Hepatoprotective effects of gentisic acid through its anti-oxidant properties in nicotinamide-streptozotocin induced diabetic mice

Type 2 diabetes mellitus (T2DM) is a common metabolic disorder that causes many complications. Liver failure is one of the complications of T2DM. Oxidative stress plays a major role in the development and progression of T2DM-induced liver injury. Gentisic acid (GA) is a metabolite of aspirin and also a phenolic compound found in natural sources that is a highly effective antioxidant and free radical scavenger. So, in this study, the potential preventive benefits of GA against liver damage induced by T2DM were explored. This study was conducted on 24 adult male mice. T2DM was induced by intraperitoneal injection of a single dose of streptozotocin (at a dose of 65 mg/kg), 15 min after the injection of nicotinamide (at a dose of 120 mg/kg). The grouping was as follows: 1) Normal Control Group; 2) Diabetic Control Group; 3) Positive Control Group: received metformin (150 mg/kg body weight daily) through gavage; 4) Treatment Group: received GA at the dose of 100 mg/kg body weight daily through gavage. Treatments continued for two weeks. Two weeks of GA treatment in diabetic mice reduced fasting blood glucose, improved plasma levels of hepatic enzymes, and increased liver tissue antioxidant capacity. Histopathological examination revealed that GA administration reduced diabetes-induced liver damage. Furthermore, GA treatment led to the down-regulation of Kelch-like ECH-associated protein 1 (Keap1) and up-regulation of nuclear factor E2-related factor 2 (Nrf2). The results of this study showed that GA exerts hepatoprotective effects in STZ-induced T2DM mice.