{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T18:50:05Z","timestamp":1788893405740,"version":"build-2803163510"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T00:00:00Z","timestamp":1585612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81720108033"],"award-info":[{"award-number":["81720108033"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,16]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>To investigate the effect of ethanol intake on the whole enterohepatic circulation (EHC) of bile acids (BAs) and, more importantly, on pharmacokinetics of irinotecan.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The present study utilized a mouse model administered by gavage with 0 (control), 240\u00a0mg\/100\u00a0g (30%, v\/v) and 390\u00a0mg\/100\u00a0g (50%, v\/v) ethanol for 6\u00a0weeks, followed by BA profiles in the whole EHC (including liver, gallbladder, intestine and plasma) and colon using ultra-high performance liquid chromatography with tandem mass spectrometry analysis. Pharmacokinetic parameters of irinotecan were measured after administration of irinotecan (i.v. 5\u00a0mg\/kg) on alcohol-treated mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results showed that compared with the control group, concentrations of most free-BAs, total amount of the three main forms of BAs (free-BA, taurine-BA and glycine-BA) and total BAs (TBAs) in 50% ethanol intake group were significantly increased, which are mostly attributed to the augmentation of free-BAs and taurine-BAs. Additionally, the TBAs in liver and gallbladder and the BA pool were markedly increased in the 30% ethanol intake group. Importantly, ethanol intake upregulated the expression of BA-related enzymes (Cyp7a1, Cyp27a1, Cyp8b1 and Baat) and transporters (Bsep, Mrp2, P-gp and Asbt) and downregulated the expression of transporter Ntcp and nuclear receptor Fxr in the liver and ileum, respectively. Additionally, 50% ethanol intake caused fairly distinct liver injury. Furthermore, the AUC0\u201324 h of irinotecan and SN38 were significantly reduced but their clearance was significantly increased in the disrupted EHC of BA by 50% ethanol intake.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present study demonstrated that ethanol intake altered the expression of BA-related synthetases and transporters. The BA levels, especially the toxic BAs (chenodeoxycholic acid, deoxycholic acid and lithocholic acid), in the whole EHC were significantly increased by ethanol intake, which may provide a potential explanation to illuminate the pathogenesis of alcoholic liver injury. Most importantly, chronic ethanol consumption had a significant impact on the pharmacokinetics (AUC0\u201324 h and clearance) of irinotecan and SN38; hence colon cancer patients with chronic alcohol consumption treated with irinotecan deserve our close attention.<\/jats:p><\/jats:sec>","DOI":"10.1093\/alcalc\/agaa005","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T20:08:55Z","timestamp":1579637335000},"page":"264-277","source":"Crossref","is-referenced-by-count":39,"title":["Chronic Alcohol Consumption Increased Bile Acid Levels in Enterohepatic Circulation and Reduced Efficacy of Irinotecan"],"prefix":"10.1093","volume":"55","author":[{"given":"Xia","family":"Gong","sequence":"first","affiliation":[{"name":"232 Waihuan Donglu, Guangzhou Daxuecheng, Panyu District, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qisong","family":"Zhang","sequence":"first","affiliation":[{"name":"232 Waihuan Donglu, Guangzhou Daxuecheng, Panyu District, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjiao","family":"Ruan","sequence":"first","affiliation":[{"name":"232 Waihuan Donglu, Guangzhou Daxuecheng, Panyu District, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Hu","sequence":"first","affiliation":[{"name":"232 Waihuan Donglu, Guangzhou Daxuecheng, Panyu District, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, PR China"},{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Huston, 1441 Moursund St., Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongqiu","family":"Liu","sequence":"first","affiliation":[{"name":"232 Waihuan Donglu, Guangzhou Daxuecheng, Panyu District, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3218-8952","authenticated-orcid":false,"given":"Lingzhi","family":"Gong","sequence":"first","affiliation":[{"name":"232 Waihuan Donglu, Guangzhou Daxuecheng, Panyu District, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,3,31]]},"reference":[{"key":"2020050408575504700_ref1","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1007\/s11095-007-9289-1","article-title":"Bile acid transporters: Structure, function, regulation and pathophysiological implications","volume":"24","author":"Alrefai","year":"2007","journal-title":"Pharm Res"},{"key":"2020050408575504700_ref2","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1002\/hep.20090","article-title":"Cellular regulation of hepatic bile acid transport in health and cholestasis","volume":"39","author":"Anwer","year":"2004","journal-title":"Hepatology"},{"key":"2020050408575504700_ref3","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0014-5793(91)80382-D","article-title":"Ethanol has an acute effect on bile acid biosynthesis in man","volume":"281","author":"Axelson","year":"1991","journal-title":"FEBS Lett"},{"key":"2020050408575504700_ref4","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.ejps.2008.12.005","article-title":"Effect of P-glycoprotein inhibitor, verapamil, on oral bioavailability and pharmacokinetics of irinotecan in rats","volume":"36","author":"Bansal","year":"2009","journal-title":"Eur J Pharm Sci"},{"key":"2020050408575504700_ref5","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jchromb.2016.02.012","article-title":"Development and validation of an UPLC-MS\/MS method for the quantification of irinotecan, SN-38 and SN-38 glucuronide in plasma, urine, feces, liver and kidney: Application to a pharmacokinetic study of irinotecan in rats","volume":"1015-1016","author":"Basu","year":"2016","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"2020050408575504700_ref6","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1172\/JCI106763","article-title":"Interruption of the enterohepatic circulation of digitoxin by cholestyramine. 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