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چکیده
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Abstract This study investigated carbendazim (CBZ)-induced hepatic dysfunction and the mechanistic pathway on the protective effect of melatonin (MEL). Twenty-eight male rats were grouped (n = 7) as follows: control, CBZ (150 mg/kg), MEL (20 mg/kg), and CBZ + MEL. The experiment was conducted for 60 days by gavage method. Tissue samples were stained with H&E and IHC 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 AST and ALT, as well as upregulation of miR-122. Additionally, 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 has been shown to be effective in improving histological structure, decreasing levels of AST and ALT, reducing the apoptosis index, and modulating the expression of miR-122 in comparison to 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 marker proteins and alterations in liver architecture. Additionally, MEL seems to alleviate CBZ-induced hepatotoxicity by downregulating 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.
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