptomatic cases with abnormal liver functions tests to sudden and severe liver failure necessitating liver transplantation. This work aimed to review the etiology, risk factors, diagnosis, clinical manifestations and selected clinical case reports of herbal hepatotoxicity in developing nations. PubMed and Google Scholar searches were undertaken to identify relevant literature. Furthermore, we scanned the reference lists of the primary and review articles to identify publications not retrieved by electronic searches. Little data exists on clinical cases of herb-induced liver injury in some developing countries such as Nigeria, as most incidences are either not reported to health care providers or reports from hospitals go unpublished. Studies in Nigeria have highlighted a possible correlation between use of herbs and liver disease. In Uganda, and association between the use of traditional herbal medicine with liver fibrosis in HIV-infected and non-HIV patients was demonstrated. Reports from China have revealed incidences of acute liver failure as a result of herbal medicine use. The actual incidence and prevalence of HILI in developing nations remain largely unknown due to both poor pharmacovigilance programs and non-application of emerging technologies. Improving education and public awareness of the potential risks of herbals and herbal products is desirable to ensure that suspected adverse effects are formally reported. There is need for stricter regulations and pre-clinical studies necessary for efficacy and safety.
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Affiliation(s)
- Cecilia Nwadiuto Amadi
- Department of Experimental Pharmacology & Toxicology, Faculty of Pharmacy, University of Port-Harcourt, PMB, 5323 Port Harcourt, Rivers State, Nigeria.
| | - Orish Ebere Orisakwe
- Department of Experimental Pharmacology & Toxicology, Faculty of Pharmacy, University of Port-Harcourt, PMB, 5323 Port Harcourt, Rivers State, Nigeria.
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36
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Abby Philips C, Augustine P. Herbal tea consumption and the liver - All is not what it seems! J Hepatol 2018; 68:612-613. [PMID: 28987519 DOI: 10.1016/j.jhep.2017.08.037] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Accepted: 08/22/2017] [Indexed: 01/23/2023]
Affiliation(s)
- Cyriac Abby Philips
- The Liver Unit, Cochin Gastroenterology Group, Ernakulam Medical Centre, Cochin, Kerala 682028, India.
| | - Philip Augustine
- The Liver Unit, Cochin Gastroenterology Group, Ernakulam Medical Centre, Cochin, Kerala 682028, India
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Alferink LJM, Kiefte-de Jong JC, Darwish Murad S. Reply to: "Herbal tea consumption and the liver - All is not what is seems!". J Hepatol 2018; 68:613-614. [PMID: 28986102 DOI: 10.1016/j.jhep.2017.09.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2017] [Accepted: 09/24/2017] [Indexed: 12/29/2022]
Affiliation(s)
- Louise J M Alferink
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Jessica C Kiefte-de Jong
- Department of Epidemiology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands; Leiden University College, The Hague, The Netherlands
| | - Sarwa Darwish Murad
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands.
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Abstract
In October 2015, the drug-induced liver diseases group of the Chinese Society of Hepatology drafted and published the first Diagnosis and Treatment Guidelines on Drug-induced Liver Injury in China, giving suggestions on the diagnosis and treatment of drug-induced liver injury (DILI). As a psychiatrist, I have found that in clinical practice both typical and new antipsychotic drugs can induce liver injury to varying degrees. Therefore, it is necessary to quickly and accurately determine the cause of liver injury and the type and severity of injury and establish a solution. This article reviewed relevant literature including the common pathogenesis and clinical manifestations of drug-induced liver injury caused by antipsychotic drugs, laboratory tests, diagnostic criteria and classification, and clinical management strategies. This paper also includes a summary and a perspective on liver injury caused by antipsychotic drugs.
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Affiliation(s)
- Qinyu Lv
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhenghui Yi
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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39
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Byard RW, Musgrave I, Maker G, Bunce M. What risks do herbal products pose to the Australian community? Med J Aust 2017; 206:86-90. [PMID: 28152355 DOI: 10.5694/mja16.00614] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2016] [Accepted: 08/15/2016] [Indexed: 11/17/2022]
Abstract
Traditional herbal products are widely used in Australia to treat a broad range of conditions and diseases. It is popularly believed that these products are safer than prescribed drugs. While many may be safe, it is worrying that the specific effects and harmful interactions of a number of their components with prescription medications is not well understood. Some traditional herbal preparations contain heavy metals and toxic chemicals, as well as naturally occurring organic toxins. The effects of these substances can be dire, including acute hepatic and renal failure, exacerbation of pre-existing conditions and diseases, and even death. The content and quality of herbal preparations are not tightly controlled, with some ingredients either not listed or their concentrations recorded inaccurately on websites or labels. Herbal products may also include illegal ingredients, such as ephedra, Asarum europaeum (European wild ginger) and endangered animal species (eg, snow leopard). An additional problem is augmentation with prescription medications to enhance the apparent effectiveness of a preparation. Toxic substances may also be deliberately or inadvertently added: less expensive, more harmful plants may be substituted for more expensive ingredients, and processing may not be adequate. The lack of regulation and monitoring of traditional herbal preparations in Australia and other Western countries means that their contribution to illness and death is unknown. We need to raise awareness of these problems with health care practitioners and with the general public.
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Affiliation(s)
| | | | | | - Michael Bunce
- Trace and Environmental DNA Laboratory (TrEnD), Curtin University, Perth, WA
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40
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Ali M, Khan T, Fatima K, Ali QUA, Ovais M, Khalil AT, Ullah I, Raza A, Shinwari ZK, Idrees M. Selected hepatoprotective herbal medicines: Evidence from ethnomedicinal applications, animal models, and possible mechanism of actions. Phytother Res 2017; 32:199-215. [PMID: 29047177 PMCID: PMC7167792 DOI: 10.1002/ptr.5957] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Revised: 08/30/2017] [Accepted: 09/26/2017] [Indexed: 02/06/2023]
Abstract
Insight into the hepatoprotective effects of medicinally important plants is important, both for physicians and researchers. Main reasons for the use of herbal medicine include their lesser cost compared with conventional drugs, lesser undesirable drug reactions and thus high safety, and reduced side effects. The present review focuses on the composition, pharmacology, and results of experimental trials of selected medicinal plants: Silybum marianum (L.) Gaertn., Glycyrrhiza glabra, Phyllanthus amarus Schumach. & Thonn., Salvia miltiorrhiza Bunge., Astragalus membranaceus (Fisch.) Bunge, Capparis spinosa (L.), Cichorium intybus (L.), Solanum nigrum (L.), Sapindus mukorossi Gaertn., Ginkgo biloba (L.), Woodfordia fruticosa (L.) Kurz, Vitex trifolia (L.), Schisandra chinensis (Turcz.) Baill., Cuscuta chinensis (Lam.), Lycium barbarum, Angelica sinensis (Oliv.) Diels, and Litsea coreana (H. Lev.). The probable modes of action of these plants include immunomodulation, stimulation of hepatic DNA synthesis, simulation of superoxide dismutase and glutathione reductase to inhibit oxidation in hepatocytes, reduction of intracellular reactive oxygen species by enhancing levels of antioxidants, suppression of ethanol-induced lipid accumulation, inhibition of nucleic acid polymerases to downregulate viral mRNA transcription and translation, free radical scavenging and reduction of hepatic fibrosis by decreasing the levels of transforming growth factor beta-1, and collagen synthesis in hepatic cells. However, further research is needed to identify, characterize, and standardize the active ingredients, useful compounds, and their preparations for the treatment of liver diseases.
