{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T15:07:30Z","timestamp":1788793650231,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2021-NR065101"],"award-info":[{"award-number":["RS-2021-NR065101"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RS-2021-NR065101"],"award-info":[{"award-number":["RS-2021-NR065101"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background\/Objectives: Polydeoxyribonucleotide (PDRN) has anti-inflammatory and tissue-protective properties associated with activation of the adenosine A2A receptor (A2AR). Although hepatoprotective actions of PDRN have previously been described, its potential association with high-mobility group box 1 (HMGB1)-related inflammatory responses and hepatic macrophage accumulation during acute liver injury (ALI) is not fully understood. This study examined whether PDRN affects HMGB1- and monocyte chemoattractant protein-1 (MCP-1)-associated responses together with hepatic macrophage accumulation in ALI. Methods: ALI was induced in ICR mice by carbon tetrachloride (CCl4) administration. PDRN was administered either alone or together with the selective A2AR antagonist 3,7-dimethyl-1-propargylxanthine (DMPX). Serum levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase were quantified. Histological alterations were evaluated using hematoxylin and eosin staining. Hepatic macrophage accumulation was assessed by F4\/80 immunofluorescence staining. Enzyme-linked immunosorbent assays were used to quantify HMGB1, MCP-1, interleukin-10 (IL-10), cyclic adenosine monophosphate (cAMP), and A2AR. Results: PDRN significantly reduced serum markers of liver injury and attenuated histopathological damage following CCl4 administration. PDRN treatment also decreased F4\/80-positive macrophage accumulation in the hepatic tissue. In addition, PDRN reduced HMGB1 and MCP-1 levels in both the serum and liver tissues while significantly increasing IL-10, cAMP, and A2AR levels. Conclusions: PDRN attenuated CCl4-induced ALI and was associated with reduced HMGB1 and MCP-1 levels, decreased hepatic macrophage accumulation, and increased A2AR\/cAMP signaling. These findings suggest that modulation of macrophage-associated inflammatory responses may contribute to the hepatoprotective effects of PDRN.<\/jats:p>","DOI":"10.3390\/life16091498","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:53:28Z","timestamp":1788789208000},"page":"1498","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Polydeoxyribonucleotide Attenuates Carbon Tetrachloride-Induced Acute Liver Injury Through A2A Receptor-Related Anti-Inflammatory Responses"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2696-6869","authenticated-orcid":false,"given":"Il-Gyu","family":"Ko","sequence":"first","affiliation":[{"name":"Research Support Center, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4638-413X","authenticated-orcid":false,"given":"Su Bee","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul 05278, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9350-1079","authenticated-orcid":false,"given":"Hyun Phil","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul 05278, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Won","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul 05278, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5516-0947","authenticated-orcid":false,"given":"SeungHwan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul 05278, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1056\/NEJMra1208937","article-title":"Acute liver failure","volume":"369","author":"Bernal","year":"2013","journal-title":"N. 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