Hepatoprotective Effects of N-acetylcysteine on Liver Injury by Irisin Upregulation and Oxidative Stress Reduction in Diabetic Rats

Abstract

Abstract Purpose; The current study aimed to investigate the oxidative stress in diabetic rat liver as well as the protective effects of N-acetylcysteine (NAC)on irisin expression. Methods; Twenty-eight male Wistar rats were divided into four groups, 7 rats in each group and 30-d regimens of experimental or control groups. NAC treated group: 100mg/kg once daily was administered intraperitoneally (i.p.). Diabetes-induced group: Single dose intraperitoneal injection of streptozotocin (STZ) (50mg/kg B.W.) was used to induce diabetes mellitus in overnight fasting Wistar rats. By determining blood glucose concentration in STZ-induced rats 72 hours after injection of STZ, diabetes was assessed. DM+NAC group: STZ-induced DM plus NAC as described previously. Serial and liver samples were collected on the 30-day and after overnight fasting. Biochemical analyses were performed to measure total antioxidant status (TAS), total oxidant status (TOS), and Malondialdehyde (MDA)levels. Each liver sample was weighed, then prepared for histopathologic evaluation by light microscopy. Results; There was a statistically significant decrease in TAS levels and an increase in TOS and MDA levels in the DM group compared to the control group. In contrast, TOS and MDA levels were found significantly decreased, and TAS levels increased in the serum and liver tissues of the DM+NAC group compared to the DM group. Liver samples were also used for histopathological examination using hematoxylin-eosin and immunohistochemical staining. STZ-induced liver injury via increasing oxidative stress, sinusoidal dilatation, degeneration of hepatocytes, and in irisin, and immunoreactivity. NAC significantly reduced the STZ-induced hepatotoxicity. Conclusion; In the early period of diabetes, due to the antioxidant properties of irisin related to the sudden response of liver tissue to oxidative stress, it is thought that the immunoreactivity in the tissue increases in the early period. As a result, NAC in diabetic rat liver tissue was found to suppress oxidative damage and irisin immunoreactivity.