Increased renal susceptibility to gentamicin in the rat with obstructive jaundice. Role of lipid peroxidation.
To study whether renal susceptibility to nephrotoxic stimuli is increased in obstructive jaundice, the effect of gentamicin on the renal function in bile duct-ligated rats was investigated. Gentamicin (50 mg/kg/day, subcutaneously) or saline was given to bile duct-ligated rats or sham-operated rats for six days. Mortality in the bile duct-ligated group that received gentamicin was 64% whereas that in the other groups was 0%. In the bile duct-ligated group, although serum creatinine and blood urea nitrogen were minimally affected, focal granulo-vacuolar degeneration in the proximal tubule was observed, which was accompanied by an increase in renal malondialdehyde. Gentamicin significantly increased serum creatinine and blood urea nitrogen levels and caused marked degeneration in the proximal tubule in the bile duct-ligated group, which was accompanied by a further increase in renal malondialdehyde, while these changes were not observed in the sham group. The kidney in obstructive jaundice appears to be susceptible to gentamicin. Enhanced production of oxygen radicals may be responsible for this effect.
Tajiri
K
K
Second Department of Internal Medicine, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
Miyakawa
H
H
Marumo
F
F
Sato
C
C
D000818:Animals; D001806:Blood Urea Nitrogen; D001651:Cholestasis, Extrahepatic / Q000209:etiology / Q000503:physiopathology*; D003135:Common Bile Duct / Q000601:surgery; D003404:Creatinine / Q000097:blood; D005839:Gentamicins / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008026:Ligation; D015227:Lipid Peroxidation / Q000502:physiology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D005839:Gentamicins; D008315:Malondialdehyde; D003404:Creatinine