This study was designed to investigate the potentially protective effects of
glycyrrhetinic acid (GA) and the role of
transcription factor nuclear factor-erythroid 2(NF-E2)-related factor 2 (Nrf2) signaling in the regulation of
Carbon Tetrachloride (CCl(4))-induced chronic
liver fibrosis in mice. The potentially protective effects of GA on CCl(4)-induced chronic
liver fibrosis in mice were depicted histologically and biochemically. Firstly, histopathological changes including regenerative nodules, inflammatory cell infiltration and
fibrosis were induced by CCl(4).Then, CCl(4) administration caused a marked increase in the levels of serum
aminotransferases (GOT, GPT), serum
monoamine oxidase (
MAO) and lipid peroxidation (MDA) as well as
MAO in the mice liver homogenates. Also, decreased nuclear Nrf2 expression,
mRNA levels of its target genes such as
superoxide dismutase 3 (SOD3),
catalase (CAT),
glutathione peroxidase 2 (GPX2), and activity of cellular
antioxidant enzymes were found after CCl(4) exposure. All of these phenotypes were markedly reversed by the treatment of the mice with GA. In addition, GA exhibited the
antioxidant effects in vitro by on FeCl(2)-ascorbate induced lipid peroxidation in mouse liver homogenates, and on DPPH scavenging activity. Taken together, these results suggested that GA can protect the liver from oxidative stress in mice, presumably through activating the nuclear translocation of Nrf2, enhancing the expression of its target genes and increasing the activity of the
antioxidant enzymes. Therefore, GA may be an effective hepatoprotective agent and viable candidate for treating
liver fibrosis and other oxidative stress-related diseases.