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Trolox protects rat hepatocytes against oxyradical damage and the ischemic rat liver from reperfusion injury.

Abstract
Trolox, a hydrophilic analog of vitamin E, was reported to scavenge peroxyl radicals from artificial systems better than its parent compound. Here we examined the possible cytoprotective effect of Trolox in cultured hepatocytes and in the rat liver. In cultured rat hepatocytes, 0.5 to 16 mmol/L Trolox (with optimum between 1 to 2 mmol/L) was observed to prolong the survival of cells exposed to oxyradicals generated with xanthine oxidase-hypoxanthine. The protection by 1 mmol/L Trolox surpassed that provided by either ascorbate, mannitol, superoxide dismutase and/or catalase--each at a level giving its maximal protection in the same system. In both a global and partial model of hepatic ischemia-reperfusion in rats, infusion of Trolox (7.5 to 10 mumol/kg body weight) just before reflow reduced by greater than 80% the liver necrosis sustained in untreated (no Trolox) control rats. Such organ salvage was apparently accompanied by approximately 50% reduction in the amount of hepatic conjugated dienes, which were quantified by a highly specific radiochemical assay. Since conjugated dienes are presumed to be good "markers" of oxyradical damage, our data may have provided a semiquantitative link between free radical-induced necrosis and its chemical imprint in vivo. The data also indicated a relatively rapid and potent antioxidant-like action by Trolox on rat hepatocytes and on the postischemic reperfused rat liver.
AuthorsT W Wu, N Hashimoto, J X Au, J Wu, D A Mickle, D Carey
JournalHepatology (Baltimore, Md.) (Hepatology) Vol. 13 Issue 3 Pg. 575-80 (Mar 1991) ISSN: 0270-9139 [Print] United States
PMID1999327 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Chromans
  • Free Radicals
  • Hypoxanthines
  • Hypoxanthine
  • Xanthine Oxidase
  • 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid
Topics
  • Animals
  • Cells, Cultured
  • Chromans (therapeutic use)
  • Free Radicals
  • Hypoxanthine
  • Hypoxanthines (pharmacology)
  • Ischemia (drug therapy)
  • Liver (blood supply, cytology, drug effects)
  • Liver Diseases (drug therapy, metabolism)
  • Male
  • Rats
  • Rats, Inbred Strains
  • Reperfusion Injury (drug therapy, metabolism)
  • Xanthine Oxidase (pharmacology)

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