PROPYL GALLATE AS A HEPATOPROTECTOR IN-VITRO AND IN-VIVO

Recently, there has been renewed interest in propyl gallate, a preserv ative in foods and fuels. This compound, which exhibits antimicrobial activity, has been found to be toxicologically safe after almost 30 ye ars of evaluation. In the present study, we examined whether propyl ga llate is a hepatoprotective antioxidant, and investigated some of its bases of action vis-a-vis Trolox, a vitamin E analogue. In isolated ra t hepatocytes, propyl gallate prolonged substantially cell survival ag ainst oxyradicals generated with xanthine oxidase-hypoxanthine. The pr otection was dose dependent and excelled that of Trolox, mannitol, or ascorbate, each at or near its optimum level in the same system. In ra ts undergoing an 80-min partial hepatic ischemia, infusion of propyl g allate at 20 mu mol/kg body weight just before a 24-hr reperfusion sal vaged the organ by 80.0 +/- 11.5%, an extent comparable to that with T rolox. Mechanistically, we found that propyl gallate (a) protected hep atocytes against the cascade of oxyradicals produced by xanthine oxida se-hypoxanthine; (b) protected hepatocytes against superoxide radicals generated specifically by menadione; (c) protected the functionally i mportant hepatic vascular endothelial cells more effectively than Trol ox against xanthine oxidase-hypoxanthine, and (d) approximately halved the amount of lipid conjugated dienes (a more specific marker of oxyr adical damage than malondialdehyde) formed in tissues after oxidant da mage. Therefore, there are fundamental reasons why propyl gallate is a n effective antioxidant-based hepatoprotector, both in vitro and in vi vo.