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Gull N, Arshad F, Naikoo GA, Hassan IU, Pedram MZ, Ahmad A, Aljabali AAA, Mishra V, Satija S, Charbe N, Negi P, Goyal R, Serrano-Aroca Á, Al Zoubi MS, El-Tanani M, Tambuwala MM. Recent Advances in Anticancer Activity of Novel Plant Extracts and Compounds from Curcuma longa in Hepatocellular Carcinoma. J Gastrointest Cancer 2023; 54:368-390. [PMID: 35285010 PMCID: PMC8918363 DOI: 10.1007/s12029-022-00809-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/20/2022] [Indexed: 02/06/2023]
Abstract
PURPOSE Among all forms of cancers, hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. There are several treatment options for HCC ranging from loco-regional therapy to surgical treatment. Yet, there is high morbidity and mortality. Recent research focus has shifted towards more effective and less toxic cancer treatment options. Curcumin, the active ingredient in the Curcuma longa plant, has gained widespread attention in recent years because of its multifunctional properties as an antioxidant, anti-inflammatory, antimicrobial, and anticancer agent. METHODS A systematic search of PubMed, Embase and Google Scholar was performed for studies reporting incidence of HCC, risk factors associated with cirrhosis and experimental use of curcumin as an anti-cancer agent. RESULTS This review exclusively encompasses the anti-cancer properties of curcumin in HCC globally and it's postulated molecular targets of curcumin when used against liver cancers. CONCLUSIONS This review is concluded by presenting the current challenges and future perspectives of novel plant extracts derived from C. longa and the treatment options against cancers.
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Affiliation(s)
- Nighat Gull
- School of Sciences, Maulana Azad National Urdu University, 32, Hyderabad, TS, India
| | - Fareeha Arshad
- Department of Biochemistry, Aligarh Muslim University, U.P., India
| | - Gowhar A Naikoo
- Department of Mathematics and Sciences, College of Arts and Applied Sciences, Dhofar University, Salalah, Sultanate of Oman.
| | - Israr Ul Hassan
- College of Engineering, Dhofar University, Salalah, Sultanate of Oman
| | - Mona Zamani Pedram
- Faculty of Mechanical Engineering-Energy Division, K. N. Toosi University of Technology, P.O. Box: 19395-1999, No. 15-19, Pardis St., Mollasadra Ave., Vanak Sq., Tehran, 1999 143344, Iran
| | - Arif Ahmad
- School of Sciences, Maulana Azad National Urdu University, 32, Hyderabad, TS, India
| | - Alaa A A Aljabali
- Department of Pharmaceutics & Pharmaceutical Technology, Yarmouk University, Irbid, 21163, Jordan
| | - Vijay Mishra
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Saurabh Satija
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Nitin Charbe
- Department of Pharmaceutical Sciences, Rangel College of Pharmacy, Texas A&M University, Kingsville, TX, 78363, USA
| | - Poonam Negi
- School of Pharmaceutical Sciences, Shoolini University of Biotechnology & Management Sciences, Solan, 173229, India
| | - Rohit Goyal
- School of Pharmaceutical Sciences, Shoolini University of Biotechnology & Management Sciences, Solan, 173229, India
| | - Ángel Serrano-Aroca
- Biomaterials & Bioengineering Lab, Centro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia, San Vicente Mártir, 46001, Valencia, Spain
| | - Mazhar S Al Zoubi
- Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan
| | - Mohamed El-Tanani
- Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan
| | - Murtaza M Tambuwala
- School of Pharmacy & Pharmaceutical Sciences, Ulster University, Northern Ireland, Coleraine, BT52 1SA, County Londonderry, UK.
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Antioxidant Activity of Urtica dioica: An Important Property Contributing to Multiple Biological Activities. Antioxidants (Basel) 2022; 11:antiox11122494. [PMID: 36552702 PMCID: PMC9774934 DOI: 10.3390/antiox11122494] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/14/2022] [Accepted: 12/16/2022] [Indexed: 12/23/2022] Open
Abstract
Urtica dioica (UD) is a multi-functional plant known to be used as both food and medicine from ancient times. The plant has the potential to be used as a fertilizer and for biological pest control. It is also used in textile and related industries for its quality fibers. In the recent past, the plant has received great attention for its numerous important biological activities and food applications. The antioxidant activity of UD is the crucial factor supporting its important biological activities, such as anticancer, antidiabetic and anti-inflammatory properties. The antioxidant activity of UD is also found to be protective in different organs, including the brain, liver, lungs, kidney, ovary, and uterus, and may also be protective against diseases associated with these organs. Few clinical studies have endorsed the antioxidant potential of UD in patients. The current work is an attempt to comprehensively compile and discuss the antioxidant activity of UD from in vitro, in vivo and human studies. The insights of the current study would be helpful in getting a panoramic view of the antioxidant potential of UD, and provide direction for optimizing and developing it for therapeutic applications against important diseases and conditions in the near future.
