METHIMAZOLE PROTECTION OF RATS AGAINST GENTAMICIN-INDUCED NEPHROTOXICITY

Methimazole was previously shown to protect rats, mice, and (or) dogs against cisplatin-, cephaloridine-, 2-bromophydroquinone-, and S-(1,2- dichlorovinyl)-L-cysteine-induced nephrotoxicity. In this study, methi mazole effects on gentamicin (GM) induced nephrotoxicity were examined . Rats given GM (40 mg/kg) twice daily for 10 days exhibited higher bl ood urea nitrogen (BUN) concentrations and severe necrosis of virtuall y all proximal tubules compared with saline-treated controls. Rats cot reated with methimazole (20 mg/kg) exhibited minimal proximal tubular necrosis and were protected against GM-induced increase in BUN concent rations, despite having higher kidney GM concentrations. Rats given GM alone for 3 days exhibited no proximal tubular necrosis and no elevat ion of BUN values. However, these rats exhibited an increase in nonpro tein disulfide concentrations and a decrease in renal protein thiol an d protein disulfide concentrations, as opposed to rats given GM and me thimazole. 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 a cting as an antioxidant within the kidneys.