Elevated oxidative stress in type 2 diabetic OLETF rat liver

Abstract

PurposeTo investigate the oxidative stress level at the initial stage of diabetes in Otsuka Long‐Evans Tokushima Fatty (OLETF) rat liver.MethodsMale OLETF rats, which are used as an animal model of type 2 diabetes, and their counterparts (Long‐Evans Tokushima Otsuka [LETO] rats) were studied (n = 4, respectively). Liver samples were collected from 25‐week‐old rats under anesthesia following an overnight fast. Reduced and oxidized glutathione (GSH and GSSG, respectively) and thiobarbituric acid reatctive substance (TBARS) concentrations were measured. Glutathione reductase (GR) and glutathione peroxidase (GPx) mRNA levels were analyzed by RT‐PCR. Protein carbonylation was analyzed in cytosolic and mitochondrial fractions by Western blotting.ResultsThere were no differences in GSH concentration and GR mRNA level between the animals. In contrast, the TBARS and GSSG concentrations and GPx mRNA expression level were significantly higher in the OLETF rats (+82.9%, +31.1% and +100.4%, respectively) than in LETO rats (p < 0.05). The protein carbonylation level in the mitochondrial fraction was significantly higher in OLETF rats (+19.6%) than in LETO rats (p < 0.05), whereas no difference in the protein carbonylation level in the cytosolic fraction were observed between the animals.ConclusionOur data suggest that oxidative stress increases in the OLETF rat liver at the initial stage of type 2 diabetes.