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Govindarasu M, Abirami P, Alharthi SS, Thiruvengadam M, Rajakumar G, Vaiyapuri M. Synthesis, physicochemical characterization, and in vitro evaluation of biodegradable PLGA nanoparticles entrapped to folic acid for targeted delivery of kaempferitrin. Biotechnol Appl Biochem 2022; 69:2387-2398. [PMID: 35020231 DOI: 10.1002/bab.2290] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 11/23/2021] [Indexed: 12/27/2022]
Abstract
Polymeric nanoparticles are widely studied in the treatment of colorectal cancer. Kaempferitrin-loaded nontoxic and biodegradable poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) developed by the solvent emulsion evaporation method by improving its solubility and bioavailability. In order to improve the delivery of kaempferitrin (KM) to cancerous cells, folic acid (FA) combined kaempfertrin PLGA NPs were prepared. The goal of the study was whether PLGA NPs with surface KM and FA could help to prevent colorectal cancer. The synthesis of KM with FA in a nanomedicine could be crucial in the development of colon cancer chemotherapeutics. The physicochemical characteristics of synthesized KM-entrapped PLGA NPs were investigated by XRD, FTIR, zeta potential, and TEM. The KM + FA + PLGA NPs showed particle size with 132.9 ± 1.4 nm, zeta potential -15.0 ± 1.73 mV, encapsulation efficiency 67.92 ± 4.8, and drug-loading capacity 0.463 ± 0.173. In vitro cytotoxicity study on HT-29 cell lines using the MTT assay, the apoptotic study revealed that KM + FA + PLGA NPs have an enhanced cytotoxic effect compared to the KM + PLGA NPs drug solution. These findings suggested that KM + FA + PLGA NPs could be an effective chemotherapeutic drug delivery system in colon adenocarcinoma HT-29 cells.
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Affiliation(s)
- Mydhili Govindarasu
- Molecular Oncology Lab, Department of Biochemistry, Periyar University, Salem, 636011, India
| | - Pari Abirami
- Department of Botany, Seethalakshmi Achi College for Women, Pallathur, Sivagangai, 630107, India
| | - Salman S Alharthi
- Department of Chemistry, College of Science, Taif University, P.O. Box 110999, Taif, 21944, Saudi Arabia
| | - Muthu Thiruvengadam
- Department of Crop Science, College of Sanghuh Life Science, Konkuk University, Seoul, 05029, Republic of Korea
| | - Govindasamy Rajakumar
- Collaborative Innovation Center for Advanced Organic Chemical Materials Co-Constructed by the Province and Ministry, Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules and College of Chemistry and Chemical Engineering, Hubei University, Wuhan, 430062, China
| | - Manju Vaiyapuri
- Molecular Oncology Lab, Department of Biochemistry, Periyar University, Salem, 636011, India
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Akbar Karami A, Sheikhsoleimani M, Reza Memarzadeh M, Haddadi E, Bakhshpour M, Mohammadi N, Mehdi Mirhashemi S. Urtica Dioica Root Extract on Clinical and Biochemical Parameters in Patients with Benign Prostatic Hyperplasia, Randomized Controlled Trial. Pak J Biol Sci 2020; 23:1338-1344. [PMID: 32981268 DOI: 10.3923/pjbs.2020.1338.1344] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND AND OBJECTIVES Benign Prostatic Hyperplasia (BPH) is a common urological disorder as men get older. BPH can cause uncomfortable urinary tract symptoms. Given the high incidence of the disease, further research is an undeniable necessity for its better management. In this research, the efficacy of Urtica Dioica root extract (UDE) on clinical and biochemical parameters were evaluated in this type of patients. MATERIALS AND METHODS Participants were 60 men with BPH that randomly allocated to two equal groups (Intervention = 30 and Comparison = 30). Block balanced Randomization method was performed using a computer by a trained nurse. Intervention and comparison groups received 450 mg day-1 UDE and placebo as tablets for 12 weeks, respectively. The main outcome was changes in International Prostate Symptoms Score (IPSS) from baseline to end of treatment. Data were collected by completing a standard questionnaire and performing relevant tests based on common laboratory methods. RESULTS UDE had an intermediate effect on IPSS, a small effect on serum high-sensitivity C-reactive protein (hs-CRP), intermediate to large effect on malondialdehyde (MDA) levels and intermediate effect on superoxide dismutase (SOD) activity. The magnitude of the effects of UDE on other parameters was overall negligible compared to the comparison and not significant. No side effects were seen in these patients following tablet usage. CONCLUSION UDE consumption for 12 weeks among BPH patients had clinically significant effects on IPSS, serum hs-CRP, MDA and SOD activity.
