Abstract
The aim of the present work was to investigate a new mechanism likely contributing to the toxic action of acetaminophen especially to explore the possible inhibition of glutathione reductase through an acetaminophen-glutathione conjugate (APAP-SG). APAP-SG conjugate was synthesized by organic synthesis and purified by column chromatography.
The inhibitory effect of the conjugate on two types of glutathione reductase (from yeasts and rat hepatocytes) was tested spectrophotometrically. In addition, the enzyme acitivty (from hepatocytes lysate) was decreased to 79?7%, 67?2% and 39?7%, in 0.37, 1.48 and 3.7 mM concentration of the conjugate, respecitvely.
We ound that glutathione reductase, the essential enzyme of the antioxidant system, was dosedependently inhibited by the product of acetaminophen metabolism - the conjugate of acetaminophen and glutathione.