Candesartan modulates the antioxidant effect of silymarin against CCl4-induced liver injury in rats

Abstract

Aim: Liver fibrosis represents the final common pathway of chronic hepatic inflammation. The efficiency of single drug is limited in liver fibrosis. Consequently, combined therapy is more effective than monotherapy. Therefore, the aim of this study was to investigate the preventive effect of candesatran (CAN), silymarin (SIL) and their combination in CCL₄-induced liver fibrosis. Methods: Rats were divided into five groups: Control, CCL₄-treated rats, CAN-treated rats (2 mg/kg/day, orally), SIL-treated rats (100 mg/kg/day, orally) and their combination (SIL+CAN)-treated rats. All groups were treated for 7 weeks. ALT, AST and GGT were determined in serum. TNF-α, oxidative stress parameters (MDA, GSH levels and SOD activity) and NO level were measured in liver tissue. Other liver tissues were examined histopathologically. Results: CCL₄ induced marked elevation of ALT, AST and GGT. Moreover, CCL₄ increased liver tissue of TNF-α, MDA and NO contents and decreased GSH level and SOD activity. Administration of either CAN or SIL significantly alleviated CCL₄- induced biochemical changes. On the other hand the combined administration of CAN with SIL has an ameliorative effect which is greater than each drug alone. Conclusion: The combination therapy between CAN and SIL is more effective than either drug alone which is attributed to augmentation of their antioxidant effects.