Peroxynitrite decomposition catalyst ameliorates renal damage and protein nitration in cisplatin-induced nephrotoxicity in rats.
BACKGROUND
Oxidative stress is involved in cisplatin-nephrotoxicity. However, it has not completely established if reactive nitrogen species and nitrosative stress are involved in this experimental model. The purpose of this work was to study the role of peroxynitrite, a reactive nitrogen specie, in cisplatin-nephrotoxicity using the compound 5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato iron (III) (FeTPPS), a soluble complex able to metabolize peroxynitrite.


RESULTS
In rats treated with cisplatin (a single intraperitoneal dose of 7.5 mg/kg body weight), renal nitrosative stress was made evident by the increase in 3-nitrotyrosine on day 3. In addition, cisplatin-induced nephrotoxicity was evident by the histological damage of proximal tubular cells and by the increase in (a) serum creatinine, (b) blood urea nitrogen, and (c) urinary excretion of N-acetyl-beta-D-glucosaminidase and total protein. Cisplatin-induced nitrosative stress and nephrotoxicity were attenuated by FeTPPS-treatment (15 mg/kg body weight, intraperitoneally, every 12 hours for 3 days).


CONCLUSIONS
Nitrosative stress is involved in cisplatin-induced nephrotoxicity in rats. Our data suggest that peroxynitrite is involved, at least in part, in cisplatin-induced nephrotoxicity and protein nitration.
Departamento de Biología, Facultad de Química, Edificio B, Segundo Piso, Lab 209, Ciudad Universitaria, UNAM, México D.F. México. irasema_chirino@hotmail.com
Yolanda I
YI
Chirino
Rogelio
R
Hernández-Pando
José
J
Pedraza-Chaverrí
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002384:Catalysis; D002945:Cisplatin / Q000633:toxicity*; D005920:Glomerular Mesangium / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008297:Male; D008665:Metalloporphyrins / Q000737:chemistry / Q000627:therapeutic use*; D030421:Peroxynitrous Acid / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014556:Urine
C466420:5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron(III) chloride; D008665:Metalloporphyrins; D026361:Reactive Nitrogen Species; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D002945:Cisplatin