{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:33:07Z","timestamp":1791289987420,"version":"4.3.0"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,2]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract.<\/jats:title>\n                    <jats:p>\n                      Chronic renal failure (CRF) is associated with a decrease in drug metabolism. The mechanism remains poorly understood. The present study investigated the repercussions of CRF on liver cytochrome P450 (CYP450). Three groups of rats were defined: control, control paired-fed, and CRF. Total CYP450 activity, protein expression of several CYP450 isoforms as well as their mRNA, and the\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      N-demethylation of erythromycin were assessed in liver microsomes. The regulation of liver CYP450 by dexamethasone and phenobarbital was assessed in CRF rats. Compared with control and control paired-fed rats, creatinine clearance was reduced by 60% (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.01) in CRF rats. Weight was reduced by 30% (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.01) in control paired-fed and CRF rats, compared with control animals. There was no difference in the CYP450 parameters between control and control paired-fed. Compared with control paired-fed rats, total CYP450 was reduced by 47% (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001) in CRF rats. Protein expression of CYP2C11, CYP3A1, and CYP3A2 were considerably reduced (&gt;40%,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001) in rats with CRF. The levels of CYP1A2, CYP2C6, CYP2D, and CYP2E1 were the same in the three groups. Northern blot analysis revealed a marked downregulation in gene expression of CYP2C11, 3A1, and 3A2 in CRF rats. Although liver CYP450 was reduced in CRF, its induction by dexamethasone and phenobarbital was present. N-demethylation of erythromycin was decreased by 50% in CRF rats compared with control (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001). In conclusion, CRF in rats is associated with a decrease in liver cytochrome P450 activity (mainly in CYP2C11, CYP3A1, and 3A2), secondary to reduced gene expression.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.v122326","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T13:08:48Z","timestamp":1619442528000},"page":"326-332","source":"Crossref","is-referenced-by-count":180,"title":["Downregulation of Hepatic Cytochrome P450 in Chronic Renal Failure"],"prefix":"10.1681","volume":"12","author":[{"given":"FRANCOIS","family":"LEBLOND","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CARL","family":"GU\u00c9VIN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CHRISTIAN","family":"DEMERS","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ISABELLE","family":"PELLERIN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MARIELLE","family":"GASCON-BARR\u00c9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"VINCENT","family":"PICHETTE","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/00001751-200102000-00013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:27:34Z","timestamp":1786130854000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/00001751-200102000-00013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,2]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2001]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.v122326","relation":{},"ISSN":["1046-6673"],"issn-type":[{"value":"1046-6673","type":"print"}],"subject":[],"published":{"date-parts":[[2001,2]]}}}