{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T10:53:11Z","timestamp":1761216791609},"reference-count":0,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,10,4]],"date-time":"2004-10-04T00:00:00Z","timestamp":1096848000000},"content-version":"vor","delay-in-days":1556,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology &amp; Toxicology"],"published-print":{"date-parts":[[2000,7]]},"abstract":"<jats:title>Abstract:<\/jats:title><jats:p>Female ICR mice were treated with cocaine either alone or in combination with one of several cytochrome P450 (CYP) inducers, i.e. phenobarbital, \u03b2\u2010ionone, dexamethasone and \u03b2\u2010naphthoflavone. Cocaine\u2010induced hepatotoxicity was first observed by pretreatment with phenobarbital, \u03b2\u2010ionone or dexamethasone in accordance with significant elevation of cocaine N\u2010demethylation, the first step of cocaine bioactivation. The hepatic lesions occured in the periportal region (zone 1) by phenobarbital and \u03b2\u2010ionone and in the perivenular region (zone 3) by dexamethasone. The activities of the enzyme specific for CYP isozyme were determined to elucidate the effects of pretreatment with CYP inducers. \u03b2\u2010Naphthoflavone induced CYP1A and 2B but had no effects on hepatotoxicity by cocaine. On the other hand, \u03b2\u2010ionone enhanced hepatotoxicity without induction of CYP3A. Activities of cocaine N\u2010demethylase correlated well with CYP2A (r=0.83) and CYP2B (r=0.81). Cocaine N\u2010demethylation was inhibited particularly by addition of the CYP2A specific inhibitor, 8\u2010methoxypsoralen. Moreover, pretreatment with 8\u2010methoxypsoralen produced a marked inhibition of the hepatotoxicity induced by cocaine in phenobarbital\u2010treated mice. These results suggest that cocaine\u2010induced hepatotoxicity in female mice was mediated in part by CYP2A, participating in cocaine N\u2010demethylation.<\/jats:p>","DOI":"10.1111\/j.0901-9928.2000.870105.x","type":"journal-article","created":{"date-parts":[[2004,10,4]],"date-time":"2004-10-04T15:56:05Z","timestamp":1096905365000},"page":"26-32","source":"Crossref","is-referenced-by-count":18,"title":["Participation of CYP2A in Cocaine\u2010Induced Hepatotoxicity in Female Mice"],"prefix":"10.1111","volume":"87","author":[{"given":"Kimiko","family":"Aoki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masafumi","family":"Takimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidekazu","family":"Ota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takemi","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,10,4]]},"container-title":["Pharmacology &amp; Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.0901-9928.2000.870105.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.0901-9928.2000.870105.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,29]],"date-time":"2023-10-29T14:04:26Z","timestamp":1698588266000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.0901-9928.2000.870105.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,7]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2000,7]]}},"alternative-id":["10.1111\/j.0901-9928.2000.870105.x"],"URL":"https:\/\/doi.org\/10.1111\/j.0901-9928.2000.870105.x","archive":["Portico"],"relation":{},"ISSN":["0901-9928"],"issn-type":[{"value":"0901-9928","type":"print"}],"subject":[],"published":{"date-parts":[[2000,7]]}}}