Antioxidants attenuate endotoxin-induced acute renal failure in rats.
Acute kidney dysfunction, manifested by a reduction in renal blood flow and in the glomerular filtration rate, is a common finding in septic shock. The pathogenetic mechanisms responsible for the renal dysfunction observed in the endotoxemic murine model are not completely understood. In this study, an attempt was made to halt the progressive renal dysfunction in the rats by administration of the antioxidants dimethylthiourea (DMTU) (50 mg/100 g) and superoxide dismutase (SOD) (0.4 mg/100 g) before endotoxin infusion (0.5 mg/100 g), or by inducing endotoxin tolerance. Renal function, assessed by creatinine, inulin, and p-aminohippuric acid clearance, nicotinamide adenine dinucleotide, and electrolyte reabsorption, was measured 4 hours after the endotoxin infusion. Renal function declined in all rats throughout the study period. However, the reduction in renal function was markedly slower in endotoxemic rats administered DMTU and SOD compared with untreated rats. Similar results were found following induction of endotoxin tolerance. These data suggest that DMTU, SOD, and endotoxin tolerance may be potentially beneficial in halting progressive renal damage associated with endotoxemia.
Zurovsky
Y
Y
Department of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Gispaan
I
I
D058186:Acute Kidney Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000502:physiology; D006090:Gram-Negative Bacteria; D007677:Kidney Function Tests; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D008297:Male; D009243:NAD / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D000975:Antioxidants; D004731:Endotoxins; D008070:Lipopolysaccharides; D009243:NAD; C038983:1,3-dimethylthiourea; D013482:Superoxide Dismutase; D013890:Thiourea