|
1
|
Naidoo K, Khathi A. Investigating the Effects of Gossypetin on Liver Health in Diet-Induced Pre-Diabetic Male Sprague Dawley Rats. Molecules 2025; 30:1834. [PMID: 40333901 PMCID: PMC12029341 DOI: 10.3390/molecules30081834] [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: 02/13/2025] [Revised: 03/25/2025] [Accepted: 04/17/2025] [Indexed: 05/09/2025] Open
Abstract
The rising prevalence of non-alcoholic fatty liver disease among patients with type 2 diabetes mellitus has emerged as a global health challenge. Gossypetin (GTIN) is a natural flavonoid which has recently demonstrated antihyperglycaemic, antioxidant, and anti-inflammatory effects. Despite these findings, no studies have investigated its effects on liver health in the pre-diabetic state. Hence, this study aimed to investigate the effects of GTIN on liver health in diet-induced pre-diabetic male rats in the presence and absence of dietary intervention and to compare these effects with those of metformin (MET). Following 20 weeks of pre-diabetes induction, the animals were divided into six groups (n = 6) as follows: non-pre-diabetic (NPD) control, pre-diabetic (PD) control, and PD groups treated with GTIN (15 mg/kg body weight (bw)) or metformin (500 mg/kg bw) on either a normal diet or a high-fat, high-carbohydrate diet for 12 weeks. The results showed that the PD group had significantly higher liver triglycerides (TAG), liver weights, sterol regulatory binding element regulatory protein-1c (SREBP-1c), malondialdehyde (MDA) levels, and liver injury enzyme levels, along with decreased liver superoxide dismutase (SOD) activity, glutathione peroxidase (GPx) activity, and plasma bilirubin levels in comparison to NPD. Histologically, there was an increased lipid droplet accumulation and structural disarray in the PD group. GTIN treatment significantly reduced liver TAGs, liver weights, and plasma SREBP-1c levels, as well as improved liver SOD and GPx activity while decreasing liver MDA levels and liver injury enzymes in comparison to the PD control. Notably, GTIN treatment increased plasma bilirubin levels. Liver histology in the GTIN-treated groups revealed decreased lipid droplet accumulation and improved tissue integrity. Similar results were observed for the liver parameters in the MET-treated groups. The findings of this study may suggest that GTIN and MET exhibit therapeutic effects on liver health in diet-induced pre-diabetes in both the presence and absence of diet intervention. Dietary intervention may confer beneficial effects on liver health, with the most favorable therapeutic outcomes observed through a combination of treatment with dietary intervention. Additionally, GTIN may exhibit greater hepatoprotective effects than MET in rats without dietary intervention.
Collapse
Affiliation(s)
- Karishma Naidoo
- Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa;
| | | |
Collapse
|
|
2
|
Anwar MJ, Hameed A, Khan MU, Mazhar A, Manzoor HMI. Development and exploration of casein-based nano-encapsulation of mangiferin for cow milk allergy management and immunomodulation. FOOD BIOSCI 2025; 66:106278. [DOI: https:/doi.org/10.1016/j.fbio.2025.106278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/13/2025]
|
|
3
|
Anwar MJ, Hameed A, Khan MU, Mazhar A, Manzoor HMI. Development and exploration of casein-based nano-encapsulation of mangiferin for cow milk allergy management and immunomodulation. FOOD BIOSCI 2025; 66:106278. [DOI: 10.1016/j.fbio.2025.106278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/04/2025]
|
|
4
|
Zhu R, Xu C, Jiang S, Xia J, Wu B, Zhang S, Zhou J, Liu H, Li H, Lou J. Risk factor analysis and predictive model construction of lean MAFLD: a cross-sectional study of a health check-up population in China. Eur J Med Res 2025; 30:137. [PMID: 40001266 PMCID: PMC11863909 DOI: 10.1186/s40001-025-02373-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 02/10/2025] [Indexed: 02/27/2025] Open
Abstract
AIM Cardiovascular disease morbidity and mortality rates are high in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). The objective of this study was to analyze the risk factors and differences between lean MAFLD and overweight MAFLD, and establish and validate a nomogram model for predicting lean MAFLD. METHODS This retrospective cross-sectional study included 4363 participants who underwent annual health checkup at Yuyao from 2019 to 2022. The study population was stratified into three groups: non-MAFLD, lean MAFLD (defined as the presence of fatty liver changes as determined by ultrasound in individuals with a BMI < 25 kg/m2), and overweight MAFLD (BMI ≥ 25.0 kg/m2). Subsequent modeling analysis was conducted in a population that included healthy subjects with < 25 kg/m2 (n = 2104) and subjects with lean MAFLD (n = 849). The study population was randomly split (7:3 ratio) to a training vs. a validation cohort. Risk factors for lean MAFLD was identify by multivariate regression of the training cohort, and used to construct a nomogram to estimate the probability of lean MAFLD. Model performance was