Modulation of Cyclophosphamide-Induced Cellular Toxicity by Diphenylmethyl Selenocyanate In Vivo, an Enzymatic Study

Abstract

AIM: Cyclophosphamide (CP) is one of the most widely used alkylating antineoplastic agents that damage normal cells while killing cancerous cells in vivo. The use of CP in treating cancer patients is limited due to its severe toxicities induced mainly by oxidative stress. Diphenylmethyl selenocyanate is a synthetic organoselenium compound shown to act as a potent antioxidant in chemically induced murine toxicity and carcinogenesis models in vivo. In the present study, this compound has been evaluated for its protective potential against CP-induced toxicity in Swiss albino mice. METHODS: CP was administered intraperitoneally (50 mg/kg) and diphenylmethyl selenocyanate was given orally (3 mg/kg) in a pretreatment and concomitant treatment schedule, and the effects were assessed by estimating lipid peroxidation level, phase II detoxifying enzyme system, blood hemoglobin level, serum transaminase activity, and nitrite content. RESULTS: Diphenylmethyl selenocyanate significantly (P＜0.05) increased glutathione-S-transferase, glutathione peroxidase, and catalase levels whereas decreased the lipid peroxidation levels in both liver and lung tissues of the animals given CP. Superoxide dismutase was increased significantly in liver (P＜0.05) but not in the lung. The selenium compound also significantly (P＜0.05) increased the blood hemoglobin level whereas decreased the transaminase activity in serum and the nitrite content in peritoneal macrophages. CONCLUSION: Our result suggests that diphenylmethyl selenocyanate has the potential to prevent CP-induced cellular toxicity.