Endotoxin increases hepatic susceptibility to lipid peroxidation: a possible role of iron.
The purpose of this study was to investigate the possible mechanism by which endotoxin enhances peroxidative damage to membrane lipids. Male B6C3 mice were treated with endotoxin intraperitoneally 0 or 20 mg/kg body weight for 24 h. Freshly prepared liver homogenate was incubated with either 1-5 mM of reduced glutathione (GSH), glucose, H(2)O(2), ascorbic acid (AA), FeSO(4), FeCl(3), EDTA, FeCl(3) plus AA, AA plus EDTA or EDTA plus FeCl(3) in phosphate-buffered saline (PBS), pH 7.0, or PBS, at 37 degrees C for 60 min. The levels of lipid peroxidation products, thiobarbituric acid reactants (TBAR), were significantly higher in the liver of endotoxin-treated mice, and the values were markedly increased following incubation. Compared to PBS, incubation with H(2)O(2), FeCl(3), FeSO(4), and AA, but not glucose, significantly enhanced TBAR formation. The greatest increase of TBAR was found when AA and FeCl(3) were added together. On the other hand, EDTA and GSH inhibited the formation of TBAR during incubation. When added before AA, EDTA completely inhibited the peroxidative effect of AA or FeSO4, and when added subsequent to AA, EDTA partially prevented the adverse effect of AA. The results obtained suggest that ionic iron plays an important role in initiating endotoxin-induced peroxidative damage to membrane lipids, and that AA may be involved in releasing iron from its protein complex and/or maintaining ionic iron in a reduced or catalytic state.
Graduate Center for Nutritional Sciences and Kentucky Agricultural Experiment Station, University of Kentucky, Lexington, KY 40506-0054, USA.
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Ibrahim
U-S
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Lee
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Chow
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004336:Drug Antagonism; D004492:Edetic Acid / Q000494:pharmacology; D004731:Endotoxins / Q000008:administration & dosage / Q000633:toxicity*; D005947:Glucose / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007501:Iron / Q000008:administration & dosage / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000737:chemistry
D002614:Chelating Agents; D004731:Endotoxins; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D004492:Edetic Acid; D006861:Hydrogen Peroxide; D007501:Iron; D005978:Glutathione; D005947:Glucose; D001205:Ascorbic Acid