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Ghasemi S, Moradzadeh M, Hosseini M, Beheshti F, Sadeghnia HR. Beneficial effects of Urtica dioica on scopolamine-induced memory impairment in rats: protection against acetylcholinesterase activity and neuronal oxidative damage. Drug Chem Toxicol 2019; 42:167-175. [PMID: 29745257 DOI: 10.1080/01480545.2018.1463238] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Revised: 04/04/2018] [Accepted: 04/06/2018] [Indexed: 01/03/2023]
Abstract
This study was conducted to investigate protective effects of Urtica dioica extract on acetylcholinesterase (AChE) activity and the oxidative damage of brain tissues in scopolamine-induced memory impairment model. The rats were treated with (1) saline (control), (2) scopolamine, and (3-5) the plant extract (20, 50, or 100 mg/kg) before scopolamine. The traveled distance and the latency to find the platform in Morris water maze (MWM) by scopolamine-treated group were longer while the time spent in target quadrant was shorter than those of the control. Scopolamine decreased the latency to enter the dark in passive avoidance test. Besides, it also increased AChE activity and malondialdehyde (MDA) concentration in the hippocampal and cortical tissues while decreased thiols content and superoxide dismutase (SOD) and catalase (CAT) activities in the brain (p < 0.01-p <0.001). Treatment by the extract reversed all the effects of scopolamine (p < 0.05-p <0.001). According to the results of present study, the beneficial effects of U. dioica on memory can be attributed to its protective effects on oxidative damage of brain tissue and AChE activity.
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Affiliation(s)
- Simagol Ghasemi
- a Division of Neurocognitive Sciences , Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences , Mashhad , Iran
| | - Malihe Moradzadeh
- b Department of New Sciences and Technology, Faculty of Medicine , Mashhad University of Medical Sciences , Mashhad , Iran
- c Golestan Rheumatology Research Center , Golestan University of Medical Sciences , Gorgan , Iran
| | - Mahmoud Hosseini
- a Division of Neurocognitive Sciences , Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences , Mashhad , Iran
| | - Farimah Beheshti
- d Neurogenic Inflammation Research Center , Mashhad University of Medical Sciences , Mashhad , Iran
- e Department of Basic Science and Neuroscience Research Center , Torbat Heydariyeh University of Medical Sciences , Torbat Heydariyeh , Iran
| | - Hamid Reza Sadeghnia
- f Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences , Mashhad , Iran
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Nematgorgani S, Agah S, Shidfar F, Gohari M, Faghihi A. Effects of Urtica dioica leaf extract on inflammation, oxidative stress, ESR, blood cell count and quality of life in patients with inflammatory bowel disease. J Herb Med 2017. [DOI: 10.1016/j.hermed.2017.05.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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The Effects of Silica Nanoparticles on Apoptosis and Autophagy of Glioblastoma Cell Lines. NANOMATERIALS 2017; 7:nano7080230. [PMID: 28825685 PMCID: PMC5575712 DOI: 10.3390/nano7080230] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/15/2017] [Revised: 08/10/2017] [Accepted: 08/11/2017] [Indexed: 12/16/2022]
Abstract
Silica nanoparticles (SiNPs) are one of the most commonly used nanomaterials in various medical applications. However, possible mechanisms of the toxicity caused by SiNPs remain unclear. The study presented here provides novel information on molecular and cellular effects of SiNPs in glioblastoma LBC3 and LN-18 cells. It has been demonstrated that SiNPs of 7 nm, 5–15 nm and 10–20 nm induce time- and dose-dependent cytotoxicity in LBC3 and LN-18 cell lines. In contrast to glioblastoma cells, we observed only weak reduction in viability of normal skin fibroblasts treated with SiNPs. Furthermore, in LBC3 cells treated with 5–15 nm SiNPs we noticed induction of apoptosis and necrosis, while in LN-18 cells only necrosis. The 5–15 nm SiNPs were also found to cause oxidative stress, a loss in mitochondrial membrane potential, and changes in the ultrastructure of the mitochondria in LBC3 cells. Quantitative real-time PCR results showed that in LBC3 cells the mRNA levels of pro-apoptotic genes Bim, Bax, Puma, and Noxa were significantly upregulated. An increase in activity of caspase-9 in these cells was also observed. Moreover, the activation of SiNP-induced autophagy was demonstrated in LBC3 cells as shown by an increase in LC3-II/LC3-I ratio, the upregulation of Atg5 gene and an increase in AVOs-positive cells. In conclusion, this research provides novel information concerning molecular mechanisms of apoptosis and autophagy in LBC3 cells.
