Toxic Dose of a Simple Phenolic Antioxidant, Protocatechuic Acid, Attenuates the Glutathione Level in ICR Mouse Liver and Kidney

Abstract

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.

Thiol modification by bioactivated polyphenols and its potential role in skin inflammation

“…14) In addition, the toxic effects of BHT, possibly through CYP, led us to the idea that much attention should be paid to the administered dose of monophenols not only in the skin, but also in the liver and kidney, which have significant CYP activities and the potential target tissues for toxic effects of PCA and some tyrosinase substrates. 15,16) In the present study, we have indicated that the catechol-type polyphenols can modify sulfhydryl groups in a phenol oxidase-dependent manner. The possible involvement of polyphenol bioactivation in the enhancement of TPA-induced skin inflammation was also suggested.…”

Ameliorative Effects of Caffeic Acid on Lead Accumulation and Oxidative Stress in Lead-Exposed Mice

“…On the other hand, protocatechuic acid at concentrations above 2.5 mM showed in vitro pro-oxidation activity linked to the decrease in reduced glutathione and increase in cellular TBARS [33]. Nakamura et al [34] described hepatotoxic and nephrotoxic effect of protocatechuic in mice at doses of 500 mg/kg, linked to decrease in GSH. The prooxidation effect of CA on Cu2 + -induced LDL oxidation has been also described at its high concentrations [35].…”

In vitroeffects of rosmarinic acid on glutathione reductase and glucose 6-phosphate dehydrogenase

“…However, RA inhibits amylase activity, the extent of amylase inhibition correlated with increased concentration of RA (McCue & Shetty, 2004) Similarly, in a concentration-dependent manner, aldose reductase, phospholipase A(2) from different sources, and carboxypeptidase A are inhibited with RA (Kusano et al, 1998;da Silva et al, 2009;Koukoulitsa et al, 2010). Overdoses of protocatechuic acid, which is a phenolic antioxidant, can disturb the detoxification of other electrophilic toxicants (Nakamura et al, 2001).…”