The effects of pinealectomy and melatonin on bisphenol a diglycidyl ether (BADGE)-induced hepatotoxicity in rats: involvement of apoptotic, inflammatory, and oxidative mechanisms.

In this study, rats were deprived of melatonin by removing their pineal gland (PinX), and the effects of Bisphenol A Diglycidyl Ether (BADGE) on oxidative stress, inflammation, apoptosis, histopathology, liver cell count, and mean liver volume were investigated. Furthermore, the protective effects of melatonin against the potential toxic effects of BADGE were assessed through exogenous melatonin administration. Fortyeight rats were divided into 6 groups (n = 8): Sham PinX, Sham PinX+BADGE, Sham PinX+BADGE+Mel, PinX, PinX+BADGE, and PinX+BADGE+Mel. The rats' pineal glands were either removed or underwent sham surgery. BADGE was administered intraperitoneally to the Sham PinX+BADGE and PinX+BADGE groups, while BADGE and melatonin were administered to the Sham PinX+BADGE+Mel and PinX+BADGE+Mel groups over twenty-one days. At the end of the experiment, liver tissues were examined through biochemical, immunohistochemical, histopathological, and stereological methods. A 21-day exposure to BADGE caused oxidative stress, inflammation, and apoptosis in rat liver tissue. Additionally, the activity of antioxidant enzymes and total antioxidant capacity decreased, while total oxidant level significantly increased. It was also observed that these effects were worsened in post-PinX rats with melatonin deficiency. However, 21 days of melatonin treatment reversed BADGEinduced liver damage by reducing oxidative stress and inflammation, inhibiting apoptosis, and repairing liver cells. Stereological analysis showed that melatonin significantly restored both the hepatocyte number and the mean liver volume. Our histopathological findings may significantly contribute to understanding structural changes in liver tissue. Melatonin treatment showed protective effects against the toxicity caused by BADGE in the liver tissue of pinealectomized rats by balancing the oxidant/antioxidant levels and inhibiting the release of pro-inflammatory cytokines and apoptosis.