{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T20:37:17Z","timestamp":1777667837862,"version":"3.51.4"},"reference-count":30,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2001,8,1]],"date-time":"2001-08-01T00:00:00Z","timestamp":996624000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hum Exp Toxicol"],"published-print":{"date-parts":[[2001,8]]},"abstract":"<jats:p>\n                    In this study, we have carried out an investigation to determine if chlorzoxazone (CZX) is a suitable probe drug for predicting hepatic injury in carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    )-intoxicated rats. The animals received oral doses of CCl\n                    <jats:sub>4<\/jats:sub>\n                    (0.25, 0.5 and 1 ml\/kg) 24 h prior to intraperitoneal administration of CZX. The total CYP and CYP2E1 content, as well as the aniline and CZX hydroxylase activity (V max and CL\n                    <jats:sub>int<\/jats:sub>\n                    ), was reduced depending on the dose of CCl\n                    <jats:sub>4<\/jats:sub>\n                    administered. At the highest concentration (128 mM) of diethyldithiocarba mate, a specific inhibitor of CYP2E1, the production of 6-hydroxychlorzoxazone (HCZX) in microsomes from CCl\n                    <jats:sub>4<\/jats:sub>\n                    treated rats was reduced by about 85%. The IC\n                    <jats:sub>50<\/jats:sub>\n                    value in microsomes from CCl\n                    <jats:sub>4<\/jats:sub>\n                    treated rats was between 3 and 5 M. The production of HCZX and the activity of aniline hydroxylase in CCl\n                    <jats:sub>4<\/jats:sub>\n                    treated rats correlated with the amount of rat CYP2E1 protein (r =0.881, P &lt;0.001 and r =0.822, P &lt;0.001, respectively). The elimination of CZX by CCl\n                    <jats:sub>4<\/jats:sub>\n                    treated rats was reduced and the HCXZ production in the CCl\n                    <jats:sub>4<\/jats:sub>\n                    treated group was less than that in the olive oil-treated control group. The correlations between the intrinsic clearance (CL\n                    <jats:sub>int<\/jats:sub>\n                    :V max \/Km) in vitro and the total body clearance (CL\n                    <jats:sub>tot<\/jats:sub>\n                    ) of CZX hydroxylation and the elimination half-life (t\n                    <jats:sub>1\/2<\/jats:sub>\n                    ) of CZX in vivo in CCl\n                    <jats:sub>4<\/jats:sub>\n                    treated rats were high (r =0.839, P &lt;0.001 and r = 0.828, P &lt;0.001, respectively). In addition, the metabolic plasma HCZX\/CZX ratio did not require multiple blood sampling and, 2 h after CZX administration in vivo, there was also a high correlation with the CL\n                    <jats:sub>int<\/jats:sub>\n                    (V max \/ K m) in vitro (r = 0.909, P&lt;0.01). In conclusion, these results from this study demonstrate that CZX is a good probe for monitoring the inhibition of metabolism in rats due to CCl\n                    <jats:sub>4<\/jats:sub>\n                    treatment.\n                  <\/jats:p>","DOI":"10.1191\/096032701682692937","type":"journal-article","created":{"date-parts":[[2003,4,3]],"date-time":"2003-04-03T19:38:43Z","timestamp":1049398723000},"page":"381-385","source":"Crossref","is-referenced-by-count":6,"title":["Chlorzoxazone: a probe drug the metabolism of which can be used to monitor                 one-point blood sampling in the carbon tetrachloride intoxicated rat"],"prefix":"10.1177","volume":"20","author":[{"given":"E","family":"Tanaka","sequence":"first","affiliation":[{"name":"Institute of Community Medicine, University of Tsukuba, Tsukuba-shi,                         Ibaraki-ken 305-8575, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2001,8,1]]},"reference":[{"key":"atypb1","doi-asserted-by":"publisher","DOI":"10.1021\/tx00018a012"},{"key":"atypb2","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-199502000-00007"},{"key":"atypb3","doi-asserted-by":"publisher","DOI":"10.1159\/000139381"},{"key":"atypb4","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(94)90524-X"},{"key":"atypb5","first-page":"1429","volume":"25","author":"Raucy JL","year":"1997","journal-title":"Drug Metab Dispos"},{"key":"atypb6","first-page":"1009","volume":"727","author":"Dilger K","year":"1979","journal-title":"J Hepatol"},{"key":"atypb7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.1998.00612.x"},{"key":"atypb8","doi-asserted-by":"publisher","DOI":"10.3109\/00498259109039506"},{"key":"atypb9","doi-asserted-by":"publisher","DOI":"10.3109\/00498259209053116"},{"key":"atypb10","doi-asserted-by":"publisher","DOI":"10.3109\/00498259509061911"},{"key":"atypb11","doi-asserted-by":"publisher","DOI":"10.1007\/s002040050666"},{"key":"atypb12","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a128453"},{"key":"atypb13","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)82245-5"},{"key":"atypb14","doi-asserted-by":"publisher","DOI":"10.1038\/227680a0"},{"key":"atypb15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.76.9.4350"},{"key":"atypb16","doi-asserted-by":"publisher","DOI":"10.1007\/s002040050403"},{"key":"atypb17","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"atypb18","doi-asserted-by":"publisher","DOI":"10.1016\/0300-483X(95)03216-3"},{"key":"atypb19","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2710.2000.00282.x"},{"key":"atypb20","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.6.2.1537462"},{"key":"atypb21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1996.tb01764.x"},{"key":"atypb22","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-8206.1998.tb00985.x"},{"key":"atypb23","doi-asserted-by":"publisher","DOI":"10.1021\/tx00036a015"},{"key":"atypb24","first-page":"438","volume":"23","author":"Yamazaki H","year":"1995","journal-title":"Drug Metab Dispos"},{"key":"atypb25","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-199504000-00003"},{"key":"atypb26","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-199506000-00002"},{"key":"atypb27","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-199606000-00002"},{"key":"atypb28","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)49601-4"},{"key":"atypb29","doi-asserted-by":"publisher","DOI":"10.1080\/004982598238886"},{"key":"atypb30","doi-asserted-by":"publisher","DOI":"10.1016\/0009-9236(95)90227-9"}],"container-title":["Human &amp; Experimental Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1191\/096032701682692937","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1191\/096032701682692937","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:48:05Z","timestamp":1777448885000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1191\/096032701682692937"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,8]]},"references-count":30,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2001,8]]}},"alternative-id":["10.1191\/096032701682692937"],"URL":"https:\/\/doi.org\/10.1191\/096032701682692937","relation":{},"ISSN":["0960-3271","1477-0903"],"issn-type":[{"value":"0960-3271","type":"print"},{"value":"1477-0903","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,8]]}}}