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Affiliation(s)
- Muhammad Ali
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Tariq Khan
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan.,Department of Biotechnology, University of Malakand Chakdara Dir (L)-18000, Khyber Pakhtunkhwa, Pakistan
| | - Kaneez Fatima
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Qurat Ul Ain Ali
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Muhammad Ovais
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Ali Talha Khalil
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Ikram Ullah
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Abida Raza
- National Institute of Laser and Optronics, Nilore, 45650, Pakistan
| | - Zabta Khan Shinwari
- Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad, 45320, Pakistan
| | - Muhammad Idrees
- Hazara University Mansehra, Khyber Pakhtunkhwa, 21120, Pakistan.,Center for Applied Molecular Biology (CAMB), University of the Punjab, Lahore, 53700, Pakistan
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Xu Y, Niu Y, Gao Y, Wang F, Qin W, Lu Y, Hu J, Peng L, Liu J, Xiong W. Borapetoside E, a Clerodane Diterpenoid Extracted from Tinospora crispa, Improves Hyperglycemia and Hyperlipidemia in High-Fat-Diet-Induced Type 2 Diabetes Mice. JOURNAL OF NATURAL PRODUCTS 2017; 80:2319-2327. [PMID: 28742368 DOI: 10.1021/acs.jnatprod.7b00365] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
An insidious increase in the incidence of obesity, insulin resistance, and hyperlipidemia has led to an epidemic of type 2 diabetes worldwide. Tinospora crispa (T. crispa) is a familiar plant traditionally used in herbal medicine for diabetes; however, the major active ingredients of this plant are still unclear. In this study, we identified the therapeutic effects of borapetoside E, a small molecule extracted from T. crispa, in high-fat-diet (HFD)-induced obesity in mice. The therapeutic effects of borapetoside E in HFD-induced obese mice were assessed physiologically, histologically, and biochemically following intraperitoneal injection. Furthermore, we analyzed the expression of glucose and lipid metabolism-related genes and proteins in borapetoside E-treated obese mice. Compared with vehicle-treated mice, borapetoside E markedly improved hyperglycemia, insulin resistance, hepatic steatosis, hyperlipidemia, and oxygen consumption in obese mice, and the effects were comparable to or better than the drug metformin. In addition, borapetoside E suppressed the expression of sterol regulatory element binding proteins (SREBPs) and their downstream target genes related to lipid synthesis in the liver and adipose tissue. Borapetoside E showed beneficial effects in vivo, demonstrating that borapetoside E may be a potential therapy for the treatment of diet-induced type 2 diabetes and related metabolic syndromes.
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Affiliation(s)
- Yuhui Xu
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201, People's Republic of China
- University of the Chinese Academy of Sciences , Beijing 100049, People's Republic of China
| | - Yanfen Niu
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201, People's Republic of China
- University of the Chinese Academy of Sciences , Beijing 100049, People's Republic of China
- Engineering Research Center, Kunming Medical University , Kunming 650500, People's Republic of China
| | - Yuan Gao
- BioBioPha Co., Ltd , Kunming 650201, People's Republic of China
- Deparment of Chemical Engineering, Yibin University , Yibin 644000, People's Republic of China
| | - Fang Wang
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201, People's Republic of China
- University of the Chinese Academy of Sciences , Beijing 100049, People's Republic of China
| | - Wanying Qin
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201, People's Republic of China
- University of the Chinese Academy of Sciences , Beijing 100049, People's Republic of China
| | - Yanting Lu
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201, People's Republic of China
- University of the Chinese Academy of Sciences , Beijing 100049, People's Republic of China
| | - Jing Hu
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201, People's Republic of China
- University of the Chinese Academy of Sciences , Beijing 100049, People's Republic of China
| | - Li Peng
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201, People's Republic of China
- University of the Chinese Academy of Sciences , Beijing 100049, People's Republic of China
| | - Jikai Liu
- School of Pharmaceutical Sciences, South-Central University for Nationalities , Wuhan 430074, People's Republic of China
