title: Endotoxin depletes ascorbate in the guinea pig heart. Protective effects of vitamins C and E against oxidative stress.
abstract: The effect of acute endotoxin-induced septic shock on myocardium oxidative stress after low or high vitamin C and/or E dietary supplementation was studied in guinea pigs, laboratory animals which, like human, do not have capacity for ascorbate synthesis. Neither the antioxidant enzymes or GSH were modified by endotoxin and vitamin treatments. Vitamin E showed a strong capacity to protect the myocardium against both enzymatic and non-enzymatic lipid peroxidation even in the presence of endotoxin. Vitamin C supplementation increased heart ascorbate whereas endotoxic shock totally depleted the heart ascorbate of vitamin C supplemented animals without changing vitamin E. Endotoxin significantly increased myocardium uric acid, a marker of ischemia induced oxidative stress, in animals fed with low vitamin C levels. This increase was totally prevented in vitamin C supplemented, but not in vitamin E supplemented animals. Strongly depressed levels of plasma vitamin C have been recently described in sepsis in human patients. The results suggest that ascorbate is a primary antioxidant target in the heart of endotoxin treated mammals lacking the capacity to synthesize ascorbate and that ascorbate can have a protective value against endotoxin-induced free radical damage in the myocardium. Implications of these results for the possible preventive role of vitamin C in humans during sepsis are discussed.
authors: Department of Animal Biology-II (Animal Physiology), Faculty of Biology Complutense University, Madrid, Spain.
authors: C
authors: C
authors: Rojas
authors: S
authors: S
authors: Cadenas
authors: A
authors: A
authors: Herrero
authors: J
authors: J
authors: Méndez
authors: G
authors: G
authors: Barja
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D002374:Catalase / Q000378:metabolism; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D018805:Sepsis / Q000517:prevention & control; D014527:Uric Acid / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D004731:Endotoxins; D008070:Lipopolysaccharides; D014810:Vitamin E; D014527:Uric Acid; D002374:Catalase; D005979:Glutathione Peroxidase; D005978:Glutathione; D001205:Ascorbic Acid