Antioxidants attenuate endotoxin-gentamicin induced acute renal failure in rats.
The synergistic mechanism by which endotoxin enhances the nephrotoxic potential of gentamicin is unknown. In this study, we attempted to shed light on this mechanism by injecting rats with endotoxin plus gentamicin. Renal injury was assessed by measuring creatinine, inulin and PAH clearance, NADH levels and electrolyte reabsorption, for 24 hr following this injection. Gentamicin alone (20 mg/100 g) induced no renal injury, while endotoxin without gentamicin (0.075 mg/100 g) induced mild injury. However, endotoxin plus gentamicin resulted in acute renal failure. In an attempt to halt the progressive renal dysfunction, the antioxidants NAO (5 mg/100 g), Vitamin E (0.2 mg/100 g per day) and dimethylthiourea (DMTU-50 mg/100 g) were administered, or early endotoxin tolerance was induced before injecting the rats with endotoxin plus gentamicin. The reduction in renal function was markedly slower in rats administered with antioxidants compared with untreated rats. Similar results were obtained with endotoxin tolerance. These data suggest that NAO, vitamin E, DMTU and endotoxin tolerance are potentially beneficial in arresting progressive renal damage associated with endotoxin plus gentamicin.
Zurovsky
Y
Y
Department of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
Haber
C
C
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000633:toxicity*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005839:Gentamicins / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D007677:Kidney Function Tests; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D004731:Endotoxins; D016166:Free Radical Scavengers; D005839:Gentamicins; D010936:Plant Extracts; D014810:Vitamin E; C038983:1,3-dimethylthiourea; D013890:Thiourea