Antifibrotic Effects of Quercetin and Adenosine Deaminase Inhibitor on Thioacetamide-Induced Liver Fibrosis Mediated By P53 and NF-Kβ Gene Expression

Potent hepatotoxic chemicals such as thioacetamide (TAA) are used to evaluate hepatoprotective agents. Here we investigate the antifibrotic potential of quercetin (QU) as antioxidant and Erythro-9(2-hydroxy-3-nonyl) adenine (EHNA) as adenosine deaminase inhibitor against thioacetamideinduced liver fibrosis in male rats. Fifty mature male rats divided into 5 groups: Group I: served as a control was intraperitoneally (IP) injected with Dimethyl sulfoxide (DMSO) by 0.5 ml/rat. Group II: rats were injected IP with TAA (200 mg/kg) twice a week for 3 months. Group III: rats were injected IP with QU (100 mg/kg) 30 min before TAA injection Group IV: rats were injected IP with EHNA (150 μM/kg) 30 min before TAA injection. Group V: rats were injected IP with QU (100 mg/kg) and EHNA (150 μM/kg) 30 min before TAA injection. TAA administration causes hepatic necrosis, increases in liver function enzymes, increases in hepatic lipid peroxidation, decrease in glutathione level and increase in the gene expression of tumor protein (P53) and Nuclear Factor-kappa Beta (NF-kβ). With administration of QU alone, EHNA alone or the combination of both significantly attenuated liver fibrosis induced by TAA through decrease of liver biomarkers, improving the redox state of the tissue as well as hindered the expression of inflammation and apoptosis-related genes. Finally, it can be concluded that QU alone, EHNA alone or the combination of both have protective effects against TAA-induced hepatic fibrosis.