{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:40:04Z","timestamp":1760402404922,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T00:00:00Z","timestamp":1588118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003100","name":"F\u00e9d\u00e9ration Fran\u00e7aise de Cardiologie","doi-asserted-by":"publisher","award":["TL15"],"award-info":[{"award-number":["TL15"]}],"id":[{"id":"10.13039\/501100003100","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009597","name":"ADETEC","doi-asserted-by":"publisher","award":["ADETEC03"],"award-info":[{"award-number":["ADETEC03"]}],"id":[{"id":"10.13039\/501100009597","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>It has been proven that dietary eicosapentaenoic acid (C20:5 n-3 or EPA) protects the heart against the deleterious effects of sepsis in female rats. We do not know if this is the case for male rodents. In this case, the efficiency of other n-3 polyunsaturated fatty acids (PUFAs) remains to be determined in both female and male rats. This study aimed at (i) determining whether dietary EPA is cardioprotective in septic male rats; (ii) evaluating the influence of dietary \u03b1-linolenic (C18:3 n-3 or ALA) on cardiac function during this pathology; and (iii) finding out the physiological and molecular mechanisms responsible for the observed effects. Sixty male rats were divided into three dietary groups. The animals were fed a diet deficient in n-3 PUFAs (DEF group), a diet enriched with ALA (ALA group) or a diet fortified with EPA (EPA group) for 6 weeks. Thereafter, each group was subdivided into 2 subgroups, one being subjected to cecal ligation and puncture (CLP) and the other undergoing a fictive surgery. Cardiac function was determined in vivo and ex vivo. Several parameters related to the inflammation process and oxidative stress were determined. Finally, the fatty acid compositions of circulating lipids and cardiac phospholipids were evaluated. The results of the ex vivo situation indicated that sepsis triggered cardiac damage in the DEF group. Conversely, the ex vivo data indicated that dietary ALA and EPA were cardioprotective by resolving the inflammation process and decreasing the oxidative stress. However, the measurements of the cardiac function in the in vivo situation modulated these conclusions. Indeed, in the in vivo situation, sepsis deteriorated cardiac mechanical activity in the ALA group. This was suspected to be due to a restricted coronary flow which was related to a lack of cyclooxygenase substrates in membrane phospholipids. Finally, only EPA proved to be beneficial in sepsis. Its action necessitates both resolution of inflammation and increased coronary perfusion. In that sense, dietary ALA, which does not allow the accumulation of vasodilator precursors in membrane lipids, cannot be protective during the pathology.<\/jats:p>","DOI":"10.3390\/antiox9050371","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T13:23:45Z","timestamp":1588166625000},"page":"371","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["EPA Is Cardioprotective in Male Rats Subjected to Sepsis, but ALA is Not Beneficial"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0330-7203","authenticated-orcid":false,"given":"Thibault","family":"Leger","sequence":"first","affiliation":[{"name":"UNH, Unit\u00e9 de Nutrition Humaine, UMR 1019, Universit\u00e9 Clermont Auvergne, INRAE, CRNH Auvergne, 63000 Clermont-Ferrand, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chryst\u00e8le","family":"Jouve","sequence":"additional","affiliation":[{"name":"UNH, Unit\u00e9 de Nutrition Humaine, UMR 1019, Universit\u00e9 Clermont Auvergne, INRAE, CRNH Auvergne, 63000 Clermont-Ferrand, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6726-7533","authenticated-orcid":false,"given":"Isabelle","family":"Hininger-Favier","sequence":"additional","affiliation":[{"name":"LBFA U1055, Universit\u00e9 Grenoble Alpes, INSERM, 38058 Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3439-0663","authenticated-orcid":false,"given":"Jean-Paul","family":"Rigaudiere","sequence":"additional","affiliation":[{"name":"UNH, Unit\u00e9 de Nutrition Humaine, UMR 1019, Universit\u00e9 Clermont Auvergne, INRAE, CRNH Auvergne, 63000 Clermont-Ferrand, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0133-0277","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Capel","sequence":"additional","affiliation":[{"name":"UNH, Unit\u00e9 de Nutrition Humaine, UMR 1019, Universit\u00e9 Clermont Auvergne, INRAE, CRNH Auvergne, 63000 Clermont-Ferrand, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7452-315X","authenticated-orcid":false,"given":"Vincent","family":"Sapin","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Molecular Biology, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clarisse","family":"Moreau","sequence":"additional","affiliation":[{"name":"UNH, Unit\u00e9 de Nutrition Humaine, UMR 1019, Universit\u00e9 Clermont Auvergne, INRAE, CRNH Auvergne, 63000 Clermont-Ferrand, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Charrier","sequence":"additional","affiliation":[{"name":"UNH, Unit\u00e9 de Nutrition Humaine, UMR 1019, Universit\u00e9 Clermont Auvergne, INRAE, CRNH Auvergne, 63000 Clermont-Ferrand, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0771-7250","authenticated-orcid":false,"given":"Luc","family":"Demaison","sequence":"additional","affiliation":[{"name":"UNH, Unit\u00e9 de Nutrition Humaine, UMR 1019, Universit\u00e9 Clermont Auvergne, INRAE, CRNH Auvergne, 63000 Clermont-Ferrand, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.4161\/viru.27372","article-title":"Epidemiology of severe sepsis","volume":"5","author":"Mayr","year":"2014","journal-title":"Virulence"},{"key":"ref_2","unstructured":"Torio, C.M., and Moore, B.J. (2006). National inpatient hospital costs: The most expensive conditions by payer, 2013: Statistical Brief #204. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs, Agency for Healthcare Research and Quality (US)."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.1182\/blood.V96.7.2584","article-title":"Comprehensive gene expression profile of LPS-stimulated human monocytes by SAGE","volume":"96","author":"Suzuki","year":"2000","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1093\/bja\/aev349","article-title":"A rational approach to fluid therapy in sepsis","volume":"116","author":"Marik","year":"2016","journal-title":"Br. J. Anaesth."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1590\/S1679-45082015RW3273","article-title":"Fluid therapy for septic shock resuscitation: Which fluid should be used?","volume":"13","author":"Rocha","year":"2015","journal-title":"Einstein (Sao Paulo)"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"R158","DOI":"10.1186\/cc7157","article-title":"Incidence, organ dysfunction and mortality in severe sepsis: A Spanish multicentre study","volume":"12","author":"Blanco","year":"2008","journal-title":"Crit. Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1007\/s001340051030","article-title":"Cardiac troponin: A new serum marker of myocardial injury in sepsis","volume":"25","author":"Fernandes","year":"1999","journal-title":"Intensive Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1159\/000315915","article-title":"