期刊论文详细信息
The Japanese Journal of Pharmacology
Acetaminophen-Derived Activation of Liver Microsomal Glutathione S-Transferase of Rats
Hisaharu Nakanishi1  Takahiro Yokomakura2  Tatsumi Nagamine3  Masato Yonamime2  Yoko Aniya2  Tomoyuki Koyama2 
[1] Tropical Technology Center Limited;Laboratory of Physrology and Pharmacology, School of Health Saences;Clinical Laboratory of the University Hospital, Faculty of Medicine, University of the Ryukyus
关键词: Acetaminophen;    Microsome;    Glutathione S-transferase;    Glutathione peroxidase;    Enzyme activation;   
DOI  :  10.1254/jjp.72.175
学科分类:药理学
来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society
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【 摘 要 】

References(32)Cited-By(16)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. Cyiosolic 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.

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