Protective effect of aminoguanidine against cyclophosphamide-induced oxidative stress and renal damage in rats

Background: Cyclophosphamide (CP) is widely used in the treatment of tumors and B-cell malignant disease, such as lymphoma, myeloma, chronic lymphocytic leukemia, and Waldenstrom's macroglobulinemia. Renal damage is one of the dose-limiting side effects of CP. Oxidative stress is reported to play important roles in CP-induced renal damage.

Aim: To find out whether aminoguanidine (AG) protects against CP-induced oxidative stress and renal damage.

Method: Renal damage was induced in the rats by administration of a single injection of CP at a dose of 150 mg/kg body weight intraperitoneally. For the AG pretreatment studies, the rats were injected intraperitoneally with AG at a dose of 200 mg/kg body weight 1 hour before administration of CP. The control rats received AG or saline alone. All the rats were killed 16 hours after the administration of CP or saline. The kidneys were used for histological examination by LIGHT microscopy and biochemical assays--malondialdehyde, protein carbonyl content, reduced glutathione (GSH), and the activities of antioxidant enzymes including Glutathione Peroxidase (GPx), glutathione S transferase (GSTase), catalase, glutathione reductase, and myeloperoxidase (MPO), a marker of neutrophil infiltration.

Results: Pretreatment with AG attenuated CP-induced renal damage histologically. Pretreatment with AG prevented CP-induced lipid peroxidation, protein oxidation, depletion of reduced GSH, and loss of activities of the antioxidant enzymes including GPx, catalase, and GSTase and also MPO activity.

Conclusion: The results of the present study reveal that AG can prevent CP-induced renal damage by inhibiting oxidative stress. Thus, AG may be useful for prevention of the nephrotoxicity of CP.