examined using the receiver operating characteristic (ROC) curve analysis and k-fold cross-validation (k = 5). Decision curve analysis (DCA) was applied to evaluate the clinical usefulness of the prediction model. RESULTS The multivariate regression analysis indicated that the triglycerides and glucose index (TyG) was the most significant risk factor for lean MAFLD (OR: 4.03, 95% CI 2.806-5.786). The restricted cubic spline curves (RCS) regression model demonstrated that the relationships between systolic pressure (SBP), alanine aminotransferase (ALT), serum urate (UA), total cholesterol (TCHO), triglyceride (TG), triglyceride glucose (TyG) index, high density lipoprotein cholesterol (HDLC), and MAFLD were nonlinear and the cutoff values for lean MAFLD and overweight MAFLD were different. The nomogram was constructed based on seven predictors: glycosylated hemoglobin A1c (HbA1c), serum ferritin (SF), ALT, UA, BMI, TyG index, and age. In the validation cohort, the area under the ROC curve was 0.866 (95% CI 0.842-0.891), with 83.8% sensitivity and 76.6% specificity at the optimal cutoff. The PPV and NPV was 63.3% and 90.8%, respectively. Furthermore, we used fivefold cross-validation and the average area under the ROC curve was 0.866 (Figure S3). The calibration curves for the model's predictions and the actual outcomes were in good agreement. The DCA findings demonstrated that the nomogram model was clinically useful throughout a broad threshold probability range. CONCLUSIONS Lean and overweight MAFLD exhibit distinct metabolic profiles. The nomogram model developed in this study is designed to assist clinicians in the early identification of high-risk individuals with lean MAFLD, including those with a normal BMI but at metabolic risk, as well as those with abnormal blood lipid, glucose, uric acid or transaminase levels. In addition, this model enhances screening efforts in communities and medical screening centers, ultimately ensuring more timely and effective medical services for patients.
Collapse
Affiliation(s)
- Ruya Zhu
- Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, 315010, Zhejiang, China
| | - Caicai Xu
- Chronic Liver Disease Center, The Affiliated Yangming Hospital of Ningbo University, Zhejiang, 315400, China
| | - Suwen Jiang
- Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, 315010, Zhejiang, China
| | - Jianping Xia
- Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, 315010, Zhejiang, China
| | - Boming Wu
- Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, 315010, Zhejiang, China
| | - Sijia Zhang
- Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, 315010, Zhejiang, China
| | - Jing Zhou
- Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, 315010, Zhejiang, China
| | - Hongliang Liu
- Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, 315010, Zhejiang, China
| | - Hongshan Li
- Liver Disease Department of Integrative Medicine, Ningbo No. 2 Hospital, Ningbo, 315010, Zhejiang, China.
| | - Jianjun Lou
- Chronic Liver Disease Center, The Affiliated Yangming Hospital of Ningbo University, Zhejiang, 315400, China.
| |
Collapse
|
|
5
|
Pajuelo-Vasquez R, Benites-Meza JK, Durango-Chavez HV, Salinas-Sedo G, Toro-Huamanchumo CJ. Diagnostic performance of the GGT/HDL-C ratio for NAFLD in adults with obesity undergoing bariatric surgery. Diabetes Res Clin Pract 2024; 211:111649. [PMID: 38574896 DOI: 10.1016/j.diabres.2024.111649] [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] [Received: 07/28/2023] [Accepted: 04/01/2024] [Indexed: 04/06/2024]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has become the most frequent liver disease, closely related with metabolic risk factors such as obesity, insulin resistance, dyslipidemia, diabetes mellitus, and metabolic syndrome. In this context, γ-Glutamyl transpeptidase (GGT) and high-density lipoprotein cholesterol (HDL-C) have shown correlations with steatosis severity and metabolic syndrome, respectively. This positions the GGT/HDL-C ratio as a potential diagnostic indicator for NAFLD. OBJECTIVE To assess the diagnostic performance of the GGT/HDL-C ratio for NAFLD in adults with obesity undergoing bariatric surgery. METHODS We conducted an analytical cross-sectional study, designed as a diagnostic test evaluation. A secondary database of 249 adults with obesity was analyzed. The optimal cut-off point was ascertained using three methodologies, and five adjustment models were constructed for the total population, further stratified by sex. RESULTS The optimal cut-off point was 20.5 U/mmol and the AUC of the ratio was 0.81 (95% CI: 0.64-0.98), with sensitivity and specificity being 82.5% and 77.8%, respectively. In the overall group with an elevated GGT/HDL-C ratio, the prevalence of NAFLD increased by 14% (PR: 1.14; 95% CI: 1.04-1.33). Specifically, women displaying this altered ratio showed a 19% increased prevalence (PR: 1.19; 95% CI: 1.07-1.42) compared to those with normal values. CONCLUSIONS The GGT/HDL-C ratio is a promising biomarker for the diagnosis of NAFLD in an adult population living with obesity.
