title: Aminoguanidine, a selective nitric oxide synthase inhibitor, attenuates cyclophosphamide-induced renal damage by inhibiting protein nitration and poly(ADP-Ribose) polymerase activation.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Biochemistry, Christian Medical College, Vellore, India. premilaabraham @ yahoo.com
authors: Premila
authors: P
authors: Abraham
authors: Suganthy
authors: S
authors: Rabi
mesh_terms: D000818:Animals; D003520:Cyclophosphamide / Q000009:adverse effects*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009566:Nitrates / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D009566:Nitrates; C002744:3-nitrotyrosine; D014443:Tyrosine; D003520:Cyclophosphamide; D052247:Nitric Oxide Synthase Type II; D011065:Poly(ADP-ribose) Polymerases; C004479:pimagedine