{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T17:38:43Z","timestamp":1784914723623,"version":"3.55.0"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["5\/9\/1328\/2020-Nut"],"award-info":[{"award-number":["5\/9\/1328\/2020-Nut"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019904","name":"Vellore Institute of Technology, Chennai","doi-asserted-by":"publisher","award":["RGEMS SG20250066"],"award-info":[{"award-number":["RGEMS SG20250066"]}],"id":[{"id":"10.13039\/100019904","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alcohol use disorder(AUD) is a chronic condition responsible for more than 3 million deaths annually worldwide and contributes to the development of multiple systemic comorbidities. Chronic alcohol consumption promotes inflammatory responses, immune suppression, antioxidant dysregulation, and nutritional deficiencies, severely affecting organs such as the liver and pancreas. Disruption of methionine metabolism and antioxidant defenses, including reduced availability of S-adenosyl-L-methionine (SAMe) and essential B-vitamins, has been implicated in alcohol-induced oxidative stress. Therefore, the aim of the present study was to investigate whether co-supplementation with SAMe and B-vitamins could alleviate ethanol-induced hepato-pancreatic injury by improving redox homeostasis and glutathione biosynthesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      C57BL\/6J male mice (n = 6 per group) were used to model acute-on-chronic alcohol-associated liver injury using the NIAAA chronic-plus-binge ethanol feeding model. From days 1\u201310, mice were fed a Lieber-DeCarli liquid diet containing 5% (v\/v) ethanol\n                      <jats:italic>(ad libitum)<\/jats:italic>\n                      to establish chronic ethanol exposure while receiving co-supplementation with SAMe(5\u00a0mg\/kg) and B-vitamins (B6-7\u00a0mg\/kg; B12-50\u00a0\u03bcg\/kg; B1-3.68\u00a0mg\/kg). On day 11, mice received a single ethanol dose of 5\u00a0g\/kg body weight by oral gavage as an acute binge ethanol exposure. Liver and pancreatic function was assessed by quantifying serum enzymatic markers. Oxidative and redox status was evaluated through biochemical estimation of nitric oxide, lipid peroxidation, hydrogen sulfide, and glutathione levels. Inflammatory responses were assessed by TNF-\u03b1 quantification and NF-\u03baB (p65) DNA-binding activity, while histopathological alterations were examined using H&amp;amp;E staining. Additionally, the expression of key genes (\n                      <jats:italic>Nos2, Gclc, Gpx1, and Cyp2e1<\/jats:italic>\n                      ) were analysed to corroborate the findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SAMe and B-vitamin co-supplementation significantly attenuated ethanol-induced hepato-pancreatic injury, evidenced by reduced activities of amylase, alanine aminotransferase, and aspartate aminotransferase, myeloperoxidase (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001) and promoted restoration of tissue architecture. Inflammatory signalling was markedly suppressed, reflected by decreased NF-\u03baB and TNF-\u03b1 levels (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05), alongside a significant reduction in oxidative stress markers, including nitric oxide, lipid peroxidation, and\n                      <jats:italic>Cyp2e1<\/jats:italic>\n                      expression (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001), collectively indicating a protective therapeutic effect.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Chronic ethanol exposure induces profound oxidative stress and impairs endogenous antioxidant defence system, culminating in severe hepato-pancreatic injury. Restoration of glutathione homeostasis and stabilization of cellular redox balance through SAMe and B-vitamins co-supplementation efficiently attenuated organ pathology, thereby improving the overall wellbeing of the affected individual.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1761748","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T04:36:28Z","timestamp":1776832588000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Restoring redox homeostasis through S-adenosyl-L-methionine and B-vitamins co-supplementation alleviates ethanol induced hepato-pancreatic injury by regulating glutathione biosynthesis in C57BL\/6J mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Prasanth Babu","family":"Nandagopal","sequence":"first","affiliation":[{"name":"School of Biosciences and Technology, Vellore Institute of Technology (VIT)","place":["Vellore, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkatraman","family":"Manickam","sequence":"additional","affiliation":[{"name":"School of Biosciences and Technology, Vellore Institute of Technology (VIT)","place":["Vellore, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e61122","DOI":"10.3791\/61122","article-title":"Evaluation of oxidative stress in biological samples using the thiobarbituric acid reactive substances assay","volume":"159","author":"Aguilar Diaz De Leon","year":"2020","journal-title":"J. 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