{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T19:55:39Z","timestamp":1740167739837,"version":"3.37.3"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T00:00:00Z","timestamp":1695427200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T00:00:00Z","timestamp":1695427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81371511","8220141866"],"award-info":[{"award-number":["81371511","8220141866"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pharmacol Toxicol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Objectives<\/jats:title>\n                <jats:p>Our previous clinical trial showed that etomidate requirements to reach an appropriate level of anesthesia in patients with obstructive jaundice were reduced, which means that these patients are more sensitive to etomidate. However, the mechanism is still not completely clear. The present study was aimed to investigate the mechanism by which bilirubin facilitates etomidate induced sedation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A bile duct ligation (BDL) rat model was used to simulate obstructive jaundice. Anesthesia sensitivity to etomidate was determined by the time to loss of righting reflex (LORR). Intrathecal injection of bilirubin was used to test the effects of bilirubin on etomidate induced sedation. The modulating effects of bilirubin on GABA responses were studied using the whole-cell patch clamp technique.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The time to LORR induced by etomidate was significantly decreased in the BDL groups (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), and unconjugated bilirubin in serum and cerebrospinal fluid (CSF) were markedly increased (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). The time to LORR induced by etomidate was decreased after intrathecal injection of bilirubin (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). A bilirubin concentration of 1.0\u00a0\u03bcM increased the GABA-induced currents of rat cortical pyramidal neurons (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Furthermore, 1.0\u00a0\u03bcM bilirubin enhanced GABA-induced currents modulated by etomidate (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our results demonstrated that pathologic bilirubin in CSF could enhance etomidate induced sedation. The mechanism may be that bilirubin increase the GABA-induced currents of rat pyramidal neurons.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40360-023-00675-w","type":"journal-article","created":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T01:02:18Z","timestamp":1695430938000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bilirubin potentiates etomidate-induced sedation by enhancing GABA-induced currents after bile duct ligation"],"prefix":"10.1186","volume":"24","author":[{"given":"Hao","family":"Gao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian-Gang","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guo-Xia","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Feng","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-Fu","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2127-4046","authenticated-orcid":false,"given":"Jin-Chao","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,9,23]]},"reference":[{"issue":"11","key":"675_CR1","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1681\/ASN.V5111853","volume":"5","author":"J Green","year":"1995","unstructured":"Green J, Better OS. 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The use and handling of experimental animals were carried out in accordance with the relevant regulations of the State and the Experimental Animal Center of the Second Military Medical University. The study protocol was approved by our local ethics committee (approval date 10.03.2016).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that there are no potential conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"46"}}