In Vitro and In Vivo Experimental Hepatotoxic Models in Liver Research: Applications to the Assessment of Potential Hepatoprotective Drugs

Farghali, Hassan; Kemelo, Mighty Kgalalelo; Wojnarová, L; Canová, Nikolina Kutinová

doi:10.33549/physiolres.933506

Cited by 36 publications

(21 citation statements)

References 39 publications

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“…The liver is an organ in which there are anatomical and physiological alterations due to the presence of the signs that comprise the MS. One of these alterations is fatty liver and, in this condition, the organ shows inflammation, fibrosis, ROS accumulation, OS, LPO, carbonylation, and changes in the activities of the antioxidant enzymes [19]. A better understanding regarding the pathogenesis of fatty liver in the MS and of the underlying OS that causes it is needed to develop new possible treatments.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol and Quercetin Administration Improves Antioxidant DEFENSES and reduces Fatty Liver in Metabolic Syndrome Rats

et al. 2019

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Mixtures of resveratrol (RSV) + quercetin (QRC) have antioxidant properties that probably impact on fatty liver in metabolic syndrome (MS) individuals. Here, we study the effects of a mixture of RSV + QRC on oxidative stress (OS) and fatty liver in a rat model of MS. Weanling male Wistar rats were separated into four groups (n = 8): MS rats with 30% sucrose in drinking water plus RSV + QRC (50 and 0.95 mg/kg/day, respectively), MS rats without treatment, control rats (C), and C rats plus RSV + QRC. MS rats had increased systolic blood pressure, triglycerides, insulin levels, insulin resistance index homeostasis model (HOMA), adiponectin, and leptin. The RSV + QRC mixture compensated these variables to C values (p < 0.01) in MS rats. Lipid peroxidation and carbonylation were increased in MS. Total antioxidant capacity and glutathione (GSH) were decreased in MS and compensated in MS plus RVS + QRC rats. Catalase, superoxide dismutase isoforms, peroxidases, glutathione-S-transferase, glutathione reductase, and the expression of Nrf2 were decreased in MS and reversed in MS plus RVS + QRC rats (p < 0.01). In conclusion, the mixture of RSV + QRC has benefic effects on OS in fatty liver in the MS rats through the improvement of the antioxidant capacity and by the over-expression of the master factor Nrf2, which increases the antioxidant enzymes and GSH recycling.

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Section: Discussionmentioning

confidence: 99%

Resveratrol and Quercetin Administration Improves Antioxidant DEFENSES and reduces Fatty Liver in Metabolic Syndrome Rats

et al. 2019

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“…C57BL (C57) and C57BL/10ScSn-Dmdmdx/J (mdx, a mouse model of dystrophinopathy) male mice aged 4-5 weeks were obtained from the Guangdong Medical Laboratory Animal Center (Guangzhou, GD, China) and the Model Animal Research Center of Nanjing University (Nanjing, JS, China), respectively. D-Galactosamine (D-GalN), an amino sugar resulting in depletion of uridine moieties within the liver and leading to hepatocyte necrosis, was chosen as an inducer of acute liver injury [ 23 , 24 ]. Mice were randomly divided into four groups: C57 NS, C57 D-GalN, mdx NS, and mdx D-GalN ( n = 10 each).…”

Section: Methodsmentioning

confidence: 99%

Ratio of Creatine Kinase to Alanine Aminotransferase as a Biomarker of Acute Liver Injury in Dystrophinopathy

