Protective effect of antiinflammatory corticosteroid triamcinolone in cisplatin nephrotoxicity.
The corticosteroid, triamcinolone, was examined as a potential antagonist for the nephrotoxicity of cisplatin in female Wistar rats. The changes in renal function and renal morphology were assessed on the 3rd day after administration of cisplatin (7.5 mg/kg BW) and in animals given triamcinolone retard (4 mg/kg BW) 6 h before administration of cisplatin. Pretreatment with triamcinolone resulted in much less severe changes in renal function after cisplatin administration (serum urea: triamcinolone plus cisplatin 14.29 +/- 1.90 mg/l, cisplatin alone 21.60 +/- 2.34 mg/l, p < 0.05, control 2.78 +/- 0.19 mg/l, serum creatinine: triamcinolone plus cisplatin 0.21 +/- 0.02 mg/l, cisplatin alone 0.30 +/- 0.02 mg/l, p < 0.05, control 0.06 +/- 0.01 mg/l). In contrast to cisplatin-treated animals in triamcinolone-pretreated rats alterations of water content were found neither in renal cortex (triamcinolone plus cisplatin 3.39 +/- 0.16 g/g dry weight, cisplatin alone 4.07 +/- 0.07 g/g dry weight, control 3.07 +/- 0.07 g/g dry weight) nor in outer medulla (triamcinolone plus cisplatin 4.20 +/- 0.22 g/g dry weight, cisplatin alone 4.98 +/- 0.21 g/g dry weight, control 3.84 +/- 0.11 g/g dry weight) compared to control. The structure of the kidney following cisplatin administration demonstrated extensive lesions of S3 segments of the proximal tubule. The changes in proximal convoluted tubules were widespread and ranged from the decrease of the amount of microvilli to loss of brush border or even to cell death. In triamcinolone-pretreated rats the structure of the cortex appeared to be virtually normal and tissue of medulla was only slightly damaged.
Reznik
L V
LV
Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg.
Gambaryan
S P
SP
D000818:Animals; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005260:Female; D007668:Kidney / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014221:Triamcinolone / Q000494:pharmacology*
D014221:Triamcinolone; D002945:Cisplatin