{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T15:26:37Z","timestamp":1778599597238,"version":"3.51.4"},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2013,9,5]],"date-time":"2013-09-05T00:00:00Z","timestamp":1378339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Acetaminophen overdose is the most frequent cause of acute liver injury. The main mechanism of acetaminophen toxicity has been attributed to oxidation of acetaminophen. The oxidation product is very reactive and reacts with glutathione generating acetaminophen\u2013glutathione conjugate (APAP\u2010SG). Although this conjugate has been recognized to be generally nontoxic, we have found recently that APAP\u2010SG could produce a toxic effect. Therefore, the aim of our study was to estimate the toxicity of purified APAP\u2010SG by characterizing the inhibitory effect in human glutathione reductase (GR) and comparing that to the inhibitory effect of the natural inhibitor reduced glutathione. We used two types of human GR: recombinant and freshly purified from red blood cells. Our results show that GR was significantly inhibited in the presence of both APAP\u2010SG and reduced glutathione. For example, the enzyme activity of recombinant and purified GR was reduced in the presence of 4\u2009m<jats:sc>m<\/jats:sc> APAP\u2010SG (with 0.5\u2009m<jats:sc>m<\/jats:sc> glutathione disulfide) by 28% and 22%, respectively. The type of enzyme inhibition was observed to be competitive in the cases of both APAP\u2010SG and glutathione. As glutathione inhibits GR activity in cells under physiological conditions, the rate of enzyme inhibition ought to be weaker in the case of glutathione depletion that is typical of acetaminophen overdose. Notably, however, enzyme activity likely remains inhibited due to the presence of APAP\u2010SG, which might enhance the pro\u2010oxidative status in the cell. We conclude that our finding could reflect some other pathological mechanism that may contribute to the toxicity of acetaminophen. Copyright \u00a9 2013 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.2914","type":"journal-article","created":{"date-parts":[[2013,9,5]],"date-time":"2013-09-05T03:07:03Z","timestamp":1378350423000},"page":"968-973","source":"Crossref","is-referenced-by-count":15,"title":["Comparison of inhibitory effects between acetaminophen\u2013glutathione conjugate and reduced glutathione in human glutathione reductase"],"prefix":"10.1002","volume":"34","author":[{"given":"Erika","family":"N\u00fddlov\u00e1","sequence":"first","affiliation":[{"name":"Department of Biological and Biochemical Sciences Faculty of Chemical Technology University of Pardubice  Pardubice Czech Republic"},{"name":"Department of Analytical Chemistry Faculty of Chemical Technology University of Pardubice  Pardubice Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Vrbov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Biological and Biochemical Sciences Faculty of Chemical Technology University of Pardubice  Pardubice Czech Republic"},{"name":"Department of Analytical Chemistry Faculty of Chemical Technology University of Pardubice  Pardubice Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petr","family":"\u010cesla","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry Faculty of Chemical Technology University of Pardubice  Pardubice Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbora","family":"Jankovi\u010dov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Biological and Biochemical Sciences Faculty of Chemical Technology University of Pardubice  Pardubice Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karel","family":"Ventura","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry Faculty of Chemical Technology University of Pardubice  Pardubice Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom\u00e1\u0161","family":"Rou\u0161ar","sequence":"additional","affiliation":[{"name":"Department of Biological and Biochemical Sciences Faculty of Chemical Technology University of Pardubice  Pardubice Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,9,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pep.2011.08.031"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi9926431"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1995.472_b.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/20014091111677"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)41206-4"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(91)90163-D"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.220176997"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2009.07.001"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfi336"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2011.01.025"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1989.tb14500.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20293"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.13.10.1169"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2008.05.005"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx700029u"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(76)80508-X"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.52.070183.003431"},{"key":"e_1_2_7_20_1","first-page":"77","article-title":"Assessment of glutathione reductase inhibition","volume":"17","author":"Nydlova E","year":"2011","journal-title":"Sci. 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