Collapse
Affiliation(s)
- Renzo Pajuelo-Vasquez
- CHANGE Research Working Group, Facultad de Ciencias de la Salud, Carrera de Medicina Humana, Universidad Científica del Sur, Lima, Peru
| | - Jerry K Benites-Meza
- Sociedad Científica de Estudiantes de Medicina de la Universidad Nacional de Trujillo, Trujillo, Peru; Grupo Peruano de Investigación Epidemiológica, Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud, Universidad San Ignacio de Loyola, Lima, Peru
| | | | | | - Carlos J Toro-Huamanchumo
- OBEMET Center for Obesity and Metabolic Health, Lima, Peru; Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud, Universidad San Ignacio de Loyola, Lima, Peru; Nutrition and Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
| |
Collapse
|
|
6
|
Li S, Duan F, Li S, Lu B. Administration of silymarin in NAFLD/NASH: A systematic review and meta-analysis. Ann Hepatol 2024; 29:101174. [PMID: 38579127 DOI: 10.1016/j.aohep.2023.101174] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 10/07/2023] [Accepted: 10/16/2023] [Indexed: 04/07/2024]
Abstract
INTRODUCTION AND OBJECTIVES Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with a high prevalence worldwide and poses serious harm to human health. There is growing evidence suggesting that the administration of specific supplements or nutrients may slow NAFLD progression. Silymarin is a hepatoprotective extract of milk thistle, but its efficacy in NAFLD remains unclear. MATERIALS AND METHODS Relevant studies were searched in PubMed, Embase, the Cochrane Library, Web of Science, clinicaltrails.gov, and China National Knowledge Infrastructure and were screened according to the eligibility criteria. Data were analyzed using Revman 5.3. Continuous values and dichotomous values were pooled using the standard mean difference (SMD) and odds ratio (OR). Heterogeneity was evaluated using the Cochran's Q test (I2 statistic). A P<0.05 was considered statistically significant. RESULTS A total of 26 randomized controlled trials involving 2,375 patients were included in this study. Administration of silymarin significantly reduced the levels of TC (SMD[95%CI]=-0.85[-1.23, -0.47]), TG (SMD[95%CI]=-0.62[-1.14, -0.10]), LDL-C (SMD[95%CI]=-0.81[-1.31, -0.31]), FI (SMD[95%CI]=-0.59[-0.91, -0.28]) and HOMA-IR (SMD[95%CI]=-0.37[-0.77, 0.04]), and increased the level of HDL-C (SMD[95%CI]=0.46[0.03, 0.89]). In addition, silymarin attenuated liver injury as indicated by the decreased levels of ALT (SMD[95%CI]=-12.39[-19.69, -5.08]) and AST (SMD[95% CI]=-10.97[-15.51, -6.43]). The levels of fatty liver index (SMD[95%CI]=-6.64[-10.59, -2.69]) and fatty liver score (SMD[95%CI]=-0.51[-0.69, -0.33]) were also decreased. Liver histology of the intervention group revealed significantly improved hepatic steatosis (OR[95%CI]=3.25[1.80, 5.87]). CONCLUSIONS Silymarin can regulate energy metabolism, attenuate liver damage, and improve liver histology in NAFLD patients. However, the effects of silymarin will need to be confirmed by further research.
Collapse
Affiliation(s)
- Shudi Li
- The Second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou 450000, China
| | - Fei Duan
- The First Affiliated Hospital of Henan University of TCM Zhengzhou 450000, China
| | - Suling Li
- The First Affiliated Hospital of Henan University of TCM Zhengzhou 450000, China
| | - Baoping Lu
- Henan University of Chinese Medicine, Zhengzhou 450046, China.
| |
Collapse
|
|
7
|
Raya-Cano E, Molina-Luque R, Vaquero-Abellán M, Molina-Recio G, Jiménez-Mérida R, Romero-Saldaña M. Metabolic syndrome and transaminases: systematic review and meta-analysis. Diabetol Metab Syndr 2023; 15:220. [PMID: 37899468 PMCID: PMC10614379 DOI: 10.1186/s13098-023-01200-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 10/24/2023] [Indexed: 10/31/2023] Open
Abstract
BACKGROUND Metabolic syndrome (MetS) is a group of metabolic abnormalities characterised by hypertension, central obesity, dyslipidaemia and dysregulation of blood glucose, associated with the risk of diabetes, cardiovascular disease and overall mortality. The presence of elevated liver enzymes may precede the development of MetS, with alterations of the liver being observed that are directly related to metabolic problems. The study aims to provide the best evidence on the association between liver enzymes (ALT, AST, GGT) and MetS by determining the effect size of these biomarkers. METHODS A systematic review and meta-analysis of studies indexed in PubMed and Scopus databases were performed. Study quality was assessed using the STROBE tool. The Grade Pro tool was used to evaluate the evidence, and the quantitative synthesis was performed using RevMan (Cochrane Collaboration). RESULTS Seventeen articles comparing liver enzyme concentrations between 76,686 with MetS (MetS+) and 201,855 without MetS (MetS-) subjects were included. The concentration of ALT, AST and GGT in the MetS + subjects was significantly higher than in the control group 7.13 IU/L (CI95% 5.73-8.54; p < 0.00001; I2 = 96%), 2.68 IU/L (CI95% 1.82-3.54; p < 0.00001; I2 = 96%) and 11.20 IU/L (CI95% 7.11-15.29; p < 0.00001; I2 = 96%), respectively. CONCLUSIONS The evaluation of the relationship of liver enzymes in the pathophysiological process of MetS could lead to new insights into early diagnosis.
