{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:35:48Z","timestamp":1760574948054,"version":"build-2065373602"},"reference-count":19,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,1,11]],"date-time":"2006-01-11T00:00:00Z","timestamp":1136937600000},"content-version":"vor","delay-in-days":6129,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[1989,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The effects of cimetidine (CIM) (an inhibitor of the hepatic microsomal monooxygenase system) on the metabolism and hepatotoxicity of trichloroethylene (TRI) were studied in male Sprague\u2010Dawley rats. Rats were given three doses of 120 mg\/kg i.p. (low\u2010dose regimen) of CIM at 0, 6 and 11 h for 1 day, or ten doses of 200 mg\/kg (high\u2010dose regimen) at 8, 11, 14 and 17 h for 2 days and 8 and 11 h on 3rd day. Trichloroethylene (0.5 or 0.65 ml\/kg) was administered i.p. 1 h after 2nd dose (low\u2010dose regimen) or 9th dose (high\u2010dose regimen) of CIM. In the low\u2010dose regimen study, the activity of hepatic microsomal aminopyrine <jats:italic>N<\/jats:italic>\u2010demethylase was decreased 1 and 5 h after the second dose and 7 h after the third dose of CIM, but became normal 20 h after the last dose. The cytochrome P\u2010450 content and the activities of aniline hydroxylase and epoxide hydratase remained unchanged. Trichloroethylene at both dose levels produced liver toxicity, as verified by increase in activities of SDH and SGPT as well as by liver histology. Cimetidine alone had no such effect. An apparent reduction in TRI toxicity by CIM (at both dose regimens) could be observed histologically. The biochemical tests (SDH and SGPT) corroborated the histological changes only when TRI was given at a dose of 0.5 ml\/kg combined with a high\u2010dose regimen of CIM. Cimetidine at both dose regimens had a tendency to decrease the <jats:italic>in vivo<\/jats:italic> metabolism of TRI. These results therefore indicate that CIM may have a short\u2010lived inhibitory effect on the hepatic mixed\u2010function oxidase system, resulting in some protective effect on TRI hepatotoxicity.<\/jats:p>","DOI":"10.1002\/jat.2550090202","type":"journal-article","created":{"date-parts":[[2006,10,14]],"date-time":"2006-10-14T12:08:28Z","timestamp":1160827708000},"page":"75-81","source":"Crossref","is-referenced-by-count":0,"title":["Effect of cimetidine on hepatic biochemical changes, liver toxicity and major urinary metabolite excretion of trichloroethylene in rats"],"prefix":"10.1002","volume":"9","author":[{"given":"Helene","family":"Landriault","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard","family":"Sirois","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saroj","family":"Chakrabarti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel G.","family":"Cote","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,1,11]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-198207010-00002"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1080\/15287397709529469"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-73-5-713"},{"key":"e_1_2_1_5_2","first-page":"637","article-title":"Enhancement of the hepatotoxicity of trichloroethylene by inducers of drug metabolism","volume":"7","author":"Carlson G. 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