Carnosine decreased oxidation and glycation products in serum and liver of high-fat diet and low-dose streptozotocin-induced diabetic rats.

Abstract

High-fat diet (HFD) and low-dose streptozotocin (STZ)-treated rats provide useful animal model for type II diabetes mellitus. Oxidative stress and advanced glycation end products (AGEs) play a role in the development of diabetic complications. Carnosine (CAR) has anti-oxidant and anti-glycating properties. We investigated the effects of CAR on oxidation and glycation products in HFD+STZ rats. Rats were fed with HFD (60% of total calories from fat) for 4weeks, and then a single dose of STZ (40mg/kg; i.p.) was applied. Rats with blood glucose levels above 200mg/dl were fed with HFD until the end of the 12th week. CAR (250mg/kg body weight; i.p.; five times a week) was administered to the rats for the last fourweeks. CAR significantly decreased serum triglyceride (TG) (57.7%), cholesterol (35.6%) levels and hepatic marker enzyme activities of HFD+STZ rats. It significantly reduced serum reactive oxygen species (ROS) (23.7%), AGEs (13.4%) and advanced oxidized protein products (AOPP) (35.9%) and hepatic TG (59%), ROS (26%), malondialdehyde (MDA) (11.5%), protein carbonyl (PC) (19.2%) and AGE (20.2%) levels. Liver steatosis and hepatocyte ballooning were also significantly reduced. However, CAR treatment did not alter serum glucose and blood glycated haemoglobin and hepatic anti-oxidant enzyme activities/mRNA expressions in HFD+STZ rats. Our results indicate that CAR decreased accumulation of oxidation and glycation products, such as MDA, AGE, AOPP and PC in the serum and liver and ameliorated hepatic dysfunction in HFD+STZ rats. This effect may be related to its anti-oxidative, anti-glycating, and anti-lipogenic potential.