Glycyrrhizic acid inhibits apoptosis and fibrosis in carbontetrachloride-induced rat liver injury

AIM: To investigate anti-apoptotic effects of glycyrrhizic acid (GA) against fibrosis in carbon tetrachloride (CCl₄)-induced liver injury and its contributing factors.METHODS: Liver fibrosis was induced by administration of CCl₄ for 8 wk. Pathological changes in the liver of rats were examined by hematoxylin-eosin staining. Collagen fibers were detected by Sirius red staining. Hepatocyte apoptosis was determined by TUNEL assay and the expression levels of cleaved caspase-3, Bax, α-SMA, connective tissue growth factor (CTGF), matrix metalloproteinase (MMP) 2 and MMP9 proteins were evaluated by western blot analysis, and α-SMA mRNA, collagen type I and III mRNA were estimated by real-time PCR.RESULTS: Treatment with GA significantly improved the pathological changes in the liver and markedly decreased the positive area of Sirius red compared with rats in the CCl₄-treated group. TUNEL assay showed that GA significantly reduced the number of TUNEL-positive cells compared with the CCl₄-treated group. The expression levels of cleaved caspase-3, Bax, α-SMA, CTGF, MMP2 and MMP9 proteins, and α-SMA mRNA, collagen type I and III mRNA were also significantly reduced by GA compared with the CCl₄-treated group (P < 0.05).CONCLUSION: GA treatment can ameliorate CCl₄-induced liver fibrosis by inhibiting hepatocyte apoptosis and hepatic stellate cell activation.