ROLE OF GLUTATHIONE FOR CISPLATIN NEPHROTOXICITY IN YOUNG AND ADULT-RATS

被引：31

作者：

APPENROTH, D

WINNEFELD, K

机构：

[1] Institute of Pharmacology, Toxicology Friedrich Schiller University, D-O-6900, Jena

[2] Research Laboratory of the Surgical Clinic Friedrich Schiller University, D-O-6900, Jena

来源：

RENAL FAILURE | 1993年 / 15卷 / 02期

关键词：

Ac-cys; BSO; Cisplatin; Developing rats; GSH; Nephrotoxicity;

D O I：

10.3109/08860229309046144

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Investigations were done in 10- and 55-day-old Wistar rats. Glutathione (GSH) level in kidney was decreased by 8 mmol buthionine sulfoximine (BSO)/100 g BW There was no effect on the renal function and nephrotoxicity of cisplatin (0.6 mg CP/100 g BW) in adult rats. In young rats BSO treatment was followed by nephrotoxic effects. Pt concentration remained unaffected by BSO in young and adult rats. GSH concentration in kidney was increased by 100 mg acetyl-cysteine (ac-cys)/100 g BW. CP nephrotoxicity was lower in young as well as in adult ac-cys-treated rats. Pt levels in renal tissue were significantly decreased in rats from both age groups. From our results we conclude that the beneficial effect of high GSH concentration in renal tissue on CP nephrotoxicity is the result of decreased Pt concentration in kidney.

引用

页码：135 / 139

页数：5

共 28 条

[1] Levi J., Jacos C., Kalman S.M., McTigue M., Weiner M.W., Mechanism of cis-platinum nephrotoxicity: 1. Effects of sulfhydryl groups in rat kidneys, J Pharmacol Exp Ther, 213, pp. 545-550, (1980)
[2] Long D.P., Repta A.J., Cisplatin: Chemistry, distribution and biotransformation, Biopharm Drug Dispos, 2, pp. 1-16, (1981)
[3] Ross D., Glutathione, free radicals and chemotherapeutic agents, Pharm Ther, 37, pp. 231-249, (1980)
[4] Reed D.J., Glutathione: Toxicological implications, Ann Rev Pharmacol Toxicol, 30, pp. 603-631, (1980)
[5] Suzuki C.A.M., Cherian M.G., The interaction of cis-diammine-dichloroplatinum with metallothionein and glutathione in rat liver and kidney, Toxicology, 64, pp. 113-127, (1990)
[6] Nakano S., Gemba M., Potentiation of cisplatin-induced lipid per-oxidation in kidney cortical slices by glutathione depletion, Japan J Pharmacol, 50, pp. 87-92, (1989)
[7] Zuzino F., Pratesi G., Micheloni A., Cavaletti E., Sala F., Tofanetti O., Protective effect of reduced glutathione against cisplatin-induced renal and systemic toxicity and its influence on the therapeutic activity of the antitumour drug, Chem-Biol Interact, 70, pp. 89-95, (1989)
[8] Leyland-Jones B., Morrow C., Tate S., Urmacher C., Gordon C., Young C.W., Cis-Diaminedichloro-platinum(II) nephrotoxicity and its relationship to renal y-glutamyl transpeptidase and glutathione, Cancer Res, 43, (1983)
[9] Litterst C.L., Tong S., Hirokata Y., Siddik Z.H., Alteration in hepatic and renal levels of glutathione and activities of glutathione s-transferases from rats treated with cis-dichlorodiammine-platinum-II, Cancer Chemother Pharmacol, 8, pp. 67-71, (1982)
[10] Maines M.D., Differential effect of cis-platinum on regulation of liver and kidney heam and heamoprotein metabolism, Biochem J, 237, pp. 713-718, (1986)

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