| | - Wenyong Xiong
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences , Kunming 650201, People's Republic of China
- University of the Chinese Academy of Sciences , Beijing 100049, People's Republic of China
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42
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Bernardini S, Tiezzi A, Laghezza Masci V, Ovidi E. Natural products for human health: an historical overview of the drug discovery approaches. Nat Prod Res 2017; 32:1926-1950. [DOI: 10.1080/14786419.2017.1356838] [Citation(s) in RCA: 96] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Affiliation(s)
- S. Bernardini
- Laboratory of Plant Cytology and Biotechnology, Department for the Innovation in Biological, Agrofood and Forestal Systems (DIBAF), Tuscia University, Viterbo, Italy
| | - A. Tiezzi
- Laboratory of Plant Cytology and Biotechnology, Department for the Innovation in Biological, Agrofood and Forestal Systems (DIBAF), Tuscia University, Viterbo, Italy
| | - V. Laghezza Masci
- Laboratory of Plant Cytology and Biotechnology, Department for the Innovation in Biological, Agrofood and Forestal Systems (DIBAF), Tuscia University, Viterbo, Italy
| | - E. Ovidi
- Laboratory of Plant Cytology and Biotechnology, Department for the Innovation in Biological, Agrofood and Forestal Systems (DIBAF), Tuscia University, Viterbo, Italy
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43
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Yoshikawa K, Kawashima R, Hirose Y, Shibata K, Akasu T, Hagiwara N, Yokota T, Imai N, Iwaku A, Kobayashi G, Kobayashi H, Kinoshita A, Fushiya N, Kijima H, Koike K, Saruta M. Liver injury after aluminum potassium sulfate and tannic acid treatment of hemorrhoids. World J Gastroenterol 2017; 23:5034-5040. [PMID: 28785156 PMCID: PMC5526772 DOI: 10.3748/wjg.v23.i27.5034] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2017] [Revised: 06/09/2017] [Accepted: 06/19/2017] [Indexed: 02/06/2023] Open
Abstract
We are reporting a rare case of acute liver injury that developed after an internal hemorrhoid treatment with the aluminum potassium sulfate and tannic acid (ALTA) regimen. A 41-year-old man developed a fever and liver injury after undergoing internal hemorrhoid treatment with a submucosal injection of ALTA with lidocaine. The acute liver injury was classified clinically as hepatocellular and pathologically as cholestastic. We could not classify the mechanism of injury. High eosinophil and immunoglobulin E levels characterized the injury, and a drug lymphocyte stimulation test was negative on postoperative day 25. Fluid replacement for two weeks after hospitalization improved the liver injury. ALTA therapy involves injecting chemicals into the submucosa, from the rectum to the anus, and this is the first description of a case that developed a severe liver disorder after this treatment; hence, an analysis of future cases as they accumulate is desirable.
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Li ZJ, Abulizi A, Zhao GL, Wang T, Zhou F, Jiang ZZ, Aibai S, Zhang LY. Bakuchiol Contributes to the Hepatotoxicity of Psoralea corylifolia in Rats. Phytother Res 2017. [PMID: 28639266 DOI: 10.1002/ptr.5851] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Psoralea corylifolia L. (Fructus Psoraleae) is widely used in Asia, but there are concerns about hepatotoxicity caused by constituents such as psoralens and bakukiol. Bakuchiol (BAK) has antiinflammatory, antipyretic, antibacterial antiviral, anticancer, and estrogenic activity but appears to be hepatotoxic in in vitro tests. This study investigated the hepatotoxicity in vivo in rats. Using intragastrically administered bakuchiol at doses of 52.5 and 262.5 mg/kg for 6 weeks. Bodyweight, relative liver weight, biochemical indicators, histopathology, mRNA expression of CYP7A1, HMG-CoA reductase, BSEP, PPARα, SREBP-2, and MRP3 were measured. Many abnormalities were observed in the bakuchiol-treated groups including suppression of weight gain and food intake, change of some parameters in serum biochemistry, and increased weight of liver. The mRNA expression of CYP7A1, HMG-CoA reductase, PPARα, and SREBP-2 decreased in bakuchiol-treated group, the expression of BSEP increased in bakuchiol-treated low dosage, and the expression of BSEP decreased in bakuchiol-treated high dosage. In conclusion, we provide evidence for the first time that bakuchiol can induce cholestatic hepatotoxicity, suggesting potential hepatotoxicity. The mechanism may be related to effects on liver lipid metabolism, but further investigation is necessary. Copyright © 2017 John Wiley & Sons, Ltd.
