Protective Effect of Grape Seed Extract and/or Silymarin Against Thioacetamide-induced Hepatic Fibrosis in Rats

The aim of the present study was designed to evaluate the hepatoprotective and antioxidant potentials of GSE (100 and 200 mg/kg) and/or silymarin against TAA-induced liver fibrosis in rats. This study was designed to investigate the protective effect of grape seed extract (GSE) and/or silymarin against thioacetamide (TAA)-induced hepatic fibrosis in Sprague-Dawley rats. Mature male Sprague-Dawley rats were divided into 7 equal groups (8 rats each) and treated as follows: Group 1, kept as control group and orally given saline; groups 2-7 were injected intraperitoneally (i.p.) with TAA (100 mg/Kg) twice weekly for 6 weeks to induce hepatic fibrosis. Group 2, kept as control positive; groups 3-5 were administered daily oral doses of silymarin (50 mg/kg), GSE (100 mg/kg) and GSE (200 mg/kg), respectively. While groups 6-7 were administered combined treatments of silymarin and GSE (100 mg/kg) or GSE (200 mg/kg), respectively. Our results indicated that TAA caused significant elevation of hydroxyproline (Hyp), malondialdehyde (MDA) and nitric oxide (NO) contents in liver homogenate and increased serum levels of: aminotransferases (AST and ALT), alkaline phosphatase (ALP) and total bilirubin. While, TAA-treatment alone significantly decreased serum total protein and reduced glutathione (GSH) content in liver homogenate. Administration of GSE (100 and 200 mg/kg) and/or silymarin attenuated TAA-induced hepatic fibrosis, improved enzymes and reduced the oxidative stress in dose dependant manner Histopathological study showed disruption of the hepatic architecture and collagen fibers deposition in the portal tract of TAA-injected group. Concomitant treatment with GSE (100 and 200 mg/kg) and/or silymarin significantly improved histopathological structure of liver tissue in variable degrees. In conclusion, the combined effect of GSE (200 mg/kg) with silymarin (50 mg/kg) had powerful hepatoprotective effect than any other studied doses.