{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T05:50:24Z","timestamp":1777441824375,"version":"3.51.4"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,11,24]],"date-time":"2014-11-24T00:00:00Z","timestamp":1416787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["386569-2010"],"award-info":[{"award-number":["386569-2010"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2015,1]]},"abstract":"Background and Purpose<\/jats:title>Erythropoietin (EPO<\/jats:styled-content>) is used to treat anaemia associated with chronic kidney disease (CKD<\/jats:styled-content>). Hypoxia is associated with anaemia and is known to cause a decrease in cytochromeP<\/jats:styled-content>450 (P<\/jats:styled-content>450) expression. AsEPO<\/jats:styled-content>production is regulated by hypoxia, we investigated the role ofEPO<\/jats:styled-content>onP<\/jats:styled-content>450 expression and function.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>MaleW<\/jats:styled-content>istar rats were subjected to a 0.7% adenine diet for 4 weeks to induceCKD<\/jats:styled-content>. The diet continued for an additional 2 weeks while rats receivedEPO<\/jats:styled-content>by i.p. injection every other day. Following euthanasia, hepaticP<\/jats:styled-content>450mRNA<\/jats:styled-content>and protein expression were determined. Hepatic enzyme activity of selectedP<\/jats:styled-content>450s was determined and chromatin immunoprecipitation was used to characterize binding of nuclear receptors involved in the transcriptional regulation ofCYP<\/jats:styled-content>2C<\/jats:styled-content>andCYP<\/jats:styled-content>3A<\/jats:styled-content>.<\/jats:p><\/jats:sec>Key Results<\/jats:title>EPO<\/jats:styled-content>administration decreased hepaticmRNA<\/jats:styled-content>and protein expression ofCYP<\/jats:styled-content>3A<\/jats:styled-content>2 (P<\/jats:italic><\/jats:styled-content>< 0.05), but notCYP<\/jats:styled-content>2C<\/jats:styled-content>11. Similarly,EPO<\/jats:styled-content>administration decreasedCYP<\/jats:styled-content>3A<\/jats:styled-content>2 protein expression by 81% (P<\/jats:italic><\/jats:styled-content>< 0.001). A 32% decrease (P<\/jats:italic><\/jats:styled-content>< 0.05) in hepaticCYP<\/jats:styled-content>3A<\/jats:styled-content>enzymatic activity (V<\/jats:italic><\/jats:styled-content>max<\/jats:sub>) was observed for the formation of 6\u03b2OH<\/jats:styled-content>\u2010testosterone in theEPO<\/jats:styled-content>\u2010treated group. Decreases inRNA<\/jats:styled-content>polII<\/jats:styled-content>recruitment (P<\/jats:italic><\/jats:styled-content>< 0.01), hepatocyte nuclear factor 4\u03b1<\/jats:styled-content>binding (P<\/jats:italic><\/jats:styled-content>< 0.05) and pregnaneX<\/jats:styled-content>receptor binding (P<\/jats:italic><\/jats:styled-content>< 0.01) to the promoter region ofCYP<\/jats:styled-content>3A<\/jats:styled-content>were also observed inEPO<\/jats:styled-content>\u2010treated rats.<\/jats:p><\/jats:sec>Conclusions and Implications<\/jats:title>Our data show thatEPO<\/jats:styled-content>decreases the expression and function ofCYP<\/jats:styled-content>3A<\/jats:styled-content>, but notCYP<\/jats:styled-content>2C<\/jats:styled-content>in rat liver.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12932","type":"journal-article","created":{"date-parts":[[2014,9,15]],"date-time":"2014-09-15T03:37:25Z","timestamp":1410752245000},"page":"201-213","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Effect of erythropoietin on hepatic cytochromeP<\/scp>450 expression and function in an adenine\u2010fed rat model of chronic kidney disease"],"prefix":"10.1111","volume":"172","author":[{"given":"D A","family":"Feere","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology Western University London ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T J","family":"Velenosi","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Western University London ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B 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