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Affiliation(s)
- Zhi-Jian Li
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China.,Department of Toxicology Laboratory Xinjiang Institute of Traditional Uyghur Medicine, Xinjiang Laboratory of Uyghur Medical Prescription, Urumqi, Xinjiang, 830049, China
| | - Abudumijiti Abulizi
- Basic Medical College, Xinjiang Medical University, Xinjiang Uyghur Autonomous Region, Urumqi, 830054, China
| | - Guo-Lin Zhao
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China
| | - Tao Wang
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China
| | - Fan Zhou
- Xinjiang Huashidan Pharmaceutical Research Co., Ltd, Urumqi, Xinjiang, 830011, China
| | - Zhen-Zhou Jiang
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China
| | - Silafu Aibai
- Department of Toxicology Laboratory Xinjiang Institute of Traditional Uyghur Medicine, Xinjiang Laboratory of Uyghur Medical Prescription, Urumqi, Xinjiang, 830049, China
| | - Lu-Yong Zhang
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China
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45
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Shabat Y, Ilan Y. A synergistic effect of Cremophor and beta glucosylceramide to exert liver and sugar protection. JOURNAL OF FOOD SCIENCE AND TECHNOLOGY 2017; 54:1184-1191. [PMID: 28416868 DOI: 10.1007/s13197-017-2520-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Revised: 12/15/2016] [Accepted: 01/31/2017] [Indexed: 12/29/2022]
Abstract
Many commonly used drugs carry the potential to induce hepatotoxicity, and a large number of foods and beverages induce an increase in blood sugar levels. A change in lifestyle by omitting these compounds is not applicable in many circumstances. β-Glucosylceramide (GC) is a naturally occurring glycosphingolipid that exerts an effect on the immune system. Cremophor EL (CrEL) is a synthetic, nonionic surfactant that is used as a vehicle for the administration of water-insoluble compounds. The aim of the present study was to determine the synergistic effect of oral administration of the combination of GC and CrEL (GCC) when added to potential toxic substrates or to sugar-enriched compounds. Four groups of mice, treated with PBS, GC, CrEL, or GCC were studied in the concanavalin A immune-mediated hepatitis model, in the acetaminophen (APAP) toxicity model, and as additives to two types of sugar-enriched soda drinks. Both GC and CrEL exerted hepatoprotective effects in the ConA hepatitis and APAP toxicity models. Moreover, in both models, GCC exerted a synergistic effect in ameliorating liver damage as manifested by a significant decrease in the ALT serum levels. When added to two types of sugar-enriched sodas, GCC exerted a synergistic effect in ameliorating the increase in blood sugar levels. GCC exerts synergistic hepatoprotective and glucose-protective effects in models of liver damage and increased serum glucose. GCC can provide liver and sugar protection when co-administered with hepatotoxic drugs or sugar-enriched drinks.
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Affiliation(s)
- Yehudit Shabat
- Gastroenterology and Liver Units, Department of Medicine, Hadassah-Hebrew University Medical Center, POB 1200, 91120 Ein-Kerem, Jerusalem, Israel
| | - Yaron Ilan
- Gastroenterology and Liver Units, Department of Medicine, Hadassah-Hebrew University Medical Center, POB 1200, 91120 Ein-Kerem, Jerusalem, Israel
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Letsyo E, Jerz G, Winterhalter P, Beuerle T. Toxic pyrrolizidine alkaloids in herbal medicines commonly used in Ghana. JOURNAL OF ETHNOPHARMACOLOGY 2017; 202:154-161. [PMID: 28284793 DOI: 10.1016/j.jep.2017.03.008] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Revised: 03/06/2017] [Accepted: 03/07/2017] [Indexed: 06/06/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Herbal medicines have been used for centuries for the management and treatment of various ailments due to the belief that they pose only little or no health risk and side effects, and also, in part, due to their availability, affordability and/or self-supply. However, the increasing information over the recent years on the occurrence of pyrrolizidine alkaloids (PAs) in honey, herbal food and tea products has raised concerns about the safety of herbal medicines with respect to contamination. To this day, little is known on the occurrence of toxic PAs in herbal medicines, especially in tropical West Africa. The aim of this study was therefore to determine the PA content of 70 well-known and widely patronized plant-derived medicinal preparations, which are commercialized in Ghana and some West African countries, in order to ascertain their potential health risk. MATERIALS AND METHODS PAs of the herbal medicinal products, sourced from specialized drugstores and mostly regulatory approved, were analyzed for their PA content by a HPLC-ESI-MS/MS sum parameter method. RESULTS The results show that a total of 60% of the analyzed herbal products were PA positive, indicating an average PA-concentration of 25.0μg/kg. The maximum PA level (1290.0μg/kg) was attributed to a regulatory-approved herbal medicine not known, according to the list of declared ingredients, to contain PA-plant parts. Interestingly, higher PA content (average, 30.2μg/kg) was detected in regulatory-approved herbal medicines, in contrast to lower amount (average, 8.0μg/kg) detected in non-regulatory-approved products. CONCLUSION The findings of this study clearly demonstrate that herbal medicines containing PA plants as ingredients, as well as some of those containing plant species not known to produce PAs, are likely to contain hepatotoxic PA at levels higher than the daily dose in food and herbal medicinal products proposed by the European Medicines Agency (i.e. 0.35μg PA per day for 50kg adult and 0.14μg PA per day for 20kg children). Hence, regulatory authorities are advised to carry out more rigorous quality control tests with respect to PAs so as to minimize the exposure of the consumers to these toxic compounds.
