{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:30:51Z","timestamp":1787614251612,"version":"build-2736575974"},"reference-count":83,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T00:00:00Z","timestamp":1624320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2013\/09\/B\/NZ4\/00536"],"award-info":[{"award-number":["2013\/09\/B\/NZ4\/00536"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2015\/19\/B\/NZ4\/01902"],"award-info":[{"award-number":["2015\/19\/B\/NZ4\/01902"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute liver failure (ALF) is associated with deregulated nitric oxide (NO) signaling in the brain, which is one of the key molecular abnormalities leading to the neuropsychiatric disorder called hepatic encephalopathy (HE). This study focuses on the effect of ALF on the relatively unexplored endothelial NOS isoform (eNOS). The cerebral prefrontal cortices of rats with thioacetamide (TAA)-induced ALF showed decreased eNOS expression, which resulted in an overall reduction of NOS activity. ALF also decreased the content of the NOS cofactor, tetrahydro-L-biopterin (BH4), and evoked eNOS uncoupling (reduction of the eNOS dimer\/monomer ratio). The addition of the NO precursor L-arginine in the absence of BH4 potentiated ROS accumulation, whereas nonspecific NOS inhibitor L-NAME or EDTA attenuated ROS increase. The ALF-induced decrease of eNOS content and its uncoupling concurred with, and was likely causally related to, both increased brain content of reactive oxidative species (ROS) and decreased cerebral cortical blood flow (CBF) in the same model.<\/jats:p>","DOI":"10.3390\/ijms22136662","type":"journal-article","created":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T13:02:10Z","timestamp":1624366930000},"page":"6662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Decreased Expression and Uncoupling of Endothelial Nitric Oxide Synthase in the Cerebral Cortex of Rats with Thioacetamide-Induced Acute Liver Failure"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9743-2683","authenticated-orcid":false,"given":"Krzysztof","family":"Milewski","sequence":"first","affiliation":[{"name":"Department of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawi\u0144skiego Str, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4235-2963","authenticated-orcid":false,"given":"Anna Maria","family":"Czarnecka","sequence":"additional","affiliation":[{"name":"Department of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawi\u0144skiego Str, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6063-6228","authenticated-orcid":false,"given":"Jan","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Department of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawi\u0144skiego Str, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7388-3092","authenticated-orcid":false,"given":"Magdalena","family":"Zieli\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawi\u0144skiego Str, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/nrgastro.2010.116","article-title":"Mechanisms, diagnosis and management of hepatic encephalopathy","volume":"7","author":"Prakash","year":"2010","journal-title":"Nat. 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