Role of zinc in the abatement of hepatocellular damage and mortality incidence in endotoxemic rats.
Intraperitoneal administration of zinc (ZnIP) as zinc chloride prior to or simultaneously with a lethal quantity of intraperitoneally administered Salmonella typhimurium endotoxin significantly protected rats against toxin-induced mortality and hepatocellular damage. Pretreatment with amounts of zinc chloride ranging from 0.4 to 2.0 mg/100 g of body weight resulted in 80 to 100% survival compared with 10% survival in untreated control rats at 24 h after endotoxin treatment. Zinc chloride treatment in excess of 2.0 mg/100 g of body weight appeared to be toxic and provided diminished protection. In contrast with the protection obtained with ZnIP, intravenously administered zinc did not provide protection. The effectiveness of ZnIP to enhance survival if it was given after endotoxin was greatly diminished as a function of time after endotoxin. The extent of hepatocellular damage was assessed at various times after endotoxin administration in ZnIP-treated and untreated rats by measurement of plasma ornithine carbamoyltransferase activity and histological examination of liver sections. Endotoxin absorption from the peritoneal cavity and hepatic uptake were studied by using 51Cr-labeled endotoxin. ZnIP pretreatment significantly reduced 51Cr-labeled endotoxin content of blood and liver when compared to untreated controls, and effectively prevented endotoxin-induced elevations in plasma ornithine carbamoyltransferase activity and hepatic tissue necrosis. These data indicate that protection afforded by ZnIP treatment results as a consequence of the ability of zinc to diminish absorption of the toxin from the peritoneal cavity and subsequent hepatic uptake.
D000042:Absorption; D000818:Animals; D004731:Endotoxins; D008099:Liver / Q000187:drug effects; D008107:Liver Diseases / Q000517:prevention & control; D008297:Male; D009336:Necrosis; D009954:Ornithine Carbamoyltransferase / Q000097:blood; D051381:Rats; D012486:Salmonella typhimurium / Q000276:immunology; D014115:Toxemia / Q000188:drug therapy*; D015032:Zinc / Q000627:therapeutic use*
D004731:Endotoxins; D009954:Ornithine Carbamoyltransferase; D015032:Zinc