Melatonin Mitigates Abamectin‐Induced Subacute Hematotoxicity and Hepato‐Renal Toxicity in Rats by Regulating Oxidative Stress, Inflammatory Responses, and Apoptosis

ABSTRACT Abamectin is a widely used pesticide due to its strong anthelmintic and insecticidal activity and has toxic effects on nontarget organisms. In this study, melatonin (10 mg/kg body weight), which has potent anti‐inflammatory, antiapoptotic, and antioxidant effects against subacute hepato‐renal toxicity of abamectin (0.5 mg/kg body weight) in rats, was evaluated for its potential to alleviate organ damage by biochemical, oxidative stress, immunohistochemical, histopathological, and cytopathological studies. In hepato‐renal tissues of abamectin‐treated rats, MDA and 8‐OHdG levels, total oxidant status, and oxidative stress index significantly increased. In contrast, endogenous antioxidant enzyme activities and total antioxidant status decreased significantly. A significant decrease in acetylcholinesterase activity, TNF‐α and caspase‐3 immunopositive cells, and interleukin‐17 levels were also detected in the tissues. Abamectin caused a substantial reduction in red blood cell, hemoglobin, hematocrit, and platelet counts and significantly increased white blood cell count. In addition, abamectin increased the activities of ALT, AST, ALP, and LDH, and the levels of total cholesterol, triglyceride, creatinine, uric acid, urea, and BUN, which are evaluated as biomarkers of blood hepato‐renal tissues. At the same time, it caused a decrease in the levels of total protein and albumin. In addition, these changing biochemical parameters are accompanied by cytopathological and histopathological changes in hepato‐renal tissues. However, exogenous melatonin supplementation reduced the oxidative stress caused by abamectin in rats and caused the pathological changes in hepato‐renal tissues to be observed more mildly. It also reversed the changes in blood parameters and hepato‐renal markers. In conclusion, this study suggests that exogenous melatonin supplementation may help significantly ameliorate abamectin‐induced hepato‐renal injury in rats through anti‐inflammatory, antioxidant, and antiapoptotic mechanisms.