Trolox and ascorbate: are they synergistic in protecting liver cells in vitro and in vivo?
From in vitro studies involving multilamellar liposomes or other artificial systems, several groups of workers have deduced that Trolox (a water-soluble analogue of vitamin E) and ascorbate are synergistic antioxidants. Here, we demonstrate that while Trolox and ascorbate individually protect cultured hepatocytes against oxyradicals generated either with xanthine oxidase plus hypoxanthine or with hydrogen peroxide, the two antioxidants do not appear to be synergistic when used in equimolar combinations. Also, in a rat model of hepatic ischemia-reperfusion, we observed that infusion of Trolox or ascorbate (7.5-10 mumol/kg body weight) into the postischemic liver reduced the reperfusion injury by 76 or 67%, respectively. However, when both compounds were used together (each at the same dose as used separately), the organ salvage amounted to only 79%. Therefore, there is no evidence of synergism between Trolox and ascorbate in our in vitro and especially in vivo systems.
Zeng
L H
LH
Department of Clinical Biochemistry, University of Toronto, Ont., Canada.
Wu
J
J
Carey
D
D
Wu
T W
TW
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D004357:Drug Synergism; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000633:toxicity; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000633:toxicity; D007511:Ischemia; D008099:Liver / Q000098:blood supply / Q000166:cytology / Q000187:drug effects*; D008297:Male; D009336:Necrosis; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000517:prevention & control; D014969:Xanthine Oxidase / Q000633:toxicity
D000975:Antioxidants; D002839:Chromans; D005609:Free Radicals; D007042:Hypoxanthines; D019271:Hypoxanthine; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase; D001205:Ascorbic Acid; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid