{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T12:39:44Z","timestamp":1775911184589,"version":"3.50.1"},"reference-count":84,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T00:00:00Z","timestamp":1711670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Merit Review from the Department of Veterans\u2019 Affairs (MDN)"},{"name":"Stanley J. Glaser Research"},{"name":"AASLD\/American Liver Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Hepatic encephalopathy (HE) is a neurological condition linked to liver failure. Acute HE (Type A) occurs with acute liver failure, while chronic HE (Type C) is tied to cirrhosis and portal hypertension. HE treatments lag due to gaps in understanding its development by gender and age. We studied how sex and age impact HE and its severity with combined liver toxins. Our findings indicate that drug-induced (thioacetamide, TAA) brain edema was more severe in aged males than in young males or young\/aged female rats. However, adding alcohol (ethanol, EtOH) worsens TAA\u2019s brain edema in both young and aged females, with females experiencing a more severe effect than males. These patterns also apply to Type A HE induced by azoxymethane (AZO) in mice. Similarly, TAA-induced behavioral deficits in Type C HE were milder in young and aged females than in males. Conversely, EtOH and TAA in young\/aged males led to severe brain edema and fatality without noticeable behavioral changes. TAA metabolism was slower in aged males than in young or middle-aged rats. When TAA-treated aged male rats received EtOH, there was a slow and sustained plasma level of thioacetamide sulfoxide (TASO). This suggests that with EtOH, TAA-induced HE is more severe in aged males. TAA metabolism was similar in young, middle-aged, and aged female rats. However, with EtOH, young and aged females experience more severe drug-induced HE as compared to middle-aged adult rats. These findings strongly suggest that gender and age play a role in the severity of HE development and that the presence of one or more liver toxins may aggravate the severity of the disease progression.<\/jats:p>","DOI":"10.3390\/biology13040228","type":"journal-article","created":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T13:32:56Z","timestamp":1711891976000},"page":"228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Age and Sex in the Development of Hepatic Encephalopathy: Role of Alcohol"],"prefix":"10.3390","volume":"13","author":[{"given":"Xiao","family":"Tong","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hussain","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Infectious Disease, Larkin Community Hospital, Miami, FL 33143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nagarajarao","family":"Shamaladevi","sequence":"additional","affiliation":[{"name":"Molecular Analytics, Miami, FL 33187, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Norenberg","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"General Medical Research, Neuropathology Section, R&D Service, Veterans Affairs Medical Center, Miami, FL 33125, USA"},{"name":"South Florida VA Foundation for Research and Education Inc., Veterans Affairs Medical Center, Miami, FL 33125, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aya","family":"Fadel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ocean Medical Center-Hackensack Meridian Health, Brick, NJ 08724, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0581-4164","authenticated-orcid":false,"given":"Omar","family":"El Hiba","sequence":"additional","affiliation":[{"name":"Laboratory of Anthropogenic, Biotechnology, Health, and Nutritional Physiopathologies, Neuroscience and Toxicology Team, Faculty of Sciences, Chouaib Doukkali University, Av. Des Facult\u00e9s, El Jadida 24000, Morocco"},{"name":"Hassan First University of Settat, Higher Institute of Health Sciences, Laboratory of Sciences and Health Technologies, Epidemiology and Biomedical Unit, Settat 26000, Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2068-7079","authenticated-orcid":false,"given":"El","family":"Abdeljalil","sequence":"additional","affiliation":[{"name":"Hassan First University of Settat, Higher Institute of Health Sciences, Laboratory of Sciences and Health Technologies, Epidemiology and Biomedical Unit, Settat 26000, Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2583-7515","authenticated-orcid":false,"given":"Bilal","family":"El-Mansoury","sequence":"additional","affiliation":[{"name":"Laboratory of Anthropogenic, Biotechnology, Health, and Nutritional Physiopathologies, Neuroscience and Toxicology Team, Faculty of Sciences, Chouaib Doukkali University, Av. Des Facult\u00e9s, El Jadida 24000, Morocco"},{"name":"Hassan First University of Settat, Higher Institute of Health Sciences, Laboratory of Sciences and Health Technologies, Epidemiology and Biomedical Unit, Settat 26000, Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4292-3096","authenticated-orcid":false,"given":"Deepak","family":"Kempuraj","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medicine, University of Missouri, Columbia, MO 65211, USA"},{"name":"U.S. Department of Veterans Affairs, Harry S. Truman Memorial Veterans Hospital, Columbia, MO 65201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9237-5501","authenticated-orcid":false,"given":"Sampath","family":"Natarajan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur 613401, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Schally","sequence":"additional","affiliation":[{"name":"General Medical Research, Neuropathology Section, R&D Service, Veterans Affairs Medical Center, Miami, FL 33125, USA"},{"name":"South Florida VA Foundation for Research and Education Inc., Veterans Affairs Medical Center, Miami, FL 33125, USA"},{"name":"Pathology, Laboratory Medicine, Endocrine, Polypeptide and Cancer Institute, Department of Veterans Affairs, Miami, FL 33125, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miklos","family":"Jaszberenyi","sequence":"additional","affiliation":[{"name":"General Medical Research, Neuropathology Section, R&D Service, Veterans Affairs Medical Center, Miami, FL 33125, USA"},{"name":"South Florida VA Foundation for Research and Education Inc., Veterans Affairs Medical Center, Miami, FL 33125, USA"},{"name":"Department of Pathophysiology, Faculty of Medicine, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Salgueiro","sequence":"additional","affiliation":[{"name":"General Medical Research, Neuropathology Section, R&D Service, Veterans Affairs Medical Center, Miami, FL 33125, USA"},{"name":"South Florida VA Foundation for Research and Education Inc., Veterans Affairs Medical Center, Miami, FL 33125, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Paidas","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology & Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2115-7860","authenticated-orcid":false,"given":"Arumugam","family":"Jayakumar","sequence":"additional","affiliation":[{"name":"General Medical Research, Neuropathology Section, R&D Service, Veterans Affairs Medical Center, Miami, FL 33125, USA"},{"name":"South Florida VA Foundation for Research and Education Inc., Veterans Affairs Medical Center, Miami, FL 33125, USA"},{"name":"Department of Obstetrics, Gynecology & Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.12968\/hmed.2012.73.2.79","article-title":"Hepatic encephalopathy","volume":"73","author":"Patel","year":"2012","journal-title":"Br. 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