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 pmolkg body weight) just before reflow reduced by > 80% the liver necrosis sustained in untreated (no Trolox) control rats. Such organ salvage was apparently accompanied by -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 uiuo. The data also indicated a relatively rapid and potent antioxidant-like action by Trolox on rat hepatocytes and on the postischemic reperfused rat liver. (HEPATOLOGY 1991;13:575-580.) Trolox ( Trolox C ; 6-hydroxy-2,5,7,8-te trame thylchroman-2-carboxylic acid) is a water-soluble analog of vitamin E or a-tocopherol. Trolox had been reported to be an effective preservative in animal fats and vegetable oils (1) and an excellent antioxidant in uitro (2-3). In SDS micelles, Trolox was shown to scavenge peroxyl radicals eight times better than a-tocopherol (4). In 1985, Casini, Pompella and Comporti (5) reported that injecting Trolox along with propylene glycol intraperitoneally into rats reduced the liver damage caused by bromobenzene, iodobenzene and dimethylmaleate poisoning. Recently,