Collapse
Affiliation(s)
- Elena Raya-Cano
- Faculty of Medicine and Nursing, University of Córdoba, Avd. Menéndez Pidal N/N, Córdoba, 14004, Spain
| | - Rafael Molina-Luque
- Faculty of Medicine and Nursing, University of Córdoba, Avd. Menéndez Pidal N/N, Córdoba, 14004, Spain.
- Lifestyles, Innovation and Health (GA-16), Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain.
| | - Manuel Vaquero-Abellán
- Faculty of Medicine and Nursing, University of Córdoba, Avd. Menéndez Pidal N/N, Córdoba, 14004, Spain
| | - Guillermo Molina-Recio
- Faculty of Medicine and Nursing, University of Córdoba, Avd. Menéndez Pidal N/N, Córdoba, 14004, Spain
- Lifestyles, Innovation and Health (GA-16), Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain
| | - Rocío Jiménez-Mérida
- Faculty of Medicine and Nursing, University of Córdoba, Avd. Menéndez Pidal N/N, Córdoba, 14004, Spain
| | - Manuel Romero-Saldaña
- Faculty of Medicine and Nursing, University of Córdoba, Avd. Menéndez Pidal N/N, Córdoba, 14004, Spain
- Lifestyles, Innovation and Health (GA-16), Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain
| |
Collapse
|
|
8
|
Korobeinikova AV, Zlobovskaya OA, Sheptulina AF, Ashniev GA, Bobrova MM, Yafarova AA, Akasheva DU, Kabieva SS, Bakoev SY, Zagaynova AV, Lukashina MV, Abramov IA, Pokrovskaya MS, Doludin YV, Tolkacheva LR, Kurnosov AS, Zyatenkova EV, Lavrenova EA, Efimova IA, Glazunova EV, Kiselev AR, Shipulin GA, Kontsevaya AV, Keskinov AA, Yudin VS, Makarov VV, Drapkina OM, Yudin SM. Gut Microbiota Patterns in Patients with Non-Alcoholic Fatty Liver Disease: A Comprehensive Assessment Using Three Analysis Methods. Int J Mol Sci 2023; 24:15272. [PMID: 37894951 PMCID: PMC10607775 DOI: 10.3390/ijms242015272] [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: 08/17/2023] [Revised: 09/01/2023] [Accepted: 09/05/2023] [Indexed: 10/29/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease worldwide, affecting nearly 25% of the global adult population. Increasing evidence suggests that functional and compositional changes in the gut microbiota may contribute to the development and promote the progression of NAFLD. 16S rRNA gene next-generation sequencing is widely used to determine specific features of the NAFLD microbiome, but a complex system such as the gut microbiota requires a comprehensive approach. We used three different approaches: MALDI-TOF-MS of bacterial cultures, qPCR, and 16S NGS sequencing, as well as a wide variety of statistical methods to assess the differences in gut microbiota composition between NAFLD patients without significant fibrosis and the control group. The listed methods showed enrichment in Collinsella sp. and Oscillospiraceae for the control samples and enrichment in Lachnospiraceae (and in particular Dorea sp.) and Veillonellaceae in NAFLD. The families, Bifidobacteriaceae, Lactobacillaceae, and Enterococcaceae (particularly Enterococcus faecium and Enterococcus faecalis), were also found to be important taxa for NAFLD microbiome evaluation. Considering individual method observations, an increase in Candida krusei and a decrease in Bacteroides uniformis for NAFLD patients were detected using MALDI-TOF-MS. An increase in Gracilibacteraceae, Chitinophagaceae, Pirellulaceae, Erysipelatoclostridiaceae, Muribaculaceae, and Comamonadaceae, and a decrease in Acidaminococcaceae in NAFLD were observed with 16S NGS, and enrichment in Fusobacterium nucleatum was shown using qPCR analysis. These findings confirm that NAFLD is associated with changes in gut microbiota composition. Further investigations are required to determine the cause-and-effect relationships and the impact of microbiota-derived compounds on the development and progression of NAFLD.
Collapse
Affiliation(s)
- Anna V. Korobeinikova
- Centre for Strategic Planning and Management of Biomedical Health Risks of Federal Medical Biological Agency, Pogodinskaya Str., 10/1, 119121 Moscow, Russia; (A.V.K.); (S.S.K.); (S.Y.B.); (M.V.L.); (A.S.K.)
| | - Olga A. Zlobovskaya
- Centre for Strategic Planning and Management of Biomedical Health Risks of Federal Medical Biological Agency, Pogodinskaya Str., 10/1, 119121 Moscow, Russia; (A.V.K.); (S.S.K.); (S.Y.B.); (M.V.L.); (A.S.K.)
| | - Anna F. Sheptulina
- National Medical Research Center for Therapy and Preventive Medicine, Petroverigskyj Lane 10, bld.3, 101990 Moscow, Russia; (A.F.S.); (A.A.Y.); (D.U.A.)
| | - German A. Ashniev
- Centre for Strategic Planning and Management of Biomedical Health Risks of Federal Medical Biological Agency, Pogodinskaya Str., 10/1, 119121 Moscow, Russia; (A.V.K.); (S.S.K.); (S.Y.B.); (M.V.L.); (A.S.K.)
