{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T07:49:51Z","timestamp":1773906591229,"version":"3.50.1"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":822,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:bold>The sea lamprey (<\/jats:bold>\n                      <jats:bold>Petromyzon marinus<\/jats:bold>\n                      <jats:bold>) is a genetically programmed animal model for biliary atresia, as it loses its bile ducts and gallbladder during metamorphosis. However, in contrast to patients with biliary atresia or other forms of cholestasis who develop progressive disease, the postmetamorphosis lampreys grow normally to adult size. To understand how the adult lamprey thrives without the ability to secrete bile, we examined bile salt homeostasis in larval and adult lampreys. Adult livers were severely cholestatic, with levels of bile salts &gt;1 mM, but no evidence of necrosis, fibrosis, or inflammation. Interestingly, both larvae and adults had normal plasma levels (\u02dc10 \u03bcM) of bile salts. In larvae, petromyzonol sulfate (PZS) was the predominant bile salt, whereas the major bile salts in adult liver were sulfated C27 bile alcohols. Cytotoxicity assays revealed that PZS was highly toxic. Pharmacokinetic studies in free-swimming adults revealed that \u02dc35% of intravenously injected bromosulfophthalein (BSP) was eliminated over a 72-hour period. Collection of urine and feces demonstrated that both endogenous and exogenous organic anions, including biliverdin, bile salts, and BSP, were predominantly excreted by way of the kidney, with minor amounts also detected in feces. Gene expression analysis detected marked up-regulation of orthologs of known organic anion and bile salt transporters in the kidney, with lesser effects in the intestine and gills in adults compared to larvae. These findings indicate that adult lampreys tolerate cholestasis by altering hepatic bile salt composition, while maintaining normal plasma bile salt levels predominantly through renal excretion of bile products. Therefore, we conclude that strategies to accelerate renal excretion of bile salt and other toxins should be beneficial for patients with cholestasis.<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.26161","type":"journal-article","created":{"date-parts":[[2012,11,23]],"date-time":"2012-11-23T04:19:27Z","timestamp":1353644367000},"page":"2418-2426","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":34,"title":["Adult sea lamprey tolerates biliary atresia by altering bile salt composition and renal excretion"],"prefix":"10.1097","volume":"57","author":[{"given":"Shi-Ying","family":"Cai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dani\u00ebl A.","family":"Lionarons","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee","family":"Hagey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol J.","family":"Soroka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"Mennone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James L.","family":"Boyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-35-20241201","doi-asserted-by":"crossref","first-page":"225246","DOI":"10.1002\/jmor.1051780303","article-title":"Morphological changes in the liver of the sea lamprey, Petromyzon marinus L., during metamorphosis. II. Canalicular degeneration and transformation of the hepatocytes.","volume":"178","author":"Sidon","year":"1983","journal-title":"J Morphol"},{"key":"R2-35-20241201","doi-asserted-by":"crossref","first-page":"109124","DOI":"10.1002\/jmor.1051770109","article-title":"Morphological changes in the liver of the sea lamprey, Petromyzon marinus L., during metamorphosis: I. Atresia of the bile ducts.","volume":"177","author":"Sidon","year":"1983","journal-title":"J Morphol"},{"key":"R3-35-20241201","first-page":"197255","article-title":"Biliary atresia in lampreys.","volume":"37","author":"Youson","year":"1993","journal-title":"Adv Vet Sci Comp Med"},{"key":"R4-35-20241201","doi-asserted-by":"crossref","first-page":"221235","DOI":"10.1007\/s00427-008-0208-1","article-title":"The lamprey in evolutionary studies.","volume":"218","author":"Osorio","year":"2008","journal-title":"Dev Genes Evol"},{"key":"R5-35-20241201","doi-asserted-by":"crossref","first-page":"701710","DOI":"10.1016\/0300-9629(88)90953-X","article-title":"Tissue levels of bilirubin and biliverdin in the sea lamprey, Petromyzon marinus L., before and after biliary atresia.","volume":"91","author":"Makos","year":"1988","journal-title":"Comp Biochem Physiol A Comp Physiol"},{"key":"R6-35-20241201","doi-asserted-by":"crossref","first-page":"138141","DOI":"10.1126\/science.1067797","article-title":"Bile acid secreted by male sea lamprey that acts as a sex pheromone.","volume":"296","author":"Li","year":"2002","journal-title":"Science"},{"key":"R7-35-20241201","doi-asserted-by":"crossref","first-page":"1141911424","DOI":"10.1073\/pnas.1203008109","article-title":"Intestinal