Nicorandil attenuates lithocholic acid-induced hepatotoxicity in mice through impeding oxidative stress, inflammation and apoptosis

Abstract

This study was performed to explore the beneficial protective impact of nicorandil (Nico) against lithocholic acid (LCA)-induced hepatotoxicity. Materials and methods: Mice received Nico (50 and 100 mg/kg. orally) for 7 days and LCA (125 mg/kg, i.p.) was injected for the last 4 days two times daily. Results: Nico improved both structural and functional abnormalities induced by LCA. Nico significantly decreased serum levels of transaminases, ALP, GGT and markedly elevated albumin levels. Additionally, Nico mitigated oxidative stress; it decreased contents of MDA and NO and increased GSH level and SOD activity. Moreover, Nico markedly decreased the elevated levels of TNF-α, JNK, Bax, Caspase-3 and iNOS, and increased the levels of eNOS in hepatic tissues. Furthermore, Nico substantially decreased the expression of NFκBp65 in hepatic tissues. Histopathological and transmission electron microscopy findings further supported these biomarkers. Conclusion: Nico might be used as an adjuvant medication to prevent LCA-induced hepatotoxicity, pending further clinical research, through impeding oxidative stress, inflammation and apoptosis.