{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T09:34:00Z","timestamp":1787045640719,"version":"build-2736575974"},"reference-count":53,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"the National Council for Scientific and Technological Development\u2014CNPq","doi-asserted-by":"publisher","award":["312114\/2025-7"],"award-info":[{"award-number":["312114\/2025-7"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"award":["312114\/2025-7"],"award-info":[{"award-number":["312114\/2025-7"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Coordination for the Improvement of Higher Education Personnel\u2014CAPES","award":["88881.083661\/2024-01"],"award-info":[{"award-number":["88881.083661\/2024-01"]}]},{"name":"INCT\/Excitotoxicity and Neuroprotection","award":["408446\/2024-2"],"award-info":[{"award-number":["408446\/2024-2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objectives: Acute liver failure (ALF) rapidly induces hepatic encephalopathy (HE), a severe neurological syndrome associated with astrocytic dysfunction and glutamatergic dysregulation. Guanosine (GUO), an endogenous guanine-based nucleoside, has neuroprotective properties, but its effects on astrocyte-associated glutamate regulation in ALF-induced HE remain incompletely understood. This study tested whether GUO attenuates neurological deterioration and glutamatergic dysfunction in an experimental model of ALF-induced HE. Methods: Male Wistar rats underwent 92% subtotal hepatectomy and received intraperitoneal GUO (7.5 mg\/kg) or saline at prespecified time points after surgery. Neurological severity and survival were monitored for 72 h. Astrocytic morphology was assessed by GFAP immunofluorescence. Cerebrospinal fluid (CSF) albumin, glutamate, and glutamine levels, cortical Na+-dependent glutamate uptake, GLAST immunocontent, and the 67 kDa GLT-1 monomer immunocontent were evaluated. Results: Subtotal hepatectomy induced progressive neurological impairment, high mortality, GFAP-associated astrocytic remodeling, increased CSF albumin, glutamate, and glutamine levels, and reduced cortical glutamate uptake. GUO attenuated neurological deterioration and increased 72 h survival from 10.5% to 39.0% (log-rank p = 0.03). GUO also reduced CSF albumin, glutamate, and glutamine concentrations and improved cortical Na+-dependent glutamate uptake without altering GLAST or GLT-1 monomer immunocontent. Conclusions: GUO attenuated astrocyte-associated glutamatergic dysregulation and improved survival in ALF-induced HE. These findings support further mechanistic and translational investigation of GUO as an experimental modulator of astrocyte-associated glutamate handling in ALF-induced HE.<\/jats:p>","DOI":"10.3390\/metabo16080587","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T09:06:41Z","timestamp":1787044001000},"page":"587","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Guanosine Attenuates Astrocyte-Associated Glutamatergic Dysregulation and Improves Survival in Acute Liver Failure-Induced Hepatic Encephalopathy"],"prefix":"10.3390","volume":"16","author":[{"given":"Pedro Arend","family":"Guazzelli","sequence":"first","affiliation":[{"name":"Graduate Program in Biological Sciences: Biochemistry, Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade (ICBS), Universidade Federal do Rio Grande do Sul\u2014UFRGS, Porto Alegre 90035-003, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe dos Santos","family":"Fachim","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Biochemistry, Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade (ICBS), Universidade Federal do Rio Grande do Sul\u2014UFRGS, Porto Alegre 90035-003, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anderson Santos","family":"Travassos","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Biochemistry, Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade (ICBS), Universidade Federal do Rio Grande do Sul\u2014UFRGS, Porto Alegre 90035-003, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine","family":"Nonose","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Biochemistry, Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade (ICBS), Universidade Federal do Rio Grande do Sul\u2014UFRGS, Porto Alegre 90035-003, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9ia Silva","family":"da Rocha","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Biochemistry, Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade (ICBS), Universidade Federal do Rio Grande do Sul\u2014UFRGS, Porto Alegre 90035-003, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9232-7371","authenticated-orcid":false,"given":"Francieli","family":"Rohden","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Biochemistry, Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade (ICBS), Universidade Federal do Rio Grande do Sul\u2014UFRGS, Porto Alegre 90035-003, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda Urruth","family":"Fontella","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Biochemistry, Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade (ICBS), Universidade Federal do Rio Grande do Sul\u2014UFRGS, Porto Alegre 90035-003, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1953-7831","authenticated-orcid":false,"given":"Adriano Martimbianco","family":"de Assis","sequence":"additional","affiliation":[{"name":"Graduate Program in Health and Behaviour, Center of Health Science, Universidade Cat\u00f3lica de Pelotas\u2014UCPel, Pelotas 96015-560, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diogo Onofre","family":"Souza","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Sciences: Biochemistry, Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade (ICBS), Universidade Federal do Rio Grande do Sul\u2014UFRGS, Porto Alegre 90035-003, RS, Brazil"},{"name":"Department of Biochemistry, Universidade Federal do Rio Grande do Sul\u2014UFRGS, Porto Alegre 90035-003, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1097\/AIA.0000000000000141","article-title":"Acute Liver Failure: Review and Update","volume":"55","author":"Bernal","year":"2017","journal-title":"Int. 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