{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T08:50:53Z","timestamp":1790412653370,"version":"4.1.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2002,2,1]],"date-time":"2002-02-01T00:00:00Z","timestamp":1012521600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2003,12,30]],"date-time":"2003-12-30T00:00:00Z","timestamp":1072742400000},"content-version":"vor","delay-in-days":697,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,2]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>The effect of adrenergic innervation and\/or circulating catecholamines on the function of liver fibrogenic cells is poorly understood. Our aim was to investigate the effects of noradrenergic antagonism on carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)-induced liver fibrosis in rats. Two weeks of CCl<jats:sub>4<\/jats:sub> induced a \u02dc5-fold increase in the area of fibrosis as compared with controls. The addition of 6-hydroxydopamine (OHDA), a toxin that destroys noradrenergic fibers, decreased fibrosis by 60%. After 6 weeks of CCl<jats:sub>4<\/jats:sub>, the area of fibrosis increased about 30-fold in CCl<jats:sub>4<\/jats:sub>-treated animals and was decreased by 36% with OHDA. At 2 weeks, OHDA abrogated the CCl<jats:sub>4<\/jats:sub>-induced increase in mRNA level of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), an inhibitor of extracellular matrix degradation, and it greatly reduced it at 6 weeks. Finally, when rats treated with CCl<jats:sub>4<\/jats:sub> for 2 weeks also received prazosin, an antagonist of \u03b1<jats:sub>1<\/jats:sub>-adrenergic receptors, fibrosis was decreased by 83%. In conclusion, destruction of noradrenergic fibers or antagonism of noradrenergic signaling through \u03b1<jats:sub>1<\/jats:sub> receptors inhibited the development of liver fibrosis. Because adrenoreceptor antagonists have a very sound safety profile, they appear as attractive drugs to reduce liver fibrogenesis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1053\/jhep.2002.31166","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T03:46:10Z","timestamp":1030247170000},"page":"325-331","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":77,"title":["Inhibition of rat liver fibrogenesis through noradrenergic antagonism"],"prefix":"10.1097","volume":"35","author":[{"given":"Liliane","family":"Dubuisson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Desmouli\u00e8re","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Decourt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"Evad\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Bedin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliane","family":"Boussarie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Barrier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Vidaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Rosenbaum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"10.1053\/jhep.2002.31166-BIB1|cit1","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1074\/jbc.275.4.2247","article-title":"Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury","volume":"275","author":"Friedman","year":"2000","journal-title":"J Biol Chem"},{"key":"10.1053\/jhep.2002.31166-BIB2|cit2","first-page":"265","article-title":"Proliferation and phenotypic modulation of portal fibroblasts in the early stages of cholestatic fibrosis in the rat","volume":"74","author":"Tuchweber","year":"1996","journal-title":"Lab Invest"},{"key":"10.1053\/jhep.2002.31166-BIB3|cit3","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/0165-1838(92)90038-I","article-title":"The role of the sympathetic nervous system in promoting liver cirrhosis induced by carbon tetrachloride, using the essential hypertensive animal (SHR)","volume":"37","author":"Hsu","year":"1992","journal-title":"J Auton Nerv Syst"},{"key":"10.1053\/jhep.2002.31166-BIB4|cit4","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1177\/030006059602400603","article-title":"Demonstration of noradrenaline-immunoreactive nerve fibres in the liver","volume":"24","author":"Fukuda","year":"1996","journal-title":"J Int Med Res"},{"key":"10.1053\/jhep.2002.31166-BIB5|cit5","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/j.1474-8673.1990.tb00017.x","article-title":"Effects of sympathetic denervation on liver fibroblasts: prevention by adenosine","volume":"10","author":"Albino-Teixeira","year":"1990","journal-title":"J Auton Pharmacol"},{"key":"10.1053\/jhep.2002.31166-BIB6|cit6","first-page":"142","article-title":"Prostaglandin F2 alpha and D2 release from primary Ito cell cultures after stimulation with noradrenaline and ATP but not adenosine","volume":"20","author":"Athari","year":"1994","journal-title":"Hepatology"},{"key":"10.1053\/jhep.2002.31166-BIB7|cit7","doi-asserted-by":"crossref","first-page":"2771","DOI":"10.1172\/JCI119103","article-title":"Growth inhibitory properties of endothelin-1 in activated human hepatic stellate cells: a cyclic adenosine monophosphate-mediated pathway. 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