![[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}
|
|
|
|
|
||
J Levi, C Jacobs, SM Kalman, M McTigue and MW Weiner
cis-Diamminedichloroplatinum (CP), an important chemotherapeutic agent, produces acute renal failure by an unknown mechanism. Other heavy metals, such as mercury, are thought to be nephrotoxic by reacting with sulfhydryl (SH) groups. To investigate the mechanism of CP nephrotoxicity, F344 rats were injected once with 6 mg of CP per kg. After 96 hr, the blood urea nitrogen rose to 140 mg/100 ml. The SH concentration in control kidneys was 20.4 +/- 0.1 muml/g wet weight. Total renal SH groups decreased to a maximum of 14% at 120 hr (P less than .01). The fall in SH groups was entirely due to a decrease of protein-bound SH groups. Cell fractionation studies showed that the greatest decline of SH groups occurred in the "mitochondrial" and "cytosol" fractions. These fractions also had the highest Pt concentrations. There was no stoichiometric relationship between Pt accumulation and the change in SH groups. Furthermore, in vitro studies demonstrated that CP does not directly interact with SH groups. To determine if the change in renal SH groups was nonspecific effect of acute injury, renal failure was induced with glycerol (5 g/kg i.m.). Total SH groups per kidney increased after glycerol. These results indicate that the decrease in renal SH groups produced by CP is not due to nonspecific tubular necrosis. The present findings suggest the possibility that the nephrotoxic effects of CP may be related to depletion of SH groups. However, a direct cause-effect relationship has not been established.
This article has been cited by other articles:
|
|
 |
|
  D. Sheikh-Hamad Cisplatin-induced cytoxicity: is the nucleus relevant? Am J Physiol Renal Physiol, July 1, 2008; 295(1): F42 - F43. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Fatima, A. N. K. Yusufi, and R. Mahmood Effect of cisplatin on renal brush border membrane enzymes and phosphate transport Human and Experimental Toxicology, December 1, 2004; 23(12): 547 - 554. [Abstract] [PDF]
|
|
|
|
|
|
G. Nowak, P. M. Price, and R. G. Schnellmann Lack of a functional p21WAF1/CIP1 gene accelerates caspase-independent apoptosis induced by cisplatin in renal cells Am J Physiol Renal Physiol, September 1, 2003; 285(3): F440 - F450. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Nowak Protein Kinase C-alpha and ERK1/2 Mediate Mitochondrial Dysfunction, Decreases in Active Na+ Transport, and Cisplatin-induced Apoptosis in Renal Cells J. Biol. Chem., November 1, 2002; 277(45): 43377 - 43388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A A Abdel-Gayoum, K B El-Jenjan, and K A Ghwarsha Hyperlipidaemia in cisplatin-induced nephrotic rats Human and Experimental Toxicology, July 1, 1999; 18(7): 454 - 459. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Potdevin, F. Courjault-Gautier, B. M. Du Sorbier, P. Ripoche, and H. J. Toutain Role of Protein Thiols in Inhibition of Sodium-Coupled Glucose Uptake by Cisplatin in Renal Brush-Border Membrane Vesicles J. Pharmacol. Exp. Ther., January 1, 1998; 284(1): 142 - 150. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
