{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T18:32:39Z","timestamp":1769538759562,"version":"3.49.0"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E\u201026\/204.079\/2024"],"award-info":[{"award-number":["E\u201026\/204.079\/2024"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["88887.835146\/2023\u201000"],"award-info":[{"award-number":["88887.835146\/2023\u201000"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"abstract":"Abstract<\/jats:title>\n \n Aims<\/jats:title>\n \n Valproic acid<\/jats:ext-link>\n is an inhibitor of histone deacetylases (HDACs) and is used for the treatment of epileptic seizures. The drug (sodium valproate) has antihypertensive effects, and HDACs modulate renal Na\n +<\/jats:sup>\n \u2010transporting ATPases. The aim was to investigate whether valproate could be repositioned as an adjunctive drug for the prevention of acute kidney injury (AKI).\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n AKI due to ischemia followed by reperfusion (I\/R) was induced by clamping of the renal arteries in rats that had received valproate or a vehicle for 20\u2009days. Plasma creatinine and urea concentrations, and glomerular filtration rate (colorimetrically); plasma and urinary Na\n +<\/jats:sup>\n and K\n +<\/jats:sup>\n concentrations, and urinary excretion of Na\n +<\/jats:sup>\n and K\n +<\/jats:sup>\n (spectrophotometrically); proximal tubules (Na\n +<\/jats:sup>\n +K\n +<\/jats:sup>\n )ATPase activity (release of P\n i<\/jats:sub>\n from ATP); and blood pressure (pletismography) were measured 48\u2009h later.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n AKI increases plasma creatinine and returns to baseline values observed in non\u2010operated animals when I\/R rats are pretreated with valproate. Its decrease in urine is significantly prevented by valproate administration. The elevated plasma urea concentration is significantly reduced. Urinary excretion of Na\n +<\/jats:sup>\n and K\n +<\/jats:sup>\n decreases in I\/R, but while the former is recovered by valproate, this does not occur with K\n +<\/jats:sup>\n . The plasma levels of both ions remain ~10% below those of Sham controls. The decrease in (Na\n +<\/jats:sup>\n +K\n +<\/jats:sup>\n )ATPase activity in I\/R rats is totally prevented by valproate. The AKI\u2010provoked hypertension is prevented by valproate.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Valproate has pharmacological properties that point to its potential repositioning as an adjuvant in improving several outcomes in AKI and potentially avoiding progression to chronic kidney disease.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/bcp.70456","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T05:25:40Z","timestamp":1769491540000},"source":"Crossref","is-referenced-by-count":0,"title":["Possible therapeutic repositioning of valproic acid: From epileptic seizures to acute kidney injury"],"prefix":"10.1002","author":[{"given":"Danilo","family":"Alves\u2010Bezerra","sequence":"first","affiliation":[{"name":"Graduate Program in Translational Biomedicine\/BIOTRANS UNIGRANRIO University Duque de Caxias Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luiza B.","family":"Negreiros","sequence":"additional","affiliation":[{"name":"Graduate Program in Translational Biomedicine\/BIOTRANS UNIGRANRIO University Duque de Caxias Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amaury","family":"Pereira\u2010Ac\u00e1cio","sequence":"additional","affiliation":[{"name":"Graduate Program in Translational Biomedicine\/BIOTRANS UNIGRANRIO University Duque de Caxias Brazil"},{"name":"Carlos Chagas Filho Institute of Biophysics Federal University of Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isadora G.","family":"Almeida","sequence":"additional","affiliation":[{"name":"Department of Biophysics Federal University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o P. M.","family":"Veloso\u2010Santos","sequence":"additional","affiliation":[{"name":"Leopoldo de Meis Institute of Medical Biochemistry Federal University of Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3194-2845","authenticated-orcid":false,"given":"Jarlene A.","family":"Lopes","sequence":"additional","affiliation":[{"name":"Carlos Chagas Filho Institute of Biophysics Federal University of Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gl\u00f3ria","family":"Costa\u2010Sarmento","sequence":"additional","affiliation":[{"name":"Carlos Chagas Filho Institute of Biophysics Federal University of Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9183-1699","authenticated-orcid":false,"given":"Humberto","family":"Muzi\u2010Filho","sequence":"additional","affiliation":[{"name":"Carlos Chagas Filho Institute of Biophysics Federal University of Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8009-7273","authenticated-orcid":false,"given":"Adalberto","family":"Vieyra","sequence":"additional","affiliation":[{"name":"Graduate Program in Translational Biomedicine\/BIOTRANS UNIGRANRIO University Duque de Caxias Brazil"},{"name":"Carlos Chagas Filho Institute of Biophysics Federal University of Rio de Janeiro Rio de Janeiro Brazil"},{"name":"National Center for Structural Biology and Bioimaging\/CENABIO Federal University of Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.2"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000339789"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2020.01.005"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.34067\/KID.0000000000000466"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a018713"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2013.05.013"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20240291"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.120.16692"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277\u2010004\u20100850\u20102"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.110.154567"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5001988"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2012.11.008"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ame2.12035"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00587893"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021\u20109258(18)66180\u20100"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.30.4.809"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.33594\/000000306"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.946192"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20133219"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1546950"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1159\/000490007"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23062906"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4360"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00360\u2010018\u20101164\u20103"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c110041"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00456.2012"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13479"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12882\u2010025\u201004077\u20104"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104613\u20101473\u20108_49"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.367"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mnh.0000441151.55320.c3"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.02.034"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.145470"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1468"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.13273"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874467210902010095"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70456","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bcp.70456","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70456","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T05:25:42Z","timestamp":1769491542000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/bcp.70456"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,26]]},"references-count":37,"alternative-id":["10.1002\/bcp.70456"],"URL":"https:\/\/doi.org\/10.1002\/bcp.70456","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,26]]},"article-number":"bcp.70456"}}