![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL
Division of Nephrology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan (M.S., N.K., S.F., H.H., T.T., T.N., T.S.); Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan (M.S., H.M.)
Accumulating evidence suggests that enhanced peroxidative damage caused by reactive oxygen species (ROS) may contribute to the pathogenesis of cisplatin-induced acute renal failure. Nevertheless, little is known about the involvement of oxygen radicals in cisplatin nephropathy. In this study, we investigated the effects of a novel free radical scavenger, 3-methyl-1-phenyl-pyrazolin-5-one (MCI-186; edarabone), on murine proximal tubular cell (PTC) damage induced by exposure to cisplatin in vitro and on renal function in an in vivo model of cisplatin-induced acute renal failure. Edarabone inhibited cisplatin-induced (40 µM, 24 h) cytotoxicity in a concentration-dependent manner (10-5 to 10-3 M). Edarabone also attenuated cisplatin-induced mitochondrial transmembrane potential loss and ROS production of PTCs. In the in vivo study, male Wistar rats were cotreated with cisplatin (5 mg/kg, i.p.) and edarabone (1 or 5 mg/kg, i.v.). Effects of edarabone on the kidney were examined 5 days after treatment. Cisplatin resulted in renal dysfunction, renal tubular damage, mitochondrial damage (assayed by histochemical staining for respiratory chain complex IV), renal protein oxidation (examined by Western blot analysis using a specific antibody for carbonyl group-containing proteins), and tubular apoptosis (determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining). The above changes were attenuated by edarabone treatment. Thus, edarabone exhibited cytoprotective effects in PTCs and renoprotective effects against cisplatin. Our findings suggest that ROS, in particular hydroxyl radicals, are involved in cisplatin nephropathy and that edarabone may be potentially useful in protecting the kidneys and prevention of acute renal failure.
Address correspondence to: Dr. Minoru Satoh, Division of Nephrology, Department of Internal Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan. E-mail: satoh-minoru{at}mx1.tiki.ne.jp
This article has been cited by other articles:
|
|
 |
|
  T. Arai, M. Nonogawa, K. Makino, N. Endo, H. Mori, T. Miyoshi, K. Yamashita, M. Sasada, M. Kakuyama, and K. Fukuda The Radical Scavenger Edaravone (3-Methyl-1-phenyl-2-pyrazolin-5-one) Reacts with a Pterin Derivative and Produces a Cytotoxic Substance That Induces Intracellular Reactive Oxygen Species Generation and Cell Death J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 529 - 538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Prewett, D. S. Deevi, R. Bassi, F. Fan, L. M. Ellis, D. J. Hicklin, and J. R. Tonra Tumors Established with Cell Lines Selected for Oxaliplatin Resistance Respond to Oxaliplatin if Combined with Cetuximab Clin. Cancer Res., December 15, 2007; 13(24): 7432 - 7440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Omori, Y. Shikata, K. Sarai, N. Watanabe, J. Wada, N. Goda, N. Kataoka, K. Shikata, and H. Makino Edaravone mimics sphingosine-1-phosphate-induced endothelial barrier enhancement in human microvascular endothelial cells Am J Physiol Cell Physiol, November 1, 2007; 293(5): C1523 - C1531. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Razzaque Cisplatin nephropathy: is cytotoxicity avoidable? Nephrol. Dial. Transplant., August 1, 2007; 22(8): 2112 - 2116. [Full Text] [PDF]
|
|
|
|
 |
|
 C. Yang, V. Kaushal, S. V. Shah, and G. P. Kaushal Mcl-1 is downregulated in cisplatin-induced apoptosis, and proteasome inhibitors restore Mcl-1 and promote survival in renal tubular epithelial cells Am J Physiol Renal Physiol, June 1, 2007; 292(6): F1710 - F1717. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Choi, Y. J. Piao, M. J. Lim, J. H. Kim, J. Ha, W. Choe, and S. S. Kim Overexpressed Cyclophilin A in Cancer Cells Renders Resistance to Hypoxia- and Cisplatin-Induced Cell Death Cancer Res., April 15, 2007; 67(8): 3654 - 3662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Haruna, N. Kashihara, M. Satoh, N. Tomita, T. Namikoshi, T. Sasaki, T. Fujimori, P. Xie, and Y. S. Kanwar Amelioration of progressive renal injury by genetic manipulation of Klotho gene PNAS, February 13, 2007; 104(7): 2331 - 2336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Kroemer, L. Galluzzi, and C. Brenner Mitochondrial Membrane Permeabilization in Cell Death Physiol Rev, January 1, 2007; 87(1): 99 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zhuang, Y. Yan, R. A. Daubert, J. Han, and R. G. Schnellmann ERK promotes hydrogen peroxide-induced apoptosis through caspase-3 activation and inhibition of Akt in renal epithelial cells Am J Physiol Renal Physiol, January 1, 2007; 292(1): F440 - F447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Seth, C. Yang, V. Kaushal, S. V. Shah, and G. P. Kaushal p53-dependent Caspase-2 Activation in Mitochondrial Release of Apoptosis-inducing Factor and Its Role in Renal Tubular Epithelial Cell Injury J. Biol. Chem., September 2, 2005; 280(35): 31230 - 31239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Sunami, H. Sugiyama, D.-H. Wang, M. Kobayashi, Y. Maeshima, Y. Yamasaki, N. Masuoka, N. Ogawa, S. Kira, and H. Makino Acatalasemia sensitizes renal tubular epithelial cells to apoptosis and exacerbates renal fibrosis after unilateral ureteral obstruction Am J Physiol Renal Physiol, June 1, 2004; 286(6): F1030 - F1038. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
