Effect of high dietary cholesterol on gentamicin-induced nephrotoxicity in rabbits

Abstract.

Administration of gentamicin to rabbits intramuscularly at a dose of 80 mg/kg per day for 5 days induced nephrotoxicity exhibited by significantly (P<0.001) elevated serum urea and creatinine levels and a significant (P<0.001) decrease in renal cortical alkaline phosphatase (ALP) activity, in addition to tubular necrosis revealed by the histopathological examination of the kidney cortices. The deranged parameters returned to normal within 1 week of drug withdrawal, except the cortical ALP activity, which was still significantly lower compared to control. In contrast, feeding of 2% cholesterol-supplemented diet (CSD) to the rabbits for 15 days did not produce any nephrotoxic effects. However, the concurrent feeding of CSD for 15 days and gentamicin treatment at a dose of 80 mg/kg per day for 5 days, starting from day 10 of feeding, resulted in extensive nephrotoxic effects which were more severe than those observed with the gentamicin alone, with delayed recovery of the injured kidney following drug withdrawal. Gentamicin treatment produced significant elevation in serum total cholesterol, which was greater in animals fed with CSD. The serum triglyceride levels in the groups injected with gentamicin were also significantly greater than their respective controls. However, the serum phosphlipids were significantly reduced with gentamicin treatment and this reduction was greater in animals fed with cholesterol and treated with the drug. The liver cholesterol contents in animals fed with the CSD were significantly higher than those fed with the plain diet. However, the kidney cortices of the animals injected with the gentamicin showed significantly increased total phospholipid contents compared to their respective controls. On the other hand, the liver function was not altered in any of the experimental groups. In summary, the present results suggest that cholesterol feeding exacerbated the gentamicin-induced nephrotoxicity. Moreover, it delayed the period required by the injured kidney to recover back to normal. However, neither gentamicin treatment nor cholesterol feeding, or both together, had any injurious effects on the liver.