Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 7 No. 1 January 28, 2020 p.41-54
Original Article
Comparison of the liver findings after simvastatin-treatment between Spontaneously Diabetic Torii-Leprfa (SDT fatty) rats and Sprague-Dawley rats
  • Tadakazu Takahashi (Toxicology Research Lab., Central Pharmaceutical Research Institute, JAPAN TOBACCO INC. / 2Graduate School of Integrated Pharmaceutical and Nutritional Sciences, Graduate Program in Environmental Health Sciences, University of Shizuoka / tadakazu.takahashi@jt.com)
Tadakazu Takahashi 1) 2) , Yusuke Suzuki 1) , Naohito Yamada 1) , Kaoru Toyoda 1) , Keisuke Goda 1) , Katsunori Ryoke 1) , Chizuru Matsuura 1) , Akio Kobayashi 1) , Shoichiro Sugai 1) , Kayoko Shimoi 2)
1) Toxicology Research Lab., Central Pharmaceutical Research Institute, JAPAN TOBACCO INC. , 2) 2Graduate School of Integrated Pharmaceutical and Nutritional Sciences, Graduate Program in Environmental Health Sciences, University of Shizuoka
Keywords: SDT fatty rats, Type 2 diabetes, Hepatotoxicity, Glutathione, Simvastatin
Abstracts

One of the risk factors for drug-induced liver injury (DILI) is the diabetic state. Our previous investigation showed that liver injury after repeated oral dosing with allyl alcohol and carbamazepine was enhanced more in the Spontaneously Diabetic Torii-Leprfa (SDT fatty) rats than in the Sprague-Dawley (SD) rats. It was caused by lower hepatic detoxification due to depleted hepatic glutathione synthesis. This is because simvastatin, frequently used in diabetic patients, shows a positive high reaction in a GSH adduct assay in vitro although the GSH adduction is considered not to be a major metabolic pathway of simvastatin. Therefore, in the present study, effects of simvastatin-treatment on the liver were compared between the Sprague-Dawley (SD) rats and SDT fatty rats in order to obtain additional information to estimate the potential risk of DILI in the diabetic state. There were no effects with simvastatin on the liver in the SD or SDT fatty rats after 13-week oral dosing of simvastatin. These results indicate that simvastatin does not have potential to induce liver injury in diabetic state and are consistent with the reports for the clinical use of simvastatin in the diabetic patients.