Hepatoprotective effects of N-acetylcysteine on liver injury by irisin upregulation and oxidative stress reduction in diabetic rats

Abstract

Background: The current study aimed to investigate the oxidative stress in rat liver with diabetes mellitus (DM) 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-day regimens of experimental or control groups. NAC-treated group is as follows: 100 mg/kg once daily was administered intraperitoneally (i.p.). Diabetes-induced group is as follows: single-dose intraperitoneal injection of streptozotocin (STZ) (50 mg/kg) was used to induce DM in overnight fasting Wistar rats. By determining blood glucose concentration in STZ-induced rats 72 h after injection of STZ, DM was assessed. DM + NAC group is as follows: STZ-induced DM plus NAC is described previously. On the 30th day of the experiment, liver samples were collected after fasting and anesthesia. Biochemical analyses were performed to measure total antioxidant status (TAS), total oxidant status (TOS), and malondialdehyde (MDA) levels. Each liver sample was weighed and 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 damage was detected as oxidative stress, increased irisin immunoreactivity, sinusoidal dilatation, and hepatocyte degeneration. In the DM + NAC group, it was observed that NAC significantly reduced the aforementioned histopathological changes due to STZ. 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.