Hepatotoxic Effect of Oral Zinc Oxide Nanoparticles and the Ameliorating Role of Selenium in Rats: A histological, immunohistochemical and molecular study

•ZnO NPs disrupted the hepatic architecture, elevated the serum liver enzyme ALT, AST and ALP levels and caused dose-dependent decrease in the activity of the anti-oxidant enzymes.•ZnO-NPs administration caused dose-dependent increase in the area percent of the apoptotic protein bax and decrease in the area percent of the anti-apoptotic protein bcl2 immunreactivity.•ZnO-NPs induced JNK/p38MAPK and the STAT3 gene expression.•ZnO-NP-hepatotoxicity was reversed by selenium administration. Despite the emerging concerns about the hepatotoxic risks associated with Zinc oxide nanoparticles (ZnO NPs), yet, the morphological and molecular alterations associated with these extensively-used nanoparticles remain to be elucidated. Thus, the current study has been designed to analyze the effect of ZnO NPs on the hepatic histopathological and immunohistochemical changes, along with the modulation of the oxidative-stress induced JNK/p38MAPK and the STAT-3 signalling. The study also explored the potential protective role of selenium against those alterations. ZnO NPs disrupted the hepatic architecture, elevated the serum liver enzyme alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) levels and caused dose-dependent decrease in the activity of the antioxidant enzymes glutathione-peroxidase, superoxide dismutase and catalase along with an increase in the lipid peroxidation product malondialdehyde. ZnO NPs also increased the area of immune-reactivity of the apoptotic protein bax and decreased the area of immune-reactivity of the anti-apoptotic protein bcl2 together with augmentation of the hepatic caspase 3 gene expression. The role of selenium in ameliorating the hepatotoxicity, oxidative stress injury, and apoptosis induced by ZnO-NPs, along with its role in modulating the JNK/p38MAPK and the STAT-3 signalling and improving the histopathological hepatic changes, offers selenium as a promising adjunctive therapy in individuals subjected to high concentrations of ZnO NPs especially in cases of extensive occupational, medicinal and industrial exposure.