{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T01:39:27Z","timestamp":1759541967771},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2006,6,9]],"date-time":"2006-06-09T00:00:00Z","timestamp":1149811200000},"content-version":"vor","delay-in-days":3904,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Biochem. Toxicol."],"published-print":{"date-parts":[[1995,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Repletion of depleted cellular reduced glutathione (GSH) levels in oxidative stress and exposure to arylating agents is a strategy for the development of antidotes to chemical toxicity. The effect of GSH, reduced glutathione ethyl monoester (GSHEt), and reduced glutathione ethyl diester (GSHEt<jats:sub>2<\/jats:sub>) on the cytotoxicity of hydrogen peroxide, 1\u2010chloro\u20102,4\u2010dinitrobenzene (CDNB), and menadione to P388D<jats:sub>1<\/jats:sub> macrophages in vitro was investigated. The median toxic concentration TC<jats:sub>50<\/jats:sub> values of the toxicants were hydrogen peroxide 24 \u00b1 2 mM (<jats:italic>N<\/jats:italic> = 19), CDNB 63 \u00b1 6 \u03bcM (<jats:italic>N<\/jats:italic> = 18), and menadione 30 \u00b1 4 \u03bcM (<jats:italic>N<\/jats:italic> = 22). Reduced glutathione, GSHEt, and GSHEt<jats:sub>2<\/jats:sub> were poor antidotes to hydrogen peroxide toxicity. Indeed, the observed antidote effects were attributed to the nonenzymatic reaction of the GSH derivatives with hydrogen peroxide in the extracellular medium. Reduced glutathione ethyl diester was a more potent antidote of CDNB\u2010 and menadione\u2010mediated toxicity than GSHEt and GSH. For cell incubations with the approximate median toxic concentration TC<jats:sub>50<\/jats:sub> values of hydrogen peroxide, CDNB, and menadione, the respective median effective antidote concentration EC<jats:sub>50<\/jats:sub> values were GSHEt 23.8 \u00b1 4.1 mM (<jats:italic>N<\/jats:italic> = 9), 3.6 \u00b1 0.6 mM (<jats:italic>N<\/jats:italic> = 11), and 226 \u00b1 93 \u03bcM (<jats:italic>N<\/jats:italic> = 12); and GSHEt<jats:sub>2<\/jats:sub> 20.4 \u00b1 1.9 mM (<jats:italic>N<\/jats:italic> = 6), 603 \u00b1 2 \u03bcM (<jats:italic>N<\/jats:italic> = 9), and 7.6 \u00b1 2.3 \u03bcM (<jats:italic>N<\/jats:italic> = 12). Reduced glutathione ethyl diester was a potent antidote to CDNB\u2010 and menadione\u2010induced toxicities but not to hydrogen peroxide\u2010induced toxicity under acute intoxication conditions. \u00a9 1996 John Wiley &amp; Sons, Inc.<\/jats:p>","DOI":"10.1002\/jbt.2570100504","type":"journal-article","created":{"date-parts":[[2006,10,18]],"date-time":"2006-10-18T02:00:31Z","timestamp":1161136831000},"page":"245-250","source":"Crossref","is-referenced-by-count":8,"title":["Reduced glutathione esters\u2014antidotes to toxicity. Cytotoxicity induced by hydrogen peroxide, 1\u2010chloro\u20102,4\u2010dinitrobenzene, and menadione in murine P388D<sub>1<\/sub> macrophages in vitro"],"prefix":"10.1002","volume":"10","author":[{"given":"Harjit S.","family":"Minhas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J.","family":"Thornalley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,6,9]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1979.59.3.527"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840050529"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.3109\/00498258609038976"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(90)90045-4"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1993.tb18025.x"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)77815-6"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(91)90296-A"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(93)90301-C"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.2.936"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.141.3.394"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(85)90723-4"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2750535"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.19.9171"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(94)00518-Q"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112126"},{"key":"e_1_2_1_17_2","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1016\/S0021-9258(19)41830-9","article-title":"Regulation of \u03b3\u2010glutamylcysteine synthetase by non\u2010allosteric feedback inhibition by glutathione","volume":"250","author":"Richman P. 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