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Kilic O, Akand M, Karabagli P, Piskin MM. Hemostatic Efficacy and Histopathological Effects of Ankaferd Blood Stopper in an Experimental Rat Model of Cyclophosphamide-induced Hemorrhagic Cystitis. Urology 2016; 94:313.e7-313.e13. [PMID: 27215482 DOI: 10.1016/j.urology.2016.05.029] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Revised: 04/14/2016] [Accepted: 05/14/2016] [Indexed: 10/21/2022]
Abstract
OBJECTIVE To evaluate the hemostatic efficacy and histopathological effects of Ankaferd Blood Stopper (ABS) in an experimental rat model of cyclophosphamide-induced (CYP) hemorrhagic cystitis (HC). MATERIALS AND METHODS Forty male Sprague-Dawley rats were included in the study. Firstly, 10 rats were divided equally into 2 groups where the first group was administered only an intraperitoneal (i.p.) injection of normal saline to constitute the negative control group (CON). The remaining 5 rats were administered only a single i.p. injection of CYP (without any further treatment) for induction of HC to constitute the positive control group (HC). Subsequently, the remaining 30 rats, which also received i.p. CYP for induction of HC, were divided into 3 groups to which intravesical saline (SAL group), epinephrine (EPN group), and ABS (ANK group) were administered for 3 consecutive days. Ten days after the third instillation, cystectomy was performed for histopathological examination. Specimens were evaluated for presence of congestion, edema, necrosis, ulceration, and regenerated epithelium, and scores were given for each parameter according to the severity. RESULTS No statistically significant difference was observed for congestion, edema, necrosis, and ulceration between HC-SAL, and also between CON-ANK groups (all P values >.05). There was a significant difference for total scores between EPN and ANK groups (P = .009). There was statistically significant difference for regenerating epithelium between CON-EPN, CON-ANK, HC-ANK, and SAL-ANK groups. CONCLUSION Intravesical administration of ABS is at least as efficacious as EPN in terms of congestion, edema, necrosis, and ulceration. Moreover, ABS can be considered as a better option in inducing regenerating epithelium than EPN.
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Affiliation(s)
- Ozcan Kilic
- Department of Urology, School of Medicine, Selcuk University, Konya, Turkey
| | - Murat Akand
- Department of Urology, School of Medicine, Selcuk University, Konya, Turkey.
| | - Pinar Karabagli
- Department of Pathology, School of Medicine, Selcuk University, Konya, Turkey
| | - Mehmet Mesut Piskin
- Department of Urology, Meram Medical School, Necmettin Erbakan University, Konya, Turkey
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Yu W, Zhang X, Liu J, Wang X, Li S, Liu R, Liao N, Zhang T, Hai C. Cyclosporine A Suppressed Glucose Oxidase Induced P53 Mitochondrial Translocation and Hepatic Cell Apoptosis through Blocking Mitochondrial Permeability Transition. Int J Biol Sci 2016; 12:198-209. [PMID: 26884717 PMCID: PMC4737676 DOI: 10.7150/ijbs.13716] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Accepted: 11/09/2015] [Indexed: 12/19/2022] Open
Abstract
P53 is known as a transcription factor to control apoptotic cell death through regulating a series of target genes in nucleus. There is accumulating evidences show that p53 can directly induce cell apoptosis through transcription independent way at mitochondria. However, the mechanism by which p53 translocation into mitochondria in response to oxidative stress remains unclear. Here, glucose oxidase (GOX) was used to induce ROS generation in HepG2 cells and liver tissues of mice. The results showed that p53 was stabilized and translocated to mitochondria in a time and dose dependent manner after GOX exposure. Interestingly, as an inhibitor of mitochondrial permeability transition, cyclosporine A (CsA) was able to effectively reduce GOX mediated mitochondrial p53 distribution without influencing on the expression of p53 target genes including Bcl-2 and Bax. These indicated that CsA could just block p53 entering into mitochondria, but not affect p53-dependent transcription. Meanwhile, CsA failed to inhibit the ROS generation induced by GOX, which indicated that CsA had no antioxidant function. Moreover, GOX induced typical apoptosis characteristics including, mitochondrial dysfunction, accumulation of Bax and release of cytochrome C in mitochondria, accompanied with activation of caspase-9 and caspase-3. These processions were suppressed after pretreatment with CsA and pifithrin-μ (PFT-μ, a specific inhibitor of p53 mitochondrial translocation). In vivo, CsA was able to attenuate p53 mitochondrial distribution and protect mice liver against from GOX mediated apoptotic cell death. Taken together, these suggested that CsA could suppress ROS-mediated p53 mitochondrial distribution and cell apoptosis depended on its inhibition effect to mitochondrial permeability transition. It might be used to rescue the hepatic cell apoptosis in the patients with acute liver injury.
