{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T05:25:07Z","timestamp":1783229107979,"version":"3.54.6"},"reference-count":31,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T00:00:00Z","timestamp":1690761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ayuda del Plan Regional de Investigaci\u00f3n de la Comunidad de Madrid","award":["08.1\/0013.1"],"award-info":[{"award-number":["08.1\/0013.1"]}]},{"name":"Ayuda del Plan Regional de Investigaci\u00f3n de la Comunidad de Madrid","award":["PR1\/03"],"award-info":[{"award-number":["PR1\/03"]}]},{"name":"Proyecto Investigaci\u00f3n Complutense","award":["08.1\/0013.1"],"award-info":[{"award-number":["08.1\/0013.1"]}]},{"name":"Proyecto Investigaci\u00f3n Complutense","award":["PR1\/03"],"award-info":[{"award-number":["PR1\/03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Hepatic ischemia\/reperfusion injury (IRI) can seriously impair liver function. It is initiated by oxidative stress, resulting in inflammation and apoptosis-induced cellular damage. Glutathione (GSH) prevents oxidative stress. S-Adenosylmethionine (SAMet) is a GSH synthesis precursor that avoids the deficit in SAMet-synthetase activity and contributes to intracellular ATP repletion. It also acts as a methyl group donor, stabilizing hepatocyte membranes, among other functions. This study investigated the effect of SAMet on bacterial translocation and levels of proinflammatory cytokines, oxidative stress and apoptosis markers in male Wistar rats subjected to hepatic IRI. Animals were randomly divided into six groups: (1) sham operation, (3) animals undergoing 60 min of ischemia of the right lateral lobe for temporary occlusion of the portal vein and hepatic artery plus 10 min of reperfusion, and (5) the same as (3) but with a reperfusion period of 120 min. Groups 2, 4 and 6, respectively, are the same as (1), (3) and (5), except that animals received SAMet (20 mg\/kg) 15 min before ischemia. GSH, ATP, lipid peroxidation (LPO), TNF-\u03b1, IL-1\u03b2, IL-6, total caspase-1 and caspase-9, total and cleaved caspase-3, and phosphatidylcholine were determined in the liver. Endotoxin, TNF-\u03b1, IL-1\u03b2, IL-6, IL-10 and LPO in vena cava and portal vein blood samples were also measured. Endotoxin and LPO levels as well as proinflammatory cytokines and apoptotic markers increased significantly in animals undergoing IRI, both after 10 and 120 min of reperfusion. IRI produced a significant decrease in GSH, ATP, portal IL-10 and phosphatidylcholine. SAMet treatment prevented these effects significantly and increased survival rate. The study suggests that SAMet exerts protective effects in hepatic IRI.<\/jats:p>","DOI":"10.3390\/antiox12081539","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T09:14:40Z","timestamp":1690881280000},"page":"1539","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["S-Adenosylmethionine Decreases Bacterial Translocation, Proinflammatory Cytokines, Oxidative Stress and Apoptosis Markers in Hepatic Ischemia-Reperfusion Injury in Wistar Rats"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0220-3384","authenticated-orcid":false,"given":"Sergio","family":"Vald\u00e9s","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Complutense University of Madrid, Avda. Complutense, s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4646-4199","authenticated-orcid":false,"given":"Sergio D.","family":"Paredes","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Complutense University of Madrid, Avda. Complutense, s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Garc\u00eda Carreras","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Complutense University of Madrid, Avda. Complutense, s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Zuluaga","sequence":"additional","affiliation":[{"name":"Departmental Unit of Biostatistics\u2014Department of Statistics and Operations Research, School of Medicine, Complutense University of Madrid, Avda. Complutense, s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1556-192X","authenticated-orcid":false,"given":"Lisa","family":"Rancan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Complutense University of Madrid, Avda. Complutense, s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0344-9877","authenticated-orcid":false,"given":"Beatriz","family":"Linillos-Pradillo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Complutense University of Madrid, Avda. Complutense, s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3002-3305","authenticated-orcid":false,"given":"Javier","family":"Arias-D\u00edaz","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine, Complutense University of Madrid, Avda. Complutense, s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5361-5215","authenticated-orcid":false,"given":"Elena","family":"Vara","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Complutense University of Madrid, Avda. Complutense, s\/n, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1159\/000489241","article-title":"Current Mechanistic Concepts in Ischemia and Reperfusion Injury","volume":"46","author":"Wu","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S31","DOI":"10.1002\/hep.21062","article-title":"Apoptosis and necrosis in the liver: A tale of two deaths?","volume":"43","author":"Malhi","year":"2006","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1097\/00003086-199701000-00005","article-title":"Assessment of ischemia-reperfusion injury","volume":"334","author":"Urbaniak","year":"1997","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_4","first-page":"e29696","article-title":"The Role of Glutathione Metabolism in Chronic Illness Development and Its Potential Use as a Novel Therapeutic Target","volume":"14","author":"Hristov","year":"2022","journal-title":"Cureus"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.tibs.2004.03.007","article-title":"S-adenosylmethionine: Nothing goes to waste","volume":"29","author":"Fontecave","year":"2004","journal-title":"Trends Biochem. