Title: Methimazole protection of rats against gentamicin-induced nephrotoxicity.

Authors: Elfarra, A A; Duescher, R J; Sausen, P J; O'Hara, T M; Cooley, A J

Published In Can J Physiol Pharmacol, (1994 Oct)

Abstract: 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.

PubMed ID: 7882190

MeSH Terms: Animals; Blood Urea Nitrogen; Gentamicins/analysis; Gentamicins/antagonists & inhibitors*; Gentamicins/toxicity; In Vitro Techniques; Kidney Cortex/chemistry; Kidney Cortex/drug effects*; Kidney Cortex/pathology; Kidney Diseases/chemically induced*; Kidney Diseases/pathology; Male; Methimazole/pharmacology*; Rats; Sulfhydryl Compounds/analysis