synthesis and secretion of bile salts as an adaptation to developmental biliary atresia in the sea lamprey.","volume":"109","author":"Yeh","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R8-35-20241201","doi-asserted-by":"crossref","first-page":"6774","DOI":"10.1111\/j.1365-2362.1976.tb00495.x","article-title":"Bile salt glucuronides: identification and quantitative analysis in the urine of patients with cholestasis.","volume":"6","author":"Frohling","year":"1976","journal-title":"Eur J Clin Invest"},{"key":"R9-35-20241201","doi-asserted-by":"crossref","first-page":"545553","DOI":"10.1016\/S0016-5085(75)80094-1","article-title":"Sulfated and nonsulfated bile acids in urine, serum, and bile of patients with hepatobiliary diseases.","volume":"68","author":"Makino","year":"1975","journal-title":"Gastroenterology"},{"key":"R10-35-20241201","doi-asserted-by":"crossref","first-page":"104109","DOI":"10.1007\/BF02806931","article-title":"Urinary concentrations of bile acid glucuronides and sulfates in hepatobiliary diseases.","volume":"19","author":"Takikawa","year":"1984","journal-title":"Gastroenterol Jpn"},{"key":"R13-35-20241201","doi-asserted-by":"crossref","first-page":"254256","DOI":"10.1016\/S0016-5085(76)80019-4","article-title":"Selective hepatic uptake and biliary excretion of 35Ssulfobromophthalein in marine elasmobranchs.","volume":"70","author":"Boyer","year":"1976","journal-title":"Gastroenterology"},{"key":"R14-35-20241201","doi-asserted-by":"crossref","first-page":"974981","DOI":"10.1152\/ajplegacy.1976.230.4.974","article-title":"Biliary secretion in elasmobranchs. 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Hepatic uptake and biliary excretion of organic anions.","volume":"230","author":"Boyer","year":"1976","journal-title":"Am J Physiol"},{"key":"R15-35-20241201","doi-asserted-by":"crossref","first-page":"G762G768","DOI":"10.1152\/ajpgi.00424.2003","article-title":"Lack of biliary lipid excretion in the little skate, Raja erinacea, indicates the absence of functional Mdr2, Abcg5, and Abcg8 transporters.","volume":"286","author":"Elferink","year":"2004","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"R17-35-20241201","doi-asserted-by":"crossref","first-page":"5869","DOI":"10.1111\/j.1478-3231.2011.02662.x","article-title":"Effect of bile duct ligation on bile acid composition in mouse serum and liver.","volume":"32","author":"Zhang","year":"2012","journal-title":"Liver Int"},{"key":"R18-35-20241201","first-page":"861869","article-title":"Sulphated and unsulphated bile acids in serum, bile, and urine of patients with cholestasis.","volume":"17","author":"van Berge","year":"1976","journal-title":"Gut"},{"key":"R19-35-20241201","doi-asserted-by":"crossref","first-page":"186195","DOI":"10.1016\/j.yjmcc.2010.04.011","article-title":"Conversion of biliverdin to bilirubin by biliverdin reductase contributes to endothelial cell protection by heme oxygenase1evidence for direct and indirect antioxidant actions of bilirubin.","volume":"49","author":"Jansen","year":"2010","journal-title":"J Mol Cell Cardiol"},{"key":"R20-35-20241201","doi-asserted-by":"crossref","first-page":"51715176","DOI":"10.1073\/pnas.0813132106","article-title":"Bilirubin and glutathione have complementary antioxidant and cytoprotective roles.","volume":"106","author":"Sedlak","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R21-35-20241201","doi-asserted-by":"crossref","first-page":"275292","DOI":"10.1007\/BF00315633","article-title":"Differentiation of the segmented tubular nephron and excretory duct during lamprey metamorphosis.","volume":"169","author":"Youson","year":"1984","journal-title":"Anat Embryol (Berl)"},{"key":"R22-35-20241201","doi-asserted-by":"crossref","first-page":"611620","DOI":"10.1007\/s00424-006-0152-8","article-title":"The bile salt export pump.","volume":"453","author":"Stieger","year":"2007","journal-title":"Pflugers Arch"},{"key":"R23-35-20241201","doi-asserted-by":"crossref","first-page":"1259812605","DOI":"10.1021\/bi050943e","article-title":"Bile acid transport in sister of Pglycoprotein (ABCB11) knockout mice.","volume":"44","author":"Lam","year":"2005","journal-title":"Biochemistry"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.26161","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201306000-00035","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T09:12:07Z","timestamp":1733044327000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201306000-00035"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6]]},"references-count":20,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2013]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.26161","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718049490.793481242","asserted-by":"object"}]},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2013,6]]}}}