Protective effect of rutin against carbon tetrachloride-induced oxidative stress, inflammation and apoptosis in mouse kidney associated with the ceramide, MAPKs, p53 and calpain activities

Abstract

Rutin, a natural flavonoid, possess beneficial health effects. However, its renoprotective effect against carbon tetrachloride (CCl₄) induced injury and the underlying mechanism is not clarified. The current study aims is to identify the therapeutic effects of rutin on oxidative stress, inflammation and apoptosis in mouse kidney exposed to CCl₄. ICR mice received CCl₄ with or without rutin co-administration for one week. Compared with the control group, mice receiving CCl₄ alone showed kidney injury as evidenced by elevation in serum biochemical markers, inflammation, caspase-3 activity and apoptosis in kidney, while rutin administration significantly attenuated these pathophysiological changes. Exploration of the underlying mechanisms of its action demonstrated that rutin reduced the ROS, calpain and ceramide levels in mouse kidneys. Rutin significantly decreased the p53, TNF-α, IL-1β activities and mitogen-activated protein kinase (MAPK) phosphorylation in the kidneys. In addition, rutin increased the levels of Bcl-2 protein and reduced levels protein of Bax. Rutin also inhibited the release of cytochrome C from mitochondria in kidneys of the CCl₄-treated mice. Taken together, rutin ameliorates CCl₄-induced oxidative stress, inflammation and apoptosis through regulating the ceramide, MAPK, p53 and calpain activities and thereby suppressing apoptosis by the mitochondrial pathway.

Keywords: Apoptosis; CCl(4); Inflammation; Kidney; Oxidative stress; Rutin.