Yonamine M, Aniya Y, Yokomakura T, Koyama T, Nagamine T, Nakanishi H
Laboratory of Physiology and Pharmacology, School of Health Sciences, University of the Ryukyus, Okinawa, Japan.
Jpn J Pharmacol. 1996 Oct;72(2):175-81. doi: 10.1254/jjp.72.175.
Effect of acetaminophen on glutathione (GSH) S-transferase and related drug metabolizing enzymes was studied in vivo. Rats were given acetaminophen (250 mg/kg, i.p.) 24 hr after the treatment with 3-methylcholanthrene (25 mg/kg, i.p.) and killed by decapitation at indicated times. Liver microsomal GSH S-transferase activity was increased to 331%, 193% and 158% of the control level at 3, 6 and 12 hr, respectively, after the administration of acetaminophen, while GSH content in the liver was markedly decreased at 3 and 6 hr. The increase in the transferase activity was not recovered by the treatment with dithiothreitol. Microsomal GSH peroxidase activity was significantly enhanced at 3 hr. Cytosolic GSH S-transferase and aniline hydroxylase in microsomes were gradually decreased with the increase in the time after administration of acetaminophen. Vmax values of both GSH S-transferase and GSH peroxidase activities in microsomes were increased at 3 hr. Two Km values were obtained for the peroxidase in the control, while only one was observed after the acetaminophen treatment. These results indicate that acetaminophen is converted via cytochrome P-450 to the reactive intermediate N-acetyl-p-benzoquinone imine, which binds to microsomal GSH S-transferase, resulting in the activation of the enzyme.
