DOSE-DEPENDENT PROTECTIVE EFFECTS OF IRISIN AGAINST BISPHENOL A-INDUCED OXIDATIVE STRESS AND CASPASE-3-MEDIATED APOPTOSIS IN AML12 HEPATOCYTES

Bisphenol A (BPA) is a widespread environmental contaminant that causes hepatotoxicity through oxidative stress and apoptosis. In the present study, the dose-dependent protective effect of irisin against BPA-induced hepatotoxicity in AML12 hepatocytes was evaluated. AML12 hepatocytes were treated with BPA (100 µM) with or without irisin (50 and 100 nM). Cell viability was measured by MTT test and cytotoxicity was measured by lactate dehydrogenase (LDH) release. The oxidative status of the cells was characterized by evaluating malondialdehyde (MDA) levels, total oxidant status (TOS), total antioxidant status (TAS), and superoxide dismutase (SOD) activity. In addition, the oxidative stress index (OSI) and caspase-3 activity were assessed to provide insight into cellular redox balance and apoptotic responses. BPA significantly reduced cell viability and antioxidant capacity, and increased LDH release, lipid peroxidation and apoptotic activity. However, irisin significantly ameliorated these changes in a dose-dependent manner. More specifically, irisin significantly decreased MDA, TOS, OSI, and caspase-3 activity and increased SOD activity and TAS levels, and cell viability. The higher dose of irisin (100 nM) was more effective than the lower dose. This study found that irisin alleviated BPA-induced hepatotoxicity by mitigating oxidative stress and caspase-3-mediated apoptosis, implying that irisin may represent a potential therapeutic candidate for the treatment of toxin-induced liver injury.