Superoxide anion production and expression of gp91(phox) and p47(phox) are increased in glomeruli and proximal tubules of cisplatin-treated rats.
The chemotherapeutic drug cisplatin has some side effects including nephrotoxicity that has been associated with reactive oxygen species production, particularly superoxide anion. The major source of superoxide anion is nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase. However, the specific segment of the nephron in which superoxide anion is produced has not been identified. Rats were sacrificed 72 h after cisplatin injection (7.5 mg/kg), and kidneys were obtained to isolate glomeruli and proximal and distal tubules. Cisplatin induced superoxide anion production in glomeruli and proximal tubules but not in distal tubules. This enhanced superoxide anion production was prevented by diphenylene iodonium, an inhibitor of NADPH oxidase. Consistently, this effect was associated with the increased expression of gp91(phox) and p47(phox), subunits of NADPH oxidase. The enhanced superoxide anion production in glomeruli and proximal tubules, associated with the increased expression of gp91(phox) and p47(phox), is involved in the oxidative stress in cisplatin-induced nephrotoxicity.
Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), University City, Mexico, D.F., 04510, Mexico.
Joyce
J
Trujillo
Eduardo
E
Molina-Jijón
Omar Noel
ON
Medina-Campos
Rafael
R
Rodríguez-Muñoz
José Luis
JL
Reyes
Diana
D
Barrera
José
J
Pedraza-Chaverri
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism*
D000970:Antineoplastic Agents; D008562:Membrane Glycoproteins; D013481:Superoxides; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D002945:Cisplatin
Cisplatin; NADPH Oxidase; Proximal Tubules; Superoxide Anion