{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T05:00:41Z","timestamp":1775797241754,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"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","id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To evaluate the impact of multiple apical periodontitis (AP) on the expression of TLR4\/NF\u2010\u03baB pathway components, proinflammatory cytokine levels, and development of hepatic injuries in rats with and without chronic alcohol consumption.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>\n                      Thirty\u2010two rats were assigned to four groups (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20098): Control, AP, Alcohol, and Alcohol+AP. The Alcohol and Alcohol+AP groups received 25% ethanol solution. Multiple AP were induced through pulp exposure of four molars for 28\u2009days. Following euthanasia, the jaws and livers were collected. Micro\u2010computed tomography was used to confirm periapical lesions. Liver samples underwent histopathological analysis and ELISA assay to measure TLR4, NF\u2010\u03baB, IL\u20106, and TNF\u2010\u03b1 levels. Histopathological evaluation was performed using hepatic stereology to assess hepatocytes, sinusoids, Kupffer cells, steatosis, leukocyte infiltrate, and necrosis. Statistical analysis was carried out using one\u2010way ANOVA followed by the Student\u2013Newman\u2013Keuls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Hepatic levels of TLR4 and NF\u2010\u03baB were significantly higher in AP and Alcohol+AP groups compared to Control and Alcohol groups (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). IL\u20106 and TNF\u2010\u03b1 were significantly elevated in all experimental groups compared to the Control group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), with higher levels observed in the Alcohol+AP group compared to the other groups (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Experimental groups showed a significant reduction in hepatocyte density compared to the Control group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), while sinusoidal volume was significantly reduced in the AP group compared to the Control group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Hepatic steatosis was absent in the Control and AP groups and there was no significant difference in the percentage of steatosis between Alcohol and Alcohol+AP groups (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05). No significant differences were observed in the number of Kupffer cells among groups (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05) and leukocyte infiltrate was absent in all groups. Necrosis was significantly higher in the AP and Alcohol+AP groups compared to the Control and Alcohol groups (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), with the Alcohol+AP group showing a higher percentage of necrosis compared to the AP group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Hydropic degeneration, focal inflammatory infiltrates, and hepatocyte necrosis were observed in the AP and Alcohol+AP groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Multiple AP led to elevated TLR4, NF\u2010\u03baB, IL\u20106, and TNF\u2010\u03b1 levels and significant hepatic alterations including hepatocyte degeneration and necrosis. When combined with alcohol consumption, multiple AP exacerbated ethanol\u2010induced liver damage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iej.70104","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T04:15:29Z","timestamp":1769055329000},"page":"863-872","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multiple Periapical Lesions Influence the Expression of TLR4\/NF\u2010\u03baB Pathway Components and the Development of Hepatic Injuries in Healthy and Chronic Alcohol\u2010Consuming Rats"],"prefix":"10.1111","volume":"59","author":[{"given":"Karem Paula","family":"Pinto","sequence":"first","affiliation":[{"name":"Department of Integrated Clinical Procedures, School of Dentistry Rio de Janeiro State University (UERJ)  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"da Cunha Degani","sequence":"additional","affiliation":[{"name":"Department of Integrated Clinical Procedures, School of Dentistry Rio de Janeiro State University (UERJ)  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenif Braga","family":"de Souza","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Surgery, School of Medical Sciences Rio de Janeiro State University (UERJ)  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata Heisler","family":"Neves","sequence":"additional","affiliation":[{"name":"Romero Lascasas Porto Laboratory of Helminthology, Department of Microbiology, Immunology and Parasitology, Medical Sciences College (FCM) Rio de Janeiro State University (UERJ)  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciana","family":"Brand\u00e3o\u2010Bezerra","sequence":"additional","affiliation":[{"name":"Romero Lascasas Porto Laboratory of Helminthology, Department of Microbiology, Immunology and Parasitology, Medical Sciences College (FCM) Rio de Janeiro State University (UERJ)  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6181-7490","authenticated-orcid":false,"given":"Luciana Moura","family":"Sassone","sequence":"additional","affiliation":[{"name":"Department of Integrated Clinical Procedures, School of Dentistry Rio de Janeiro State University (UERJ)  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6445-8243","authenticated-orcid":false,"given":"Emmanuel Jo\u00e3o Nogueira Leal","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Integrated Clinical Procedures, School of Dentistry Rio de Janeiro State University (UERJ)  Rio de Janeiro Brazil"},{"name":"Departament of Endodontics Grande Rio University (UNIGRANRIO)  Rio de Janeiro 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