{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T05:15:11Z","timestamp":1648530911063},"reference-count":0,"publisher":"Canadian Science Publishing","issue":"3","license":[{"start":{"date-parts":[[1991,3,1]],"date-time":"1991-03-01T00:00:00Z","timestamp":667785600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[1991,3,1]]},"abstract":"<jats:p> To test further the competence of the cirrhotic liver to metabolize xenobiotics, hepatocytes were isolated from control and CCl<jats:sub>4<\/jats:sub>-induced cirrhotic male or female rats. Histologically micronodular cirrhosis was present in all CCl<jats:sub>4<\/jats:sub>-treated rats, while control rats had normal livers. Portal perfusion pressure and intrahepatic collagen content were also significantly increased by CCl<jats:sub>4<\/jats:sub> administration. In male rats, no significant differences in levels of circulating transaminases nor in alkaline phosphatase was observed between cirrhotic and control rats, while CCl<jats:sub>4<\/jats:sub>-treated females had slightly higher than normal serum transaminase levels at the time of the studies. Hepatocytic cytochrome P-450 and basal xenobiotic biotransformation were unaffected by micronodular cirrhosis in both genders; calculation of the aminopyrine and 7-ethoxycoumarin intrinsic clearances (Cl<jats:sub>i<\/jats:sub>) revealed, however, a slightly decreased transformation potential in hepatocytes obtained from cirrhotic females, a phenomenon not observed in cirrhotic male rats. It is speculated that the observed reduction in Cl<jats:sub>i<\/jats:sub> may have been independent of cirrhosis per se, owing to the perduring cytotoxic effect of CCl<jats:sub>4<\/jats:sub> as evidenced by the higher than normal level of transaminases in female rats. Finally, male rats were subjected to in vivo administration of phenobarbital or 3-methylcholanthrene; both compounds led to significant induction of the mixed-function oxidase system, which was similar in magnitude and in selectivity in control and cirrhotic rats as illustrated by calculation of the Michaelis\u2013Menten kinetic parameters for aniline p-hydroxylation, aminopyrine-N-demethylation, 7-ethoxycoumarin-O-deethylation, and p-nitrophenol UDP-glucuronyl transferase. We conclude mat in well-established but compensated and hepatolysis-free micronodular cirrhosis, hepatocytes are fully able to transform xenobiotics and to respond normally and selectively to inducers of drug metabolism.Key words: micronodular cirrhosis, hepatocytes, drug metabolism, intact hepatocyte hypothesis, phenobarbital, 3-methylcholanthrene. <\/jats:p>","DOI":"10.1139\/y91-065","type":"journal-article","created":{"date-parts":[[2011,4,24]],"date-time":"2011-04-24T08:58:18Z","timestamp":1303635498000},"page":"426-436","source":"Crossref","is-referenced-by-count":5,"title":["Unimpaired induction of drug-metabolizing enzymes in hepatocytes isolated from rats with micronodular cirrhosis"],"prefix":"10.1139","volume":"69","author":[{"given":"Zhenqiang","family":"Wu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Pich\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvie","family":"Valli\u00e8res","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre-Michel","family":"Huet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marielle","family":"Gascon-Barr\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"155","container-title":["Canadian Journal of Physiology and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nrcresearchpress.com\/doi\/pdf\/10.1139\/y91-065","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,1,5]],"date-time":"2020-01-05T15:23:28Z","timestamp":1578237808000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.nrcresearchpress.com\/doi\/10.1139\/y91-065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1991,3,1]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1991,3,1]]}},"alternative-id":["10.1139\/y91-065"],"URL":"https:\/\/doi.org\/10.1139\/y91-065","relation":{},"ISSN":["0008-4212","1205-7541"],"issn-type":[{"value":"0008-4212","type":"print"},{"value":"1205-7541","type":"electronic"}],"subject":[],"published":{"date-parts":[[1991,3,1]]}}}