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Affiliation(s)
- Weihua Yu
- 1. Department of Toxicology, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Lab of Free radical biology and medicine, School of Public Health, The Fourth Military Medical University, Xi'an, 710032, P. R. China
| | - Xiaodi Zhang
- 1. Department of Toxicology, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Lab of Free radical biology and medicine, School of Public Health, The Fourth Military Medical University, Xi'an, 710032, P. R. China
| | - Jiangzheng Liu
- 1. Department of Toxicology, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Lab of Free radical biology and medicine, School of Public Health, The Fourth Military Medical University, Xi'an, 710032, P. R. China
| | - Xin Wang
- 1. Department of Toxicology, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Lab of Free radical biology and medicine, School of Public Health, The Fourth Military Medical University, Xi'an, 710032, P. R. China
| | - Shuang Li
- 2. Department of Cardiology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, 710032, China
| | - Rui Liu
- 1. Department of Toxicology, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Lab of Free radical biology and medicine, School of Public Health, The Fourth Military Medical University, Xi'an, 710032, P. R. China
| | - Nai Liao
- 1. Department of Toxicology, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Lab of Free radical biology and medicine, School of Public Health, The Fourth Military Medical University, Xi'an, 710032, P. R. China
| | - Tao Zhang
- 1. Department of Toxicology, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Lab of Free radical biology and medicine, School of Public Health, The Fourth Military Medical University, Xi'an, 710032, P. R. China
| | - Chunxu Hai
- 1. Department of Toxicology, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Lab of Free radical biology and medicine, School of Public Health, The Fourth Military Medical University, Xi'an, 710032, P. R. China
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Lactulose accelerates liver regeneration in rats by inducing hydrogen. J Surg Res 2015; 195:128-35. [PMID: 25700936 DOI: 10.1016/j.jss.2015.01.034] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2014] [Revised: 01/04/2015] [Accepted: 01/21/2015] [Indexed: 11/23/2022]
Abstract
BACKGROUND Oxidative stress and inflammation are implicated in the process of liver regeneration. Lactulose orally administered can be bacterially fermented and induces dramatic amounts of endogenous hydrogen. Hydrogen has been confirmed to have antioxidant and anti-inflammatory properties. This study investigated the potential influence of lactulose administration on liver regeneration. MATERIALS AND METHODS Antibiotics were used to suppress bacterial fermentation of lactulose, and hydrogen-rich saline was used as a supplementary measure of exogenous hydrogen. The liver regeneration model was produced in Sprague-Dawley rats through 70% partial hepatectomy. RESULTS Compared with non-lactulose-treated group, lactulose administration remarkably increased the weights of remnant liver and inhibited increases in serum levels of transaminases more notably. In the lactulose-treated group, increases of markers for regeneration, such as proliferating cell nuclear antigen and cyclin D1, were highly elevated. Biochemically, lactulose administration increased liver superoxide dismutase activity and decreased malondialdehyde content. In the lactulose-treated group, excessive increases in inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-α, were inhibited significantly. Increased heme oxygenase-1 and superoxide dismutase 2 expression were also observed after lactulose treatment. The antibiotics suppressed the regeneration-promoting effect of lactulose by reducing hydrogen production, whereas supplementing hydrogen by hydrogen-rich saline would get a similar regeneration-promoting effect as lactulose administration. CONCLUSIONS Lactulose administration accelerates posthepatectomized liver regeneration in rats by inducing hydrogen, which may result from attenuation of the oxidative stress response and excessive inflammatory response.
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