TY - JOUR
T1 - Protective effects of apocynin against cisplatin-induced oxidative stress and nephrotoxicity
AU - Chirino, Yolanda I.
AU - Sánchez-González, Dolores Javier
AU - Martínez-Martínez, Claudia Maria
AU - Cruz, Cristino
AU - Pedraza-Chaverri, José
N1 - Funding Information:
This work was supported by UNAM DGAPA IN207007. Axiovert 200 M confocal microscope was donated by Fundación Gonzalo Rio Arronte IAP Mexico. We appreciate the collaboration in grammar and style checking of Edna Jiménez Torres.
PY - 2008/3/12
Y1 - 2008/3/12
N2 - Cis-diamminedichloroplatinum (II) (cisplatin) is an effective chemotherapeutic agent successfully used in the treatment of a wide range of tumors; however, nephrotoxicity has restricted its clinical use. Several studies have shown that reactive oxygen species are involved in cisplatin-induced nephrotoxicity, including hydrogen peroxide, hydroxyl radical and superoxide anion (O2{radical dot}-). The source of O2{radical dot}- in cisplatin-induced renal damage has not been established. The aim of this study was to investigate if NADPH oxidase is involved in cisplatin-induced nephrotoxicity using apocynin, a widely used NADPH oxidase inhibitor. Rats were studied 3 days after a single injection of cisplatin (7.5 mg/kg, i.p.). Apocynin was given in the drinking water (2 g/L) 7 days before and 3 days after cisplatin injection. Apocynin treatment was able to ameliorate the renal histological damage and the increase in blood urea nitrogen, serum creatinine, and urinary excretion of total protein, N-acetyl-β-d-glucosaminidase and glutathione-S-transferase induced by cisplatin. In addition, the protective effect of apocynin was associated with the amelioration of cisplatin-induced oxidative and nitrosative stress. Our data suggest that O2{radical dot}- derived from NADPH oxidase triggers some of the side effects due to cisplatin administration.
AB - Cis-diamminedichloroplatinum (II) (cisplatin) is an effective chemotherapeutic agent successfully used in the treatment of a wide range of tumors; however, nephrotoxicity has restricted its clinical use. Several studies have shown that reactive oxygen species are involved in cisplatin-induced nephrotoxicity, including hydrogen peroxide, hydroxyl radical and superoxide anion (O2{radical dot}-). The source of O2{radical dot}- in cisplatin-induced renal damage has not been established. The aim of this study was to investigate if NADPH oxidase is involved in cisplatin-induced nephrotoxicity using apocynin, a widely used NADPH oxidase inhibitor. Rats were studied 3 days after a single injection of cisplatin (7.5 mg/kg, i.p.). Apocynin was given in the drinking water (2 g/L) 7 days before and 3 days after cisplatin injection. Apocynin treatment was able to ameliorate the renal histological damage and the increase in blood urea nitrogen, serum creatinine, and urinary excretion of total protein, N-acetyl-β-d-glucosaminidase and glutathione-S-transferase induced by cisplatin. In addition, the protective effect of apocynin was associated with the amelioration of cisplatin-induced oxidative and nitrosative stress. Our data suggest that O2{radical dot}- derived from NADPH oxidase triggers some of the side effects due to cisplatin administration.
KW - Apocynin
KW - Cisplatin
KW - NADPH oxidase
KW - Nephrotoxicity
KW - Superoxide anion (O{radical dot})
UR - http://www.scopus.com/inward/record.url?scp=39549122554&partnerID=8YFLogxK
U2 - 10.1016/j.tox.2007.12.007
DO - 10.1016/j.tox.2007.12.007
M3 - Artículo
C2 - 18243469
SN - 0300-483X
VL - 245
SP - 18
EP - 23
JO - Toxicology
JF - Toxicology
IS - 1-2
ER -