Objectives: This study evaluated the protective effects of gentisic acid (GA) against genotoxicity and hepatotoxicity induced by cyclophosphamide (CP) in Swiss albino mice.
Methods: Mice were pretreated with GA orally at doses of 50 and 100 mg/kg for 14 consecutive days before the administration of a single intraperitoneal dose of 50 mg/kg CP. The ameliorative effect of GA on genotoxicity was studied using the in-vivo bone marrow micronuclei induction test, DNA integrity and alkaline unwinding assay. The activity of various oxidative stress enzymes were estimated in hepatic tissue.
Key findings: A single intraperitoneal administration of CP in mice increased the malondialdehyde level, depleted the glutathione content and antioxidant enzyme activity (glutathione peroxidase, glutathione reductase, catalase and quinone reductase), and induced DNA strand breaks and micronuclei induction. Oral pretreatment with GA at both doses caused a significant reduction in malondialdehyde and glutathione levels, restoration of antioxidant enzyme activity, reduction in micronuclei formation and DNA fragmentation. Serum toxicity marker enzymes such as aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase were increased after CP treatment but restored in GA pretreated groups.
Conclusion: The results support the protective effect of GA against CP induced genotoxicity and hepatotoxicity.
© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.