Propyl gallate as a hepatoprotector in vitro and in vivo

Recently, there has been renewed interest in propyl gallate, a preservative in foods and fuels. This compound, which exhibits antimicrobial activity, has been found to be toxicologically safe after almost 30 years of evaluation. In the present study, we examined whether propyl gallate is a hepatoprotective antioxidant, and investigated some of its bases of action vis-à-vis Trolox, a vitamin E analogue. In isolated rat hepatocytes, propyl gallate prolonged substantially cell survival against oxyradicals generated with xanthine oxidase-hypoxanthine. The protection was dose dependent and excelled that of Trolox, mannitol, or ascorbate, each at or near its optimum level in the same system. In rats undergoing an 80-min partial hepatic ischemia, infusion of propyl gallate at 20 mumol/kg body weight just before a 24-hr reperfusion salvaged the organ by 80.0 +/- 11.5%, an extent comparable to that with Trolox. Mechanistically, we found that propyl gallate (a) protected hepatocytes against the cascade of oxyradicals produced by xanthine oxidase-hypoxanthine; (b) protected hepatocytes against superoxide radicals generated specifically by menadione; (c) protected the functionally important hepatic vascular endothelial cells more effectively than Trolox against xanthine oxidase-hypoxanthine, and (d) approximately halved the amount of lipid conjugated dienes (a more specific marker of oxyradical damage than malondialdehyde) formed in tissues after oxidant damage. Therefore, there are fundamental reasons why propyl gallate is an effective antioxidant-based hepatoprotector, both in vitro and in vivo.