| | - Maria M. Bobrova
- Centre for Strategic Planning and Management of Biomedical Health Risks of Federal Medical Biological Agency, Pogodinskaya Str., 10/1, 119121 Moscow, Russia; (A.V.K.); (S.S.K.); (S.Y.B.); (M.V.L.); (A.S.K.)
| | - Adel A. Yafarova
- National Medical Research Center for Therapy and Preventive Medicine, Petroverigskyj Lane 10, bld.3, 101990 Moscow, Russia; (A.F.S.); (A.A.Y.); (D.U.A.)
| | - Dariga U. Akasheva
- National Medical Research Center for Therapy and Preventive Medicine, Petroverigskyj Lane 10, bld.3, 101990 Moscow, Russia; (A.F.S.); (A.A.Y.); (D.U.A.)
| | - Shuanat Sh. Kabieva
- Centre for Strategic Planning and Management of Biomedical Health Risks of Federal Medical Biological Agency, Pogodinskaya Str., 10/1, 119121 Moscow, Russia; (A.V.K.); (S.S.K.); (S.Y.B.); (M.V.L.); (A.S.K.)
| | - Siroj Yu. Bakoev
- Centre for Strategic Planning and Management of Biomedical Health Risks of Federal Medical Biological Agency, Pogodinskaya Str., 10/1, 119121 Moscow, Russia; (A.V.K.); (S.S.K.); (S.Y.B.); (M.V.L.); (A.S.K.)
| | - Anjelica V. Zagaynova
- Centre for Strategic Planning and Management of Biomedical Health Risks of Federal Medical Biological Agency, Pogodinskaya Str., 10/1, 119121 Moscow, Russia; (A.V.K.); (S.S.K.); (S.Y.B.); (M.V.L.); (A.S.K.)
| | - Maria V. Lukashina
- Centre for Strategic Planning and Management of Biomedical Health Risks of Federal Medical Biological Agency, Pogodinskaya Str., 10/1, 119121 Moscow, Russia; (A.V.K.); (S.S.K.); (S.Y.B.); (M.V.L.); (A.S.K.)
| | - Ivan A. Abramov
- Centre for Strategic Planning and Management of Biomedical Health Risks of Federal Medical Biological Agency, Pogodinskaya Str., 10/1, 119121 Moscow, Russia; (A.V.K.); (S.S.K.); (S.Y.B.); (M.V.L.); (A.S.K.)
| | - Mariya S. Pokrovskaya
- National Medical Research Center for Therapy and Preventive Medicine, Petroverigskyj Lane 10, bld.3, 101990 Moscow, Russia; (A.F.S.); (A.A.Y.); (D.U.A.)
| | - Yurii V. Doludin
- National Medical Research Center for Therapy and Preventive Medicine, Petroverigskyj Lane 10, bld.3, 101990 Moscow, Russia; (A.F.S.); (A.A.Y.); (D.U.A.)
| | - Larisa R. Tolkacheva
- Centre for Strategic Planning and Management of Biomedical Health Risks of Federal Medical Biological Agency, Pogodinskaya Str., 10/1, 119121 Moscow, Russia; (A.V.K.); (S.S.K.); (S.Y.B.); (M.V.L.); (A.S.K.)
| | - Alexander S. Kurnosov
- Centre for Strategic Planning and Management of Biomedical Health Risks of Federal Medical Biological Agency, Pogodinskaya Str., 10/1, 119121 Moscow, Russia; (A.V.K.); (S.S.K.); (S.Y.B.); (M.V.L.); (A.S.K.)
| | - Elena V. Zyatenkova
- National Medical Research Center for Therapy and Preventive Medicine, Petroverigskyj Lane 10, bld.3, 101990 Moscow, Russia; (A.F.S.); (A.A.Y.); (D.U.A.)
| | - Evgeniya A. Lavrenova
- National Medical Research Center for Therapy and Preventive Medicine, Petroverigskyj Lane 10, bld.3, 101990 Moscow, Russia; (A.F.S.); (A.A.Y.); (D.U.A.)
| | - Irina A. Efimova
- National Medical Research Center for Therapy and Preventive Medicine, Petroverigskyj Lane 10, bld.3, 101990 Moscow, Russia; (A.F.S.); (A.A.Y.); (D.U.A.)
| | - Evgeniya V. Glazunova
- Centre for Strategic Planning and Management of Biomedical Health Risks of Federal Medical Biological Agency, Pogodinskaya Str., 10/1, 119121 Moscow, Russia; (A.V.K.); (S.S.K.); (S.Y.B.); (M.V.L.); (A.S.K.)
| | - Anton R. Kiselev
- National Medical Research Center for Therapy and Preventive Medicine, Petroverigskyj Lane 10, bld.3, 101990 Moscow, Russia; (A.F.S.); (A.A.Y.); (D.U.A.)
| | - German A. Shipulin
- Centre for Strategic Planning and Management of Biomedical Health Risks of Federal Medical Biological Agency, Pogodinskaya Str., 10/1, 119121 Moscow, Russia; (A.V.K.); (S.S.K.); (S.Y.B.); (M.V.L.); (A.S.K.)
