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In this study, male Sprague Dawley rats were intraperitoneally injected with melatonin or the same volume of vehicle at 0 and 24\u2009h after MCT intragastric administration. Next, hematoxylin\u2013eosin staining and electron microscopy were performed to evaluate the hepatic sinusoidal injury of rats. Endothelial cell marker RECA\u20101 was observed by immunohistochemistry. Hepatic oxidative stress was analyzed by detecting malondialdehyde, glutathione S\u2010transferase, and reactive oxygen species. Assessment of liver function was carried out by\u00a0analysis of serum aspartate aminotransferase, alanine aminotransferase, total bilirubin, and albumin levels. Real\u2010time polymerase chain reaction and Western blot analysis were used to identify\u00a0liver Sirtuin\u20103 (SIRT3) and active matrix metallopeptidase 9 (MMP\u20109) expression. Besides, liver sinusoidal endothelial cells (LSECs) were used for the in vitro functional verification experiment. Specifically, liver histology of the melatonin\u2010treated groups showed that the pathological damages caused by MCT were significantly attenuated, total HSOS scores were decreased, and the elevation of serum hyaluronic acid observed in the model group was also reduced. Moreover, melatonin treatment also improved the survival of rats after partial hepatectomy. Administration of melatonin ameliorated MCT\u2010induced LSECs injury, hepatic oxidative stress, and hepatic dysfunction. Furthermore, melatonin treatment increased SIRT3 expression while attenuating MMP\u20109 activity in liver tissues. Cell experiment also demonstrated that SIRT3 might mediate the protective effect of melatonin on LSECs. Collectively, our study provided the potential rationale for the application of melatonin for the prevention of MCT\u2010induced HSOS.<\/jats:p>","DOI":"10.1002\/jbt.23422","type":"journal-article","created":{"date-parts":[[2023,6,25]],"date-time":"2023-06-25T00:41:24Z","timestamp":1687653684000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Melatonin attenuates monocrotaline\u2010induced hepatic sinusoidal obstruction syndrome in rats via activation of Sirtuin\u20103"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8288-699X","authenticated-orcid":false,"given":"Xiaofei","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Gastroenterology The First Affiliated Hospital of Anhui Medical University Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of 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