Toxic dose of a simple phenolic antioxidant, protocatechuic acid, attenuates the glutathione level in ICR mouse liver and kidney

It has previously been reported that a toxic dose of protocatechuic acid (PA), a naturally occurring simple phenolic antioxidant in dietary plant foodstuff, has a potential to enhance tumorigenesis and induce contact hypersensitivity in mouse skin. In this study, the modifying effect of a toxic dose of PA on the glutathione (GSH) level in mouse liver and kidney was examined. Intraperitoneal administration of PA (500 mg/kg) caused significant hepatic and nephrotic GSH depletion. Interestingly, slight but significant hepatotoxicity and nephrotoxicity, characterized by the enhancement of plasmic alanine aminotrasferase (ALT) activity and urea level, respectively, were also observed. The subchronic administration of PA (0.1% in drinking water) for 60 days showed not only a significant decrease in the GSH level in kidney but also a significant enhancement of ALT activity in plasma. The protective role of GSH for acute hepatotoxicity using GSH-depleted mice administered a GSH synthesis inhibitor buthionine sulfoximine was also demonstrated. Thus, it is suggested that overdoses of PA can disturb the detoxification of other electrophilic toxicants including ultimate carcinogens.