Possible mechanism of protective effect of melatonin against carbendazim-induced hepatotoxicity in mature male rats: histological, immunofluorescence, and biochemical evaluations.

This study investigated carbendazim (CBZ)-induced hepatic dysfunction and the mechanistic pathway regarding the protective effect of melatonin (MEL). Twenty-eight male rats were grouped as follows: Control, CBZ (150 mg kg^-1), MEL (20.00 mg kg^-1), and CBZ + MEL. The experiment was conducted for 60 days. Tissue samples were stained with Hematoxylin and Eosin and immuno-fluorescence methods to examine apoptotic pathway. Also, hepatic enzymes and miR-122 expression were evaluated. The findings indicated that the CBZ group exhibited an increase in degenerated hepatocytes, hyperemia of sinusoids, and leukocyte infiltration, accompanied by elevated levels of aspartate aminotransferase and alanine aminotransferase, as well as up-regulation of miR-122. Also, there was a significant increase in the fluorescence intensities of caspase-3 and Bax in the CBZ group, whereas a substantial reduction in the fluorescence intensity of Bcl-2 was recorded. In contrast, the simultaneous administration of MEL alongside CBZ was shown to be effective in improving histological structure, decreasing levels of aspartate aminotransferase and alanine aminotransferase, reducing the apoptosis index, and modulating the expression of miR-122 in comparison with the CBZ-only group. The increased expression of miR-122 noted in the CBZ group may correlate with an elevation in the immunoreactivity of apoptosis markers and alterations in liver architecture. Additionally, MEL seems to alleviate CBZ-induced hepatotoxicity by down-regulating miR-122 expression, diminishing the fluorescence intensity of caspase-3 and Bax, and enhancing the immunoreactivity of Bcl-2. Collectively, the regulation of miR-122 may serve as a potential mechanism by which MEL confers its protective effects against liver damage induced by CBZ.