{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:31:00Z","timestamp":1787563860055,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T00:00:00Z","timestamp":1669248000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001424","name":"American Liver Foundation","doi-asserted-by":"publisher","award":["Postdoctoral Research Fellowship"],"award-info":[{"award-number":["Postdoctoral Research Fellowship"]}],"id":[{"id":"10.13039\/100001424","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic intraperitoneal injection of thioacetamide (TAA) in rats has been used as an animal model of human cirrhosis to study the effects of the disease on drug metabolism. However, TAA inhibits P450 enzymes directly and independently of cirrhosis. We investigated the effects of chronic cirrhosis in rats, induced by 10\u2009weeks of intraperitoneal TAA, on the P450 enzymes after a 10\u2010day washout period to eliminate TAA. Liver histology and serum biomarkers of hepatic function confirmed cirrhosis in all animals. Microsomal total P450 content, P450 reductase activity and ethoxycoumarin O\u2010deethylase activity, a general marker of P450 activity, were significantly reduced by 30%\u201350% in cirrhotic animals. Additionally, the protein content and Michaelis\u2013Menten kinetics of the activities of CYP2D, CYP2E1 and CYP3A were investigated. Whereas cirrhosis reduced the microsomal protein contents of CYP2D and CYP3A by 70% and 30%, respectively, the protein contents of CYP2E1 were not affected. However, the activities of all the tested isoenzymes were substantially lower in the cirrhotic livers. It is concluded that the TAA model of cirrhosis that incorporates a 10\u2010day washout period after intraperitoneal injection of the chemical to rats produces isoenzyme\u2010selective reductions in the P450 proteins or activities, which are independent of the direct inhibitory effects of TAA.<\/jats:p>","DOI":"10.1111\/bcpt.13813","type":"journal-article","created":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T09:33:38Z","timestamp":1668245618000},"page":"197-210","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Effects of chronic cirrhosis induced by intraperitoneal thioacetamide injection on the protein content and Michaelis\u2013Menten kinetics of cytochrome P450 enzymes in the rat liver microsomes"],"prefix":"10.1111","volume":"132","author":[{"given":"Devaraj Venkatapura","family":"Chandrashekar","sequence":"first","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences School of Pharmacy, Chapman University  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barent N.","family":"DuBois","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences School of Pharmacy, Chapman University  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamunur","family":"Rashid","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences School of Pharmacy, Chapman University  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1770-0391","authenticated-orcid":false,"given":"Reza","family":"Mehvar","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences School of Pharmacy, Chapman University  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.16831"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010002\u20100474\u20101"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010003\u20100586\u20102"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010022\u201001119\u20100"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2020.1702022"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010008\u20100553\u2010z"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010013\u20101502\u2010z"},{"key":"e_1_2_7_9_1","first-page":"9","article-title":"A novel chronic cirrhosis TAA\u2010induced model in rats","volume":"3","author":"Guerra RR","year":"2010","journal-title":"Braz J Vet Pathol"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/0023677215573040"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168\u20103659(02)00463\u20107"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00199.2012"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2013.08.015"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.120615"},{"key":"e_1_2_7_15_1","first-page":"8","article-title":"Rodent models of alcoholic liver disease: role of binge ethanol administration","author":"Ghosh Dastidar S","year":"2018","journal-title":"Biomolecules"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102362.2006.01620.x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02307309"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026228018643"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.111.043539"},{"issue":"1","key":"e_1_2_7_20_1","first-page":"36","article-title":"Nicotine metabolism in liver microsomes from rats with acute hepatitis or cirrhosis","volume":"26","author":"Nakajima M","year":"1998","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10238\u2010001\u20108005\u20104"},{"issue":"2","key":"e_1_2_7_22_1","first-page":"439","article-title":"Thioacetamide\u2010induced hepatic necrosis. 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