{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T05:37:28Z","timestamp":1760852248002},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,12,13]],"date-time":"2006-12-13T00:00:00Z","timestamp":1165968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2007,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Administration of ethinyl estradiol (EE), a widely used component of oral contraceptives, has been associated with impairment of bile flow and the capacity to excrete organic anions in man and experimental animals. <jats:italic>\u03b1<\/jats:italic>\u2010Asarone (2,4,5\u2010trimethoxypropenylbenzene) and 2\u2010methoxy\u20104\u2010(2\u2010propenyl) phenoxyacetic acid (MPPA) have shown hypolipidemic effects. In addition to these effects, we decided to evaluate the properties of these compounds on EE\u2010induced cholestasis. Wistar male rats were injected subcutaneously with 10\u2003mg\/kg of EE for 5\u2003days; simultaneously, <jats:italic>\u03b1<\/jats:italic>\u2010asarone or MPPA were also administered and appropriate controls were performed. <jats:italic>\u03b1<\/jats:italic>\u2010asarone and MPPA decreased plasma and bile cholesterol. EE diminished triglycerides total, low\u2010density lipoprotein, high\u2010density lipoprotein and bile cholesterol. MPPA further decreased these lipid parameters. Alkaline phosphatase (an enzyme marker of cholestasis) was increased after administration of EE, but this effect was prevented significantly by <jats:italic>\u03b1<\/jats:italic>\u2010asarone or MPPA administration. Bile flow was importantly decreased by EE and increased by <jats:italic>\u03b1<\/jats:italic>\u2010asarone alone. Furthermore, <jats:italic>\u03b1<\/jats:italic>\u2010asarone or MPPA preserved the normal bile flow in EE\u2010treated rats. EE inhibited the activity of the Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup>\u2010ATPase, while both <jats:italic>\u03b1<\/jats:italic>\u2010asarone and MPPA preserved this enzyme activity. Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup>\u2010ATPase is involved in Na<jats:sup>+<\/jats:sup>\u2010coupled uptake of bile acids into hepatocytes and, therefore, ultimately is the driving force for the generation of bile flow. Therefore, the anticholestatic effects of <jats:italic>\u03b1<\/jats:italic>\u2010asarone and MPPA, described herein by the first time, may be due to its ability to preserve ATPase activity. This enzyme is negatively regulated by membrane cholesterol, thus the hypolipidemic effects of the compounds tested may be responsible for Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup>\u2010ATPase activity and bile flow maintenance.<\/jats:p>","DOI":"10.1111\/j.1472-8206.2006.00453.x","type":"journal-article","created":{"date-parts":[[2006,12,14]],"date-time":"2006-12-14T06:40:26Z","timestamp":1166078426000},"page":"81-88","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effect of <i>\u03b1<\/i>\u2010asarone and a derivative on lipids, bile flow and Na<sup>+<\/sup>\/K<sup>+<\/sup>\u2010ATPase in ethinyl estradiol\u2010induced cholestasis in the rat"],"prefix":"10.1111","volume":"21","author":[{"given":"Leticia","family":"Gardu\u00f1o\u2010Siciliano","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Labarrios","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joaqu\u00edn","family":"Tamariz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario G.","family":"Moreno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Germ\u00e1n","family":"Chamorro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Muriel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,12,18]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199810223391707"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1007226"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840030422"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1665-2681(19)32126-X"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0031-9422(80)83029-9"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-8741(96)01492-4"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-959625"},{"key":"e_1_2_7_9_2","first-page":"535","article-title":"Synthesis and hypolipidemic activity of modified side chain alpha\u2010asarone homologues","volume":"51","author":"Cruz A.","year":"2001","journal-title":"Arzneimittelforschung"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1211\/0022357991772015"},{"key":"e_1_2_7_11_2","first-page":"269","volume-title":"Methods of enzymatic analysis","author":"Bergmeyer H.U.","year":"1983"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.8.2.413"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.98.3.991"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj1460375"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/niox.2000.0285"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116511"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/jat.2550100409"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(66)08014-5"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(76)90492-2"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(82)90213-1"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70425-2"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1996.271.6.G1043"},{"key":"e_1_2_7_23_2","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/S0022-2275(20)33344-7","article-title":"Differential effects of 17alpha\u2010ethinylestradiol on the neutral and acidic pathways of bile salt synthesis in the rat","volume":"40","author":"Koopen N. 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