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Affiliation(s)
- Emmanuel Letsyo
- Institut für Lebensmittelchemie, Technische Universität Braunschweig, Schleinitzstrasse 20, 38106 Braunschweig, Germany
| | - Gerold Jerz
- Institut für Lebensmittelchemie, Technische Universität Braunschweig, Schleinitzstrasse 20, 38106 Braunschweig, Germany
| | - Peter Winterhalter
- Institut für Lebensmittelchemie, Technische Universität Braunschweig, Schleinitzstrasse 20, 38106 Braunschweig, Germany
| | - Till Beuerle
- Institut für Pharmazeutische Biologie, Technische Universität Braunschweig, Mendelssohnstrasse 1, 38106 Braunschweig, Germany.
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Screening for main components associated with the idiosyncratic hepatotoxicity of a tonic herb, Polygonum multiflorum. Front Med 2017; 11:253-265. [PMID: 28315126 DOI: 10.1007/s11684-017-0508-9] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2016] [Accepted: 11/24/2016] [Indexed: 01/30/2023]
Abstract
The main constituents of a typical medicinal herb, Polygonum multiflorum (Heshouwu in Chinese), that induces idiosyncratic liver injury remain unclear. Our previous work has shown that cotreatment with a nontoxic dose of lipopolysaccharide (LPS) and therapeutic dose of Heshouwu can induce liver injury in rats, whereas the solo treatment cannot induce observable injury. In the present work, using the constituent "knock-out" and "knock-in" strategy, we found that the ethyl acetate (EA) extract of Heshouwu displayed comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats. Results indicated a significant elevation of plasma alanine aminotransferase, aspartate aminotransferase, and liver histologic changes, whereas other separated fractions failed to induce liver injury. The mixture of EA extract with other separated fractions induced comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats. Chemical analysis further revealed that 2,3,5,4'-tetrahydroxy trans-stilbene-2-O-β-glucoside (trans-SG) and its cis-isomer were the two major compounds in EA extract. Furthermore, the isolated cis-, and not its trans-isomer, displayed comparable idiosyncratic hepatotoxicity to EA extract in LPS-treated rats. Higher contents of cis-SG were detected in Heshouwu liquor or preparations from actual liver intoxication patients associated with Heshouwu compared with general collected samples. In addition, plasma metabolomics analysis showed that cis-SG-disturbing enriched pathways remarkably differed from trans-SG ones in LPS-treated rats. All these results suggested that cis-SG was closely associated with the idiosyncratic hepatotoxicity of Heshouwu. Considering that the cis-trans isomerization of trans-SG was mediated by ultraviolet light or sunlight, our findings serve as reference for controlling photoisomerization in drug discovery and for the clinical use of Heshouwu and stilbene-related medications.
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Hepatotoxicity due to red bush tea consumption: a case report. J Clin Anesth 2016; 35:96-98. [DOI: 10.1016/j.jclinane.2016.07.027] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Revised: 06/09/2016] [Accepted: 07/14/2016] [Indexed: 11/18/2022]
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Brown AC. Liver toxicity related to herbs and dietary supplements: Online table of case reports. Part 2 of 5 series. Food Chem Toxicol 2016; 107:472-501. [PMID: 27402097 DOI: 10.1016/j.fct.2016.07.001] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2016] [Revised: 06/30/2016] [Accepted: 07/01/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND No online current list of potentially life-threatening, hepatotoxic herbs and dietary supplements based on PubMed case reports exists in a summarized tabular form. METHODS Documented case reports of herbs or dietary supplements (DS; includes herbs) appearing to contribute to liver injury were used to create an online "DS Toxic Table" of potentially hepatotoxic herbs and dietary supplements (PubMed, 1966 to June, 2016, and cross-referencing). The spectrum of DS induced liver injuries (DSILI) included elevated liver enzymes, hepatitis, steatosis, cholestasis, hepatic necrosis, hepatic fibrosis, hepatic cirrhosis, veno-occlusive disease, acute liver failure requiring a liver transplant, and death. RESULTS Over the past 50 years, approximately 21 herbs (minus germander and usnic acid that are no longer sold) and 12 dietary supplements (minus the nine no longer sold and vitamin A & niacin due to excess intake) posed a possible risk for liver injures in certain individuals. The herbs with the most number of reported publications (but not cases studies) in descending order, were germander, black cohosh, kava extract, and green tea extract. CONCLUSION These online DS Toxic Tables will contribute to continued Phase IV post marketing surveillance to detect possible liver toxicity cases and serve to forewarn consumers, clinicians, and corporations.
