Chimie médicale

Gallic Acid Attenuates Dimethylnitrosamine-induced Acute Liver Injury in Mice through Nrf2-mediated Induction of Heme Oxygenase-1 and Glutathione-s-transferase Alpha 3

Abstract

Shaohua Ma, Li Lv, Qian Lu, Yubing Li, Feng Zhang, Musen Lin, Dongyan Gao, Kexin Liu, Xiaofeng Tian and Jihong Yao

Gallic acid, a widely distributed phenolic acid present in various plant species, has been demonstrated to possess anti-inflammatory, antioxidant and anticarcinogenic properties. In this study, the protective effect of gallic acid on acute liver injury induced by dimethylnitrosamine in mice was investigated. We attempted to explore the molecular mechanism from a perspective of phase âÃ?â?¦¡ enzymes, which plays a crucial role in cellular defense against oxidative stress. Toxicant caused severe hepatic pathological damage and significant increase of serum transaminase levels. Hepatic lipid peroxidation and the glutathione depletion could also be observed after dimethylnitrosamine administration. Pretreatment of gallic acid at different doses could inhibit hepatic submassive necrosis and attenuate all the marker parameters in both serum and liver tissue. Administration of gallic acid was found to increase the expression level of heme oxygenase-1 (HO-1) and glutathione-s- transferase alpha 3 (GSTA3), thereby enhance the detoxication ability in liver tissue. The upregulation of phase âÃ?â?¦¡ enzymes is caused, at least in part, by the nuclear accumulation of Nrf2, a transcriptional factor which binds to the antioxidant response element of DNA and triggers the expression of phase âÃ?â?¦¡ enzymes. These findings provide further insight of hepatoprotection mediated by gallic acid.