Aminoguanidine, a Selective Nitric Oxide Synthase Inhibitor, Attenuates Cyclophosphamide-Induced Renal Damage by Inhibiting Protein Nitration and Poly(ADP-Ribose) Polymerase Activation

BACKGROUND: Cyclophosphamide (CP) is an antineoplastic agent that is used for the treatment of many neoplastic diseases. Renal damage is one of the dose-limiting side effects of CP. Recent studies show that nitrosative stress plays an important role in CP-induced renal damage. AIM: The purpose of our study was to investigate whether aminoguanidine (AG), a selective inducible nitric oxide synthase inhibitor, protects against CP-induced nitrosative stress and renal damage. METHOD: Renal damage was induced in 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 h before administration of CP. The control rats received AG or saline alone. All the rats were killed 16 h after the administration of CP or saline. Pretreatment with AG prevented CP-induced nitration of protein tyrosine and poly(ADP-ribose) polymerase (PARP) activation. RESULT: Pretreatment with AG attenuated CP-induced renal damage. The present study demonstrates that AG is effective in preventing CP-induced renal damage and also that the protective effect is from its ability to inhibit nitric oxide-induced protein nitration and PARP activation. CONCLUSION: The present study shows that AG can prevent CP-induced renal damage by inhibiting protein tyrosine nitration and PARP activation. Thus, a more efficient and comfortable therapy can be achieved for patients in need of CP treatment. AG appears to be a promising drug for the prevention of nephrotoxicity of CP.