Renal effects of gentamicin in chronic bile duct ligated rats

Patients with advanced cirrhosis and rats with short-term bile duct ligation (BDL) are prone to develop nephrotoxicity from aminoglycosides. In this study, we characterized the renal response to gentamicin in rats with chronic BDL. BDL and sham-operated (SO) rats were given gentamicin (20 and 40 mg/kg/d) for 7 consecutive days, starting on the 18th postoperative day. Administration of gentamicin to SO group caused a decrease in cortical and medullary prostaglandin E(2)(PGE(2)) generation. However, mild reduction in creatinine clearance and an increase in fractional excretion of sodium occurred only in the BDL rats given the high gentamicin dose. This was accompanied by a reduction in cortical and medullary PGE(2) generation and a reduction in plasma nitric oxide production. In conclusion, gentamicin administration to rats with chronic BDL causes impairment of renal function. This happens only after the occurrence of simultaneous multiple insults to the renal protective mechanisms.