Methimazole protection of rats against gentamicin-induced nephrotoxicity.
Methimazole was previously shown to protect rats, mice, and (or) dogs against cisplatin-, cephaloridine-, 2-bromohydro-quinone-, and S-(1,2-dichlorovinyl)-L-cysteine-induced nephrotoxicity. In this study, methimazole effects on gentamicin (GM) induced nephrotoxicity were examined. Rats given GM (40 mg/kg) twice daily for 10 days exhibited higher blood urea nitrogen (BUN) concentrations and severe necrosis of virtually all proximal tubules compared with saline-treated controls. Rats cotreated with methimazole (20 mg/kg) exhibited minimal proximal tubular necrosis and were protected against GM-induced increase in BUN concentrations, despite having higher kidney GM concentrations. Rats given GM alone for 3 days exhibited no proximal tubular necrosis and no elevation of BUN values. However, these rats exhibited an increase in nonprotein disulfide concentrations and a decrease in renal protein thiol and protein disulfide concentrations, as opposed to rats given GM and methimazole. Together the results show that methimazole was an effective antagonist of GM-induced nephrotoxicity. Methimazole did not inhibit GM renal uptake but may protect against GM-induced nephrotoxicity by acting as an antioxidant within the kidneys.
Elfarra
A A
AA
Department of Comparative Biosciences, University of Wisconsin, Madison 53706-1102.
Duescher
R J
RJ
Sausen
P J
PJ
O'Hara
T M
TM
Cooley
A J
AJ
D000818:Animals; D001806:Blood Urea Nitrogen; D005839:Gentamicins / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000633:toxicity; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008713:Methimazole / Q000494:pharmacology*; D051381:Rats; D013438:Sulfhydryl Compounds / Q000032:analysis
D005839:Gentamicins; D013438:Sulfhydryl Compounds; D008713:Methimazole