Effect of methimazole and fish oil treatment on gentamicin nephrotoxicity in rats

Gentamicin, a nephrotoxic aminoglycoside antibiotic, was injected into adult male albino rats, alone or together with methimazole and fish oil. The effects on renal and liver functions and renal thiol status were studied. Gentamicin was administered as two i.p. injections (40 mg/kg body weight) for 3, 7 and 10 consecutive days. The animals were sacrificed 12 hours after the last injection. In gentamicin-treated rats, for 7 and 10 days, blood urea nitrogen (BUN) and serum creatinine concentrations and urinary N-acetyl-beta-D-glucosaminidase (NAG) activity were significantly increased compared with saline-treated controls. Administration of methimazole (20 mg/kg) and fish oil (5 ml/kg) together with gentamicin partially protected against the nephrotoxicity induced by gentamicin by returning the urea and creatinine concentrations and urinary NAG activity to normal levels, despite having higher kidney gentamicin concentrations, especially with methimazole. Rats given gentamicin alone for 3 days exhibited no elevation of BNU, serum creatinine and urinary NAG 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 gentamicin and methimazole and rats given gentamicin and fish oil. These results show that methimazole and fish oil were effective antagonists of gentamicin-induced nephrotoxicity. Methimazole did not inhibit gentamicin renal uptake but may protect against gentamicin-induced nephrotoxicity by acting as an antioxidant within the kidneys. On the other hand, fish oil may protect against gentamicin-induced nephrotoxicity by counteracting the biochemical alterations induced by the drug in the renal cortex. We conclude that methimazole and fish oil may be compounds for reducing gentamicin-toxic side effects, including nephrotoxicity, without compromising its antibiotic activity.