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Published on:24th Feb,2014
Free Radicals and Antioxidants, 2014; 4(1):32-38
Original Article | doi:10.5530/fra.2014.1.6

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


Authors and affiliation (s):

Ramadan A. M. Hemeida1 Ihab T. Abdel-Raheem2* Gamal A. El-Sherbiny3 El-Shaimaa A. Arafa4, Abdel-Gawad S. Abdel-Gawad1

1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt

2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Damanhour University, Egypt

3Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kafr El-Sheikh University, Egypt

4Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Egypt

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.

Key words: Fibrosis, Angiotensin II, TNF-α, Oxidative Stress.

 

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