Melatonin and vitamin E attenuate acetamiprid induced hepatic injury in male mice

Acetamiprid (ACMP), a neonicotinoid insecticide widely used in agriculture, induces systemic toxicity via oxidative stress. This study investigated the potential protective effects of Melatonin (Mel) and Vitamin E (Vit E) against ACMP-induced hepatotoxicity using biochemical, histopathological and ultrastructural analyses. Fifty mice were divided into experimental groups, including control and treatment cohorts. ACMP was administered to induce liver injury. The therapeutic groups received Mel and Vit E either alone or in combination. Hepatotoxicity was assessed using serum liver enzymes (ALT, AST and ALP) and oxidative stress markers (MDA, GSH, SOD, CAT, TAS and TOS). Structural changes were evaluated using hematoxylin and eosin (H&E) and Masson’s trichrome staining, while subcellular integrity was examined via transmission electron microscopy (TEM). Apoptotic activity was determined using immunohistochemistry for Caspase-3. ACMP administration significantly elevated serum ALT, AST and ALP levels, inducing severe oxidative stress, characterized by elevated MDA and TOS levels and reduced antioxidant capacity. Histopathological examination revealed extensive parenchymal necrosis, inflammatory infiltration and pericentral fibrosis in the ACMP group. TEM analysis corroborated these findings by revealing mitochondrial cristolysis and endoplasmic reticulum dilatation. Furthermore, ACMP significantly increased Caspase-3 expression, indicating robust apoptotic activation. Among the treatment groups, combined Mel and Vit E administration was associated with the greatest normalization of the measured biochemical markers, lower Caspase-3 immunoreactivity and better-preserved histopathological and ultrastructural morphology. These findings indicate that the combined regimen attenuated ACMP-associated hepatic injury in this mouse model.