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Pascale, R.M., Simile, M.M., Calvisi, D.F., Feo, C.F., and Feo, F. (2022). S-adenosylmethionine: From the discovery of its inhibition of tumorigenesis to its use as a therapeutic agent. Cells, 11.","DOI":"10.3390\/cells11030409"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1002\/hep.1840110203","article-title":"S-adenosyl-L-methionine attenuates alcohol-induced liver injury in the baboon","volume":"11","author":"Lieber","year":"1990","journal-title":"Hepatology"},{"key":"ref_8","first-page":"528","article-title":"Inhibition of glutathione synthesis in the liver leads to S-adenosyl-L-methionine synthetase reduction","volume":"14","author":"Corrales","year":"1991","journal-title":"Hepatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1248\/bpb.b15-00244","article-title":"Metabolism of Sulfur-Containing Amino Acids in the Liver: A Link between Hepatic Injury and Recovery","volume":"38","author":"Jung","year":"2015","journal-title":"Biol. Pharm. Bull."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/0022-4804(86)90119-8","article-title":"Hepatic ischemia models for determining the effects of ATP-MgCl2 treatment","volume":"40","author":"Hayashi","year":"1986","journal-title":"J. Surg. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1042\/bj0940705","article-title":"A colorimetric micro-method for the determination of glutathione","volume":"94","author":"Owens","year":"1965","journal-title":"Biochem. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"221","DOI":"10.7555\/JBR.32.20180087","article-title":"Hepatic ischemia-reperfusion injury in liver transplant setting: Mechanisms and protective strategies","volume":"33","author":"Rampes","year":"2019","journal-title":"J. Biomed. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1001\/jama.282.17.1659","article-title":"Alterations in Liver ATP Homeostasis in Human Nonalcoholic Steatohepatitis","volume":"282","author":"Chatham","year":"1999","journal-title":"JAMA"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Vairetti, M., Di Pasqua, L.G., Cagna, M., Richelmi, P., Ferrigno, A., and Berardo, C. (2021). Changes in Glutathione Content in Liver Diseases: An Update. Antioxidants, 10.","DOI":"10.3390\/antiox10030364"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5560","DOI":"10.1073\/pnas.091016398","article-title":"Methionine adenosyltransferase 1A knockout mice are predisposed to liver injury and exhibit increased expression of genes involved in proliferation","volume":"98","author":"Lu","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1097\/01.sla.0000110321.64275.95","article-title":"Glutathione Protects the Rat Liver Against Reperfusion Injury After Prolonged Warm Ischemia","volume":"239","author":"Schauer","year":"2004","journal-title":"Ann. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.molimm.2018.01.015","article-title":"S-Adenosylmethionine attenuates bile duct early warm ischemia reperfusion injury after rat liver transplantation","volume":"95","author":"Tang","year":"2018","journal-title":"Mol. Immunol."},{"key":"ref_18","unstructured":"Verlinden, W., Francque, S., and Vonghia, L. (2017). Biomarkers in Disease: Methods, Discoveries and Applications, Springer."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.cyto.2004.08.004","article-title":"Modulation of endotoxin stimulated interleukin-6 production in monocytes and Kupffer cells by S-adenosylmethionine (SAMe)","volume":"28","author":"Song","year":"2004","journal-title":"Cytokine"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kaltenmeier, C., Wang, R., Popp, B., Geller, D., Tohme, S., and Yazdani, H.O. (2022). Role of Immuno-Inflammatory Signals in Liver Ischemia-Reperfusion Injury. Cells, 11.","DOI":"10.3390\/cells11142222"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Norris, C.A., He, M., Kang, L.I., Ding, M.Q., Radder, J.E., Haynes, M.M., Yang, Y., Paranjpe, S., Bowen, W.C., and Orr, A. (2014). Synthesis of IL-6 by hepatocytes is a normal response to common hepatic stimuli. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096053"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1111\/j.1469-7793.2000.00653.x","article-title":"Circulating interleukin-6 mediates the febrile response to localised inflammation in rats","volume":"526","author":"Cartmell","year":"2000","journal-title":"J. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1056\/NEJMra2026131","article-title":"Cytokine Storm","volume":"383","author":"Fajgenbaum","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/j.molcel.2019.06.039","article-title":"One-Carbon Metabolism Supports S-Adenosylmethionine and Histone Methylation to Drive Inflammatory Macrophages","volume":"75","author":"Yu","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_25","first-page":"G471","article-title":"Quantifying oxidative injury in the liver","volume":"268","author":"Poggetti","year":"1995","journal-title":"Am. J. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3164\/jcbn.17-137","article-title":"Microbiome and intestinal ischemia\/reperfusion injury","volume":"63","author":"Nadatani","year":"2018","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_27","first-page":"G397","article-title":"Gut phospholipase A2 mediates neutrophil priming and lung injury after mesenteric ischemia-reperfusion","volume":"268","author":"Koike","year":"1995","journal-title":"Am. J. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1042\/bj2930143","article-title":"Rat liver mitochondrial phospholipase A2 is an endotoxin-stimulated membrane-associated enzyme of Kupffer cells which is released during liver perfusion","volume":"293","author":"Hatch","year":"1993","journal-title":"Biochem. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1186\/s12967-019-2052-7","article-title":"Modeling trauma in rats: Similarities to humans and potential pitfalls to consider","volume":"17","author":"Weber","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"G63","DOI":"10.1152\/ajpgi.00112.2013","article-title":"Animal models of ischemia-reperfusion-induced intestinal injury: Progress and promise for translational research","volume":"308","author":"Gonzalez","year":"2015","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.jss.2014.06.024","article-title":"Rodent models of hepatic ischemia-reperfusion injury: Time and percentage-related pathophysiological mechanisms","volume":"191","author":"Karatzas","year":"2014","journal-title":"J. Surg. Res."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/8\/1539\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:23:24Z","timestamp":1760127804000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/8\/1539"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,31]]},"references-count":31,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["antiox12081539"],"URL":"https:\/\/doi.org\/10.3390\/antiox12081539","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,31]]}}}