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Hypoxia decreased theophylline metabolic clearance (Cl<jats:sub>M<\/jats:sub>) from 1.73\u00b10.43 to 1.48\u00b10.13\u2003ml\u2003min<jats:sup>\u22121<\/jats:sup>\u2003kg<jats:sup>\u22121<\/jats:sup> (<jats:italic>P<\/jats:italic>&lt;0.05), and reduced (<jats:italic>P<\/jats:italic>&lt;0.05) the formation clearance of theophylline metabolites, 3\u2010methylxanthine (3MX), 1\u2010methyluric acid (1MU) and 1,3\u2010dimethyluric acid (1,3DMU). Hypoxia reduced the amount of CYP1A1 and 1A2 but increased CYP3A6 proteins.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Turpentine\u2010induced inflammatory reaction reduced (<jats:italic>P<\/jats:italic>&lt;0.05) the formation clearance of 3MX, 1MU, and 1,3DMU, and diminished the amount of CYP1A1, 1A2 and 3A6 proteins. However, when combined with hypoxia, inflammation partially prevented the decrease in Cl<jats:sub>M<\/jats:sub>, especially by impeding the reduction of 1,3DMU. The amount of CYP1A1 and 1A2 remained reduced but the amount of CYP3A6 protein returned to normal values.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Pre\u2010treatment with 3MC augmented the Cl<jats:sub>M<\/jats:sub> by 114% (<jats:italic>P<\/jats:italic>&lt;0.05) due to the increase in the formation clearance of 3MX, 1MU and 1,3DMU. 3MC treatment increased the amount of CYP1A1 and 1A2 proteins. Pre\u2010treatment with 3MC prevented the hypoxia\u2010induced decrease in amount and activity of the P450.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>It is concluded that acute moderate hypoxia and an inflammatory reaction individually reduce the amount and activity of selected apoproteins of the P450. However, the combination of hypoxia and the inflammatory reaction restores P450 activity to near normal values. On the other hand, pre\u2010treatment with 3MC prevents the hypoxia\u2010induced depression of the P450.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>128<\/jats:bold>, 365\u2013373; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702795\">10.1038\/sj.bjp.0702795<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702795","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:11:06Z","timestamp":1106943066000},"page":"365-373","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Effect of hypoxia alone or combined with inflammation and 3\u2010methylcholanthrene on hepatic cytochrome P450 in conscious rabbits"],"prefix":"10.1111","volume":"128","author":[{"given":"J","family":"Kurdi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Maurice","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A O S","family":"El\u2010Kadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Ong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Dalkara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P M","family":"B\u00e9langer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Du Souich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1139\/o70-133"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"3985","DOI":"10.1016\/S0021-9258(17)41731-5","article-title":"Down\u2010regulation of P4501A1 and P4501A2 mRNA expression in isolated hepatocytes by oxidative stress","volume":"269","author":"BARKER C.W.","year":"1994","journal-title":"J. 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