ArticleScientific reports2016
The enhanced atorvastatin hepatotoxicity in diabetic rats was partly attributed to the upregulated hepatic Cyp3a and SLCO1B1.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Coenzyme Q10 protects against atorvastatin-induced hepatotoxicity via attenuation of oxidative stress and functional modulation of CYP3A1.BMC pharmacology & toxicology · 2026Article
- Cytochrome P450 3A gene family in gastric cancer: Unveiling diagnostic biomarkers and therapeutic targets for personalized treatment.World journal of clinical oncology · 2025Review
- Pharmacokinetic interaction between regorafenib and atorvastatin in rats.Pharmacological reports : PR · 2024Article
- Autonomous circadian rhythms in the human hepatocyte regulate hepatic drug metabolism and inflammatory responses.Science advances · 2024Article
- Repurposing of the Cardiovascular Drug Statin for the Treatment of Cancers: Efficacy of Statin-Dipyridamole Combination Treatment in Melanoma Cell Lines.Biomedicines · 2024Article
- Sesamol combats diabetogenic effects of atorvastatin through GLUT-4 expression and improved pancreatic viability.3 Biotech · 2023Article
- Acetylsalicylic Acid Suppresses Alcoholism-Induced Cognitive Impairment Associated with Atorvastatin Intake by Targeting Cerebral miRNA155 and NLRP3: In Vivo, and In Silico Study.Pharmaceutics · 2022Article
- Machine Learning to Identify Interaction of Single-Nucleotide Polymorphisms as a Risk Factor for Chronic Drug-Induced Liver Injury.International journal of environmental research and public health · 2021Article
- Atorvastatin Induces FXR and CYP7A1 Activation as a Result of the Sequential Action of PPARγ/PGC-1α/HNF-4α in Hep3B Cells.The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi · 2021Article
- Potential Alteration of Statin-Related Pharmacological Features in Diabetes Mellitus.BioMed research international · 2021Review
- Hepatic Ischemia-Reperfusion Impairs Blood-Brain Barrier Partly Due to Release of Arginase From Injured Liver.Frontiers in pharmacology · 2021Article
- Effect of Rooibos (Aspalathus linearis) extract on atorvastatin-induced toxicity in C3A liver cells.Journal of cellular physiology · 2020Article
- Pharmacokinetic Interaction between Sorafenib and Atorvastatin, and Sorafenib and Metformin in Rats.Pharmaceutics · 2020Article
- Imbalance of Drug Transporter-CYP450s Interplay by Diabetes and Its Clinical Significance.Pharmaceutics · 2020Review
- Effects ofPharmaceutical biology · 2019Article
- Current trends in drug metabolism and pharmacokinetics.Acta pharmaceutica Sinica. B · 2019Review
- Improving Drug Discovery by Nucleic Acid Delivery in Engineered Human Microlivers.Cell metabolism · 2019Article
- Effects of Danshen tablets on pharmacokinetics of atorvastatin calcium in rats and its potential mechanism.Pharmaceutical biology · 2018Article
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Authors and funding
13 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Liver injury is a common adverse effect of atorvastatin. This study aimed to investigate atorvastatin-induced hepatotoxicity in diabetic rats induced by high-fat diet combined with streptozotocin. The results showed that 40 mg/kg atorvastatin was lethal to diabetic rats, whose mean survival time was 6.2 days. Severe liver injury also occurred in diabetic rats treated with 10 mg/kg and 20 mg/kg atorvastatin. The in vitro results indicated that atorvastatin cytotoxicity in hepatocytes of diabetic rats was more severe than normal and high-fat diet feeding rats. Expressions and activities of hepatic Cyp3a and SLCO1B1 were increased in diabetic rats, which were highly correlated with hepatotoxicity. Antioxidants (glutathione and N-Acetylcysteine), Cyp3a inhibitor ketoconazole and SLCO1B1 inhibitor gemfibrozil suppressed cytotoxicity and ROS formation in primary hepatocytes of diabetic rats. In HepG2 cells, up-regulations of CYP3A4 and SLCO1B1 potentiated hepatotoxicity and ROS generation, whereas knockdowns of CYP3A4 and SLCO1B1 as well as CYP3A4/SLCO1B1 inhibitions showed the opposite effects. Phenobarbital pretreatment was used to induce hepatic Cyp3a and SLCO1B1 in rats. Phenobarbital aggravated atorvastatin-induced hepatotoxicity, while decreased plasma exposure of atorvastatin. All these findings demonstrated that the upregulations of hepatic Cyp3a and SLCO1B1 in diabetic rats potentiated atorvastatin-induced hepatotoxicity via increasing ROS formation.
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