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Affiliation(s)
- Amy Christine Brown
- Department of Complementary and Alternative Medicine, John A. Burns School of Medicine, 651 Ilalo Street, MEB 223, University of Hawaii at Manoa, Honolulu, HI, 96813, USA.
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Teo DCH, Ng PSL, Tan SH, Lim AT, Toh DSL, Chan SY, Cheong HH. Drug-induced liver injury associated with Complementary and Alternative Medicine: a review of adverse event reports in an Asian community from 2009 to 2014. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2016; 16:192. [PMID: 27389194 PMCID: PMC4937524 DOI: 10.1186/s12906-016-1168-z] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Accepted: 06/14/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND The use of Complementary and Alternative Medicine (CAM) has been increasing over the years. A recent review of adverse event reports (AERs) associated with CAM in Singapore found a notable number of AERs submitted. The objectives of this study are to analyse hepatotoxicity cases associated with CAM in Singapore based on spontaneous adverse event reporting to the Health Sciences Authority (HSA), and to highlight safety signals for specific herbal ingredients. METHODS AERs associated with CAM and hepatotoxicity submitted to the Vigilance and Compliance Branch (VCB) of the HSA from 2009 to 2014 were compiled. The following information was extracted and analysed: Demographic information; time to onset; hospitalisation status; outcome; type of hepatotoxicity; ingredients of CAM, and the total daily doses (TDD); concurrent western medicines and health supplements; and reporter details. RESULTS Fifty-seven reports were eligible for analysis. Thirty-five (61.4 %) cases involved Traditional Chinese Medicine (TCM). The Roussel Uclaf Causality Assessment Method was applied in 29 (82.9 %) of these cases, and the median score was 4 (range: 1-8). Chai Hu (Radix bupleuri) was suspected in 11 (31.4 %) cases. TDDs of most ingredients were within recommended doses of the Chinese Pharmacopoeia. CONCLUSIONS Drug-induced liver injury is still poorly understood and more objective assessments are warranted. Reporting of adverse events should be strongly advocated to facilitate future analyses and the understanding of risk-benefit profiles of CAM.
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Affiliation(s)
- Desmond Chun Hwee Teo
- />Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4A Level 3, 18 Science Drive 4, Singapore, S117543 Republic of Singapore
| | - Patricia Suet Leng Ng
- />Vigilance and Compliance Branch, Health Sciences Authority Singapore, 11 Biopolis Way, #11-03, Helios, Singapore, 138667 Singapore
| | - Siew Har Tan
- />Vigilance and Compliance Branch, Health Sciences Authority Singapore, 11 Biopolis Way, #11-03, Helios, Singapore, 138667 Singapore
| | - Adena Theen Lim
- />Vigilance and Compliance Branch, Health Sciences Authority Singapore, 11 Biopolis Way, #11-03, Helios, Singapore, 138667 Singapore
| | - Dorothy Su Lin Toh
- />Vigilance and Compliance Branch, Health Sciences Authority Singapore, 11 Biopolis Way, #11-03, Helios, Singapore, 138667 Singapore
| | - Sui Yung Chan
- />Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4A Level 3, 18 Science Drive 4, Singapore, S117543 Republic of Singapore
| | - Han Hui Cheong
- />Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4A Level 3, 18 Science Drive 4, Singapore, S117543 Republic of Singapore
- />Department of Pharmacy, KK Women’s and Children’s Hospital, 100 Bukit Timah Road, Singapore, 229899 Singapore
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