Glutathione Reductase Is Inhibited by Acetaminophen-glutathione Conjugate In Vitro
ČlánekOtevřený přístuppeer-reviewedpostprintDatum publikování
2010
Vedoucí práce
Oponent
Název časopisu
Název svazku
Vydavatel
Elsevier
Abstrakt
Acetaminophen is one of commonly used analgesics and antipyretics. It is a safe drug at therapeutic doses but in the overdose, it causes liver injury which may lead to acute liver failure. The aim of the present work was to investigate a new mechanism contributing to the toxic acting of acetaminophen especially to explore the possible inhibition of glutathione reductase through an acetaminophen-glutathion conjugate. The acetaminophen-glutathione
conjugate was synthesized by the reaction between glutathione and N-acetyl p-benzoquinone imine and purified by column chromatography. The inhibition effect of the conjugate on two types of glutathione reductase (from yeasts and rat hepatocytes) was tested spectrophotometrically. We synthesized the conjugate and found that the enzyme activity was reduced significantly after treatment with different concentrations of acetaminophenglutathione
conjugate in both yeast and hepatocyte glutathione reductases (0.014 U/ml); the
enzyme activity (from hepatocytes) was decreased to 79±7 %, 67±2 % and 39±7 %, in 0.37, 1.48 and 3.7 mM concentration of the conjugate, respectively. We found that glutathione reductase was dose-dependently inhibited by the conjugate of acetaminophen and glutathione. Our finding results in new consequences in description of acetaminophen
toxicity and, in addition, explains previously published findings which have not been fully explainable till now.
Rozsah stran
p. 225-232
ISSN
0862-8408
Trvalý odkaz na tento záznam
Projekt
Zdrojový dokument
Physiological Research. 2010, vol. 59, issue 2
Vydavatelská verze
http://proquest.umi.com/pqdlink?Ver=1&Exp=10-25-2015&FMT=7&DID=2069242961&RQT=309&cfc=1
Přístup k e-verzi
open access
Název akce
ISBN
Studijní obor
Studijní program
Signatura tištěné verze
Umístění tištěné verze
Přístup k tištěné verzi
Klíčová slova
acetaminophen toxicity, glutathione reductase, glutathione, hepatotoxicity