| | - Anna V. Kontsevaya
- National Medical Research Center for Therapy and Preventive Medicine, Petroverigskyj Lane 10, bld.3, 101990 Moscow, Russia; (A.F.S.); (A.A.Y.); (D.U.A.)
| | - Anton A. Keskinov
- Centre for Strategic Planning and Management of Biomedical Health Risks of Federal Medical Biological Agency, Pogodinskaya Str., 10/1, 119121 Moscow, Russia; (A.V.K.); (S.S.K.); (S.Y.B.); (M.V.L.); (A.S.K.)
| | - Vladimir S. Yudin
- Centre for Strategic Planning and Management of Biomedical Health Risks of Federal Medical Biological Agency, Pogodinskaya Str., 10/1, 119121 Moscow, Russia; (A.V.K.); (S.S.K.); (S.Y.B.); (M.V.L.); (A.S.K.)
| | - Valentin V. Makarov
- Centre for Strategic Planning and Management of Biomedical Health Risks of Federal Medical Biological Agency, Pogodinskaya Str., 10/1, 119121 Moscow, Russia; (A.V.K.); (S.S.K.); (S.Y.B.); (M.V.L.); (A.S.K.)
| | - Oxana M. Drapkina
- National Medical Research Center for Therapy and Preventive Medicine, Petroverigskyj Lane 10, bld.3, 101990 Moscow, Russia; (A.F.S.); (A.A.Y.); (D.U.A.)
| | - Sergey M. Yudin
- Centre for Strategic Planning and Management of Biomedical Health Risks of Federal Medical Biological Agency, Pogodinskaya Str., 10/1, 119121 Moscow, Russia; (A.V.K.); (S.S.K.); (S.Y.B.); (M.V.L.); (A.S.K.)
| |
Collapse
|
|
9
|
Yao M, Zhou P, Qin YY, Wang L, Yao DF. Mitochondrial carnitine palmitoyltransferase-II dysfunction: A possible novel mechanism for nonalcoholic fatty liver disease in hepatocarcinogenesis. World J Gastroenterol 2023; 29:1765-1778. [PMID: 37032731 PMCID: PMC10080702 DOI: 10.3748/wjg.v29.i12.1765] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 08/04/2022] [Accepted: 03/09/2023] [Indexed: 03/28/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) or metabolic-associated fatty liver disease has been characterized by the lipid accumulation with injury of hepatocytes and has become one of the most common chronic liver diseases in the world. The complex mechanisms of NAFLD formation are still under identification. Carnitine palmitoyltransferase-II (CPT-II) on inner mitochondrial membrane (IMM) regulates long chain fatty acid β-oxidation, and its abnormality has had more and more attention paid to it by basic and clinical research in NAFLD. The sequences of its peptide chain and DNA nucleotides have been identified, and the catalytic activity of CPT-II is affected on its gene mutations, deficiency, enzymatic thermal instability, circulating carnitine level and so on. Recently, the CPT-II dysfunction has been discovered in models of liver lipid accumulation. Meanwhile, the malignant transformation of hepatocyte-related CD44+ stem T cell activation, high levels of tumor-related biomarkers (AFP, GPC3) and abnormal activation of Wnt3a expression as a key signal molecule of the Wnt/β-catenin pathway run parallel to the alterations of hepatocyte pathology. This review focuses on some of the progress of CPT-II inactivity on IMM with liver fatty accumulation as a possible novel pathogenesis for NAFLD in hepatocarcinogenesis.
Collapse
Affiliation(s)
- Min Yao
- Department of Medical Immunology, Medical School of Nantong University & Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Ping Zhou
- Department of Medical Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Yan-Yan Qin
- Department of Medical Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Li Wang
- Research Center for Intelligent Information Technology, Nantong University, Nantong 226019, Jiangsu Province, China
| | - Deng-Fu Yao
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| |
Collapse
|
|
10
|
Almalki DA. Hepatorenal Protective Effect of Fenugreek Aqueous Extract against Lead Toxicity in Experimental Rats. DOKL BIOCHEM BIOPHYS 2022; 507:318-325. [PMID: 36786994 DOI: 10.1134/s1607672922340014] [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: 09/10/2022] [Revised: 10/20/2022] [Accepted: 10/20/2022] [Indexed: 02/15/2023]
Abstract
In this study, aqueous extract of germinated fenugreek seeds was investigated to assess its therapeutic effect on hepatorenal lead toxicity in experimental rats. After overnight fasting, rats were injected intraperitoneally with 0.5 mL of lead acetate at a dose of 35 mg/kg body weight for five consecutive days. Animals were divided into four groups of ten rats each: normal control; untreated negative control and rats treated with 200 or 400 mg/kg body weight of the aqueous extract. Treatments were performed by intraperitoneal injection of 1mL of the extract once a day for 28 consecutive days. Results showed significant differences between treated and control groups during the whole period of the experiment. This was demonstrated by improving body weight and level of serum total protein, decreasing levels of serum ALT, AST, total bilirubin, blood urea nitrogen, and creatinine. As well, histological analysis revealed a marked reduction in inflammation and structural alterations of liver and kidney organs of fenugreek-treated rats. This hepatoprotective effect can be attributed to the anti-inflammatory, anti-oxidant and regenerative capacity of the high content of the phytochemical constituents in the extract.
Collapse
Affiliation(s)
- D A Almalki
- Biology Department, Faculty of Science and Arts in Qilwah, Albaha University, Qilwah, Saudi Arabia.
| |
Collapse
|
|
11
|
Oh H, Park CH, Jun DW. Impact of l-Carnitine Supplementation on Liver Enzyme Normalization in Patients with Chronic Liver Disease: A Meta-Analysis of Randomized Trials. J Pers Med 2022; 12:jpm12071053. [PMID: 35887550 PMCID: PMC9322040 DOI: 10.3390/jpm12071053] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Revised: 06/21/2022] [Accepted: 06/24/2022] [Indexed: 11/22/2022] Open
Abstract
The effectiveness of l-carnitine in chronic liver disease remains controversial. We conducted this meta-analysis to assess the efficacy of various forms of l-carnitine in the treatment of chronic liver disease. Methods: We searched the Cochrane Library, EMBASE, KMBASE, and Medline databases for all relevant studies published until April 2022 that examined the ability of l-carnitine or its derivatives to normalize liver enzymes in patients with chronic liver disease. We performed meta-analyses of the proportion of patients with alanine aminotransferase (ALT) normalization and post-treatment serum aspartate aminotransferase (AST) and ALT levels. A random effects model was used for meta-analyses. Results: Fourteen randomized controlled trials (1217 patients) were included in this meta-analysis. The proportion of patients in whom ALT normalized was higher in the carnitine-orotate treatment group than in the control group (pooled odds ratio (OR), 95% confidence interval (CI) = 4.61 (1.48–14.39)). The proportion of patients in whom ALT normalized was also higher among those who received the carnitine-orotate complex, a combination of carnitine-orotate, biphenyl dimethyl dicarboxylate, and other minor supplementary compounds than in those who did not without significant heterogeneity (pooled OR (95% CI) = 18.88 (7.70–46.27); df = 1; p = 0.51; I2 = 0%). l-carnitine supplementation effectively lowered serum ALT levels compared to controls (pooled mean difference (95% CI) = −11.99 (−22.48 to −1.49)). Conclusions: l-carnitine supplementation significantly lowered ALT and AST levels and normalized ALT levels in patients with chronic liver disease.
Collapse
Affiliation(s)
- Hyunwoo Oh
- Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu 11690, Korea;
| | - Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri 11923, Korea
- Correspondence: (C.H.P.); (D.W.J.); Tel.: +82-31-560-2230 (C.H.P.); +82-2-2290-8338 (D.W.J.)
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul 04763, Korea
- Correspondence: (C.H.P.); (D.W.J.); Tel.: +82-31-560-2230 (C.H.P.); +82-2-2290-8338 (D.W.J.)
| |
Collapse
|
|
12
|
Selected Organ and Endocrine Complications According to BMI and the Metabolic Category of Obesity: A Single Endocrine Center Study. Nutrients 2022; 14:nu14061307. [PMID: 35334964 PMCID: PMC8954480 DOI: 10.3390/nu14061307] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 03/16/2022] [Accepted: 03/17/2022] [Indexed: 02/01/2023] Open
Abstract
Obesity is a chronic and complex disease associated with metabolic, organ and endocrine complications. In the study, we analyzed a group of 105 patients suffering from obesity without any other previously recognized serious disorders who had been referred to a single endocrine center. The study aimed to assess the prevalence of selected organ and endocrine complications by subdividing the group, firstly according to body mass index (BMI) and secondly with regard to metabolic syndrome (MetS), pre-MetS and the metabolically healthy obesity (MHO) category. We have observed that in our groups, the prevalence of hyperlipidemia, hypertension, asthma, obstructive sleep apnea (OSA) depended on BMI category, whereas the incidence of hyperlipidemia, hypertension, OSA, hypothyroidism, non-alcoholic fatty liver disease, prediabetes, and type 2 diabetes was related to the metabolic category. We concluded that the distribution of particular organ and endocrine complications change significantly with increased BMI and with the shift from MHO to pre-MetS and MetS. Thus, to determine the risk of organ and endocrine complications more effectively, BMI and metabolic status should be assessed during the examination of patients with obesity.
Collapse
|
|
13
|
Ma Q, Liao X, Shao C, Lin Y, Wu T, Sun Y, Feng ST, Ye J, Zhong B. Normalization of γ-glutamyl transferase levels is associated with better metabolic control in individuals with nonalcoholic fatty liver disease. BMC Gastroenterol 2021; 21:215. [PMID: 33971815 PMCID: PMC8112063 DOI: 10.1186/s12876-021-01790-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Accepted: 04/26/2021] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND The normalization of liver biochemical parameters usually reflects the histological response to treatment for nonalcoholic fatty liver disease (NAFLD). Researchers have not clearly determined whether different liver enzymes exhibit various metabolic changes during the follow-up period in patients with NAFLD. METHODS We performed a retrospective analysis of patients with NAFLD who were receiving therapy from January 2011 to December 2019. Metabolism indexes, including glucose levels, lipid profiles, uric acid levels and liver biochemical parameters, were measured. Magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) and liver ultrasound were used to evaluate steatosis. All patients received recommendations for lifestyle modifications and guideline-recommended pharmacological treatments with indications for drug therapy for metabolic abnormalities. RESULTS Overall, 1048 patients with NAFLD were included and received lifestyle modification recommendations and pharmaceutical interventions, including 637 (60.7%) patients with abnormal GGT levels and 767 (73.2%) patients with abnormal ALT levels. Patients with concurrent ALT and GGT abnormalities presented higher levels of metabolism indexes and higher liver fat content than those in patients with single or no abnormalities. After 12 months of follow-up, the cumulative normalization rate of GGT was considerably lower than that of ALT (38% vs. 62%, P < 0.001). Greater weight loss resulted in higher cumulative normalization rates of GGT and ALT. Weight loss (OR = 1.21, 95% CI 1.11-1.32, P < 0.001), ALT normalization (OR = 2.75, 95% CI 1.41-5.36, P = 0.01) and lower TG and HOMA-IR values (OR = 2.03, 95% CI 1.11-3.71, P = 0.02; OR = 2.04, 95% CI 1.07-3.89, P = 0.03) were independent protective factors for GGT normalization. Elevated baseline GGT (OR = 0.99, 95% CI 0.98-0.99, P = 0.01) was a risk factor. CONCLUSIONS For NAFLD patients with concurrently increased ALT and GGT levels, a lower normalization rate of GGT was observed, rather than ALT. Good control of weight and insulin resistance was a reliable predictor of GGT normalization.
Collapse
Affiliation(s)
- Qianqian Ma
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, China
| | - Xianhua Liao
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, China
| | - Congxiang Shao
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, China
| | - Yansong Lin
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, China
| | - Tingfeng Wu
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, China
| | - Yanhong Sun
- Department of Clinical Laboratories, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Shi-Ting Feng
- Department of Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Junzhao Ye
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, China.
| | - Bihui Zhong
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, China.
| |
Collapse
|
|
14
|
Zhang L, Zhou X, Dai Y, Lv C, Wu J, Wu Q, Li T, Wang Y, Xia P, Pei H, Huang B. Establishment of interleukin-18 time-resolved fluorescence immunoassay and its preliminary application in liver disease. J Clin Lab Anal 2021; 35:e23758. [PMID: 33720453 PMCID: PMC8128310 DOI: 10.1002/jcla.23758] [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: 11/06/2020] [Revised: 02/01/2021] [Accepted: 02/27/2021] [Indexed: 12/30/2022] Open
Abstract
Background To establish a time‐resolved fluorescence immunoassay of interleukin (IL)‐18 (IL‐18‐TRFIA) and detect its concentration in different liver disease serum samples. Methods The IL‐18 coating antibody and the Eu3+‐labeled detection antibody were used for the IL‐18‐TRFIA to detect serum IL‐18 concentration in patients with liver cancer, hepatitis B, hepatitis C, autoimmune hepatitis, fatty liver disease, and healthy controls. The double‐antibody sandwich method was used and methodological evaluation was performed. Results The average intra‐ and inter‐assay coefficient of variation for IL‐18‐TRFIA was 4.80% and 5.90%, respectively. The average recovery rate was 106.19 ± 3.44%. The sensitivity (10.96 pg/mL) was higher than that obtained using the ELISA method (62.5 pg/mL). The detection range was 10.96–1000 pg/mL. IL‐6 and galectin‐3 did not cross‐react with IL‐18‐TRFIA. The serum concentration of IL‐18 was (776.99; 653.48–952.39 pg/mL) in hepatitis C, (911; 775.55–1130.03 pg/mL) in fatty liver, (1048.88; 730.04–1185.10 pg/mL) in liver cancer, and (949.12; 723.70–1160.28 pg/mL) in hepatitis B. Moreover, IL‐18 serum levels were significantly higher in patients than the healthy controls (483.09; 402.52–599.70/mL) (p < 0.0001). Autoimmune hepatitis with a serum IL‐18 concentration of 571.62; 502.47–730.31 pg/mL was not significantly different from the healthy controls (p > 0.05). Conclusion We established a highly sensitive IL‐18‐TRFIA method that successfully detected serum IL‐18 concentrations in different liver diseases. Furthermore, IL‐18 serum concentration was higher in patients with liver cancer, hepatitis C, hepatitis B, and fatty liver disease compared to healthy controls.
Collapse
Affiliation(s)
- Li Zhang
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Xiumei Zhou
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Yaping Dai
- Wuxi No. 5 People's Hospital, Wuxi, China
| | - Chunyan Lv
- Wuxi No. 5 People's Hospital, Wuxi, China
| | - Jian Wu
- Department of Laboratory Medicine, The First People's Hospital of Yancheng City, Yancheng, China
| | - Qingqing Wu
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Ting Li
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Yigang Wang
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Penguo Xia
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Hao Pei
- Wuxi No. 5 People's Hospital, Wuxi, China
| | - Biao Huang
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| |
Collapse
|