Wang

Chen

et al. 2018

Disease Markers

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Objective To investigate the ratios of creatine kinase (CK) to aminotransferases as biomarkers of acute liver injury in dystrophinopathy. Methods C57 and mdx (dystrophic) mice were treated with a hepatotoxic reagent D-galactosamine (D-GalN). The degrees of liver and muscle injury were assessed using histological examinations. To examine whether serum CK-adjusted aminotransferase levels could indicate liver status in dystrophic mice, the CK/alanine aminotransferase (ALT) and CK/aspartate aminotransferase (AST) ratios were analyzed. Furthermore, we enrolled 658 male patients with dystrophinopathy and 378 male patients without muscle and liver injury as control, whose serum ALT, AST, and CK levels were examined. Results Animal experiments indicated that D-GalN treatment could induce acute liver injury but not muscle injury. Additionally, D-GalN decreased the CK/ALT and CK/AST ratios in both C57 mice and mdx mice (P < 0.001). However, there was an overlap of the CK/AST ratio between dystrophic mice with and without acute liver injury. In patients with dystrophinopathy, CK-adjusted ALT diminished the variability associated with age, genotype, clinical phenotype, and motor function (P > 0.05). Conclusions CK/ALT is a potential biomarker for the differential evaluation of acute liver injury in dystrophic mice, which highlights the value to further evaluate the practice of CK/ALT in dystrophinopathy patients.

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“…35 d-galactosamine plus lipopolysaccharide (d-GalN/LPS)induced liver damage is thought to be a good model to determine the effectiveness of hepatoprotective compounds. 36 Surgeries such as liver transplantation, partial hepatic resection and hepatic tumour resection may result in hepatic ischaemiareperfusion (IR) injury, which results in clinical reduction in liver function. Pretreatment of rats with OA (100 mg/kg, ip for 6 days) protected against hepatic IR injury.…”

Section: Low Dos E S Of Oa Protec T Ag Ain S T Hepatotoxi Cit Y Indmentioning

confidence: 99%

“…d ‐galactosamine plus lipopolysaccharide ( d ‐GalN/LPS)‐induced liver damage is thought to be a good model to determine the effectiveness of hepatoprotective compounds . Either oral OA (90 mg/kg, po) or OA injection (22.5 mg/kg, sc) for 4 days markedly protected against d ‐GalN/LPS hepatotoxicity.…”

Section: Low Doses Of Oa Protect Against Hepatotoxicity Induced By a mentioning

confidence: 99%

Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses

Liu

Lü

et al. 2018

Liver International

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Oleanolic acid (OA) is a triterpenoid that exists widely in fruits, vegetables and medicinal herbs. OA is included in some dietary supplements and is used as a complementary and alternative medicine (CAM) in China, India, Asia, the USA and European countries. OA is effective in protecting against various hepatotoxicants, and one of the protective mechanisms is reprogramming the liver to activate the nuclear factor erythroid 2-related factor 2 (Nrf2). OA derivatives, such as CDDO-Im and CDDO-Me, are even more potent Nrf2 activators. OA has recently been shown to also activate the Takeda G-protein-coupled receptor (TGR5). However, whereas a low dose of OA is hepatoprotective, higher doses and long-term use of OA can produce liver injury, characterized by cholestasis. This paradoxical hepatotoxic effect occurs not only for OA, but also for other OA-type triterpenoids. Dose and length of time of OA exposure differentiate the ability of OA to produce hepatoprotection vs hepatotoxicity. Hepatotoxicity produced by herbs is increasingly recognized and is of global concern. Given the appealing nature of OA in dietary supplements and its use as an alternative medicine around the world, as well as the development of OA derivatives (CDDO-Im and CDDO-Me) as therapeutics, it is important to understand not only that they program the liver to protect against hepatotoxic chemicals, but also how they produce hepatotoxicity.

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In Vitro and In Vivo Experimental Hepatotoxic Models in Liver Research: Applications to the Assessment of Potential Hepatoprotective Drugs

Cited by 36 publications

References 39 publications

Resveratrol and Quercetin Administration Improves Antioxidant DEFENSES and reduces Fatty Liver in Metabolic Syndrome Rats

Resveratrol and Quercetin Administration Improves Antioxidant DEFENSES and reduces Fatty Liver in Metabolic Syndrome Rats

Ratio of Creatine Kinase to Alanine Aminotransferase as a Biomarker of Acute Liver Injury in Dystrophinopathy

Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses

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