<i>N</i> -acetyl cysteine and vitamin E attenuate acrylamide-induced hepatotoxicity via regulation of miRNA-34a and P53/Nrf2/SIRT 1 signaling pathways

The present study is aimed to evaluate the hepatoprotective role of <i>N</i>-acetyl cysteine (NAC) and vitamin E (VE), as potent antioxidants, against acrylamide (ACR)-induced hepatotoxicity via investigation of alterations in miRNA-34a, P53, Nrf2, and SIRT 1 hepatic expressions in addition to, changes in liver function tests, oxidative stress/antioxidant parameters, cytokines, histopathological analysis and immunohistochemical expressions of caspase 3. For this study, thirty-five male rats were randomly assigned into seven equal groups: group I (control), group II received ACR at dose 20 mg/kg b.wt., group III received NAC at dose 150 mg/kg b.wt., group IV received VE at a dose of 100 mg/kg b.wt., group V received NAC+ACR, group VI received VE+ACR and finally group VII received NAC+VE+ACR, for 28 days. ACR induced marked hepatic tissue damage as evident by severe alterations in hepatic biomarkers, in addition to histological and immunohistochemical pictures. This was accompanied by a significant elevation of hepatic MDA and apoptotic genes expressions, alteration in miRNA-34a and P53/Nrf2/SIRT1 pathway as well as cytokines. In contrast, marked depletion for antioxidant parameters was detected. These findings were confirmed with marked histological changes. Co-administration of NAC and VE significantly attenuated the hepatotoxic effects of ACR where liver parameters, oxidative status, genetic expressions, and liver histo-architecture were improved in comparison to ACR, NAC+ACR, and VE+ACR groups. NAC and/or VE had powerful antioxidants and could be used as an applicable hepatoprotective agent against oxidative damage mediated by ACR via regulation of miRNA-34a and P53/Nrf2/SIRT 1 signaling pathways.