Protective Potential of Grape Seed Proanthocyandins Extract against Glivec (Imatinib Mesylate) Induced Liver Toxicity and Oxidative Stress in Male Rats

Objectives: Glivec (Imatinib mesylate) an antineoplastic chemotherapeutic agent used in the treatment of many types of cancer. The current study examines the hepatoprotective potential of grape seed proanthocyandins extract (GSPE) against Glivec induced oxidative stress and toxicity in male albino rats.

Materials and Methods: A total of 40 male albino rats were equally divided into four groups; group 1 was control, group 2 was GSPE group (rats received orally GSPE by stomach tube {50 mg/kg BW/twice a week} for four week), group 3 was Glivec group (rats were injected intraperitoneally with Glivec {1 mg /kg B W/twice a week} for four weeks) and group 4 was rats treated with GSPE plus Glivec for four weeks.

Results: LD50 was calculated for Glivec in rats (estimated at 598 mg/kg), presenting confidence limits between 588 and 612 mg/kg body weight. A significant increase in the liver TBARS and aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and γ-glutamyltransferase (GGT) activities in Glivec group when compared with the control group. On the other hand; a significant decrease in the serum albumin, globulin, total protein, liver superoxide dismutase activity (SOD), catalase (CAT), glutathione S-trasferase (GST) and reduced glutathione (GSH) levels in Glivec group when compared with the control group. Administration of GSPE with Glivec caused a protective and ameliorative effect against Glivec induced liver toxicity.

Conclusions: Treatment with GSPE has a promising role for ameliorating the oxidative stress and hepatic injury induced by Glivec.