Melatonin prevents nicotine-induced hepatotoxicity by modulating apoptosis and histopathological changes in rats.

Nicotine, the main toxic component of tobacco, directly or indirectly causes adverse effects on the liver metabolism. Melatonin, secreted by the pineal gland, has anti-apoptotic activity as well as antioxidant activity. The aim of this study was to reveal the antiapoptotic effects of melatonin in rats with experimentally induced chronic liver damage with nicotine. In this study, 32 male Wistar albino rats were divided into four groups: control, melatonin, nicotine and nicotine+melatonin. During the experiment, nicotine (1 mg/kg) and melatonin (10 mg/kg) were administered daily intraperitoneally for 56 days. At the end of the study, the liver tissues were taken for histopathological, immunohistochemical and molecular analysis. The administration of melatonin was determined to partially alleviate histopathological changes in the liver tissue induced by nicotine, such as hepatocyte degeneration, vascular dilatation and congestion, and leukocyte infiltration. It was observed that there was a significant decrease in Bax expression levels and a significant increase in Bcl-2 expression levels in the nicotine+melatonin group when compared to the injury group. On the other hand, it was determined that melatonin administration reduced the Bax/Bcl-2 ratio, which was significantly higher in the nicotine group compared to the other groups, to a level close to the control group. Additionally, as a result of immunohistochemical evaluation, it was observed that decreased Bax expression and increased Bcl-2 expression in hepatocytes in the nicotine+melatonin group were at a level close to the control group. Our results revealed that melatonin is a hepatoprotective and effective antioxidant by suppressing cell apoptosis and increasing the rate of healing after damage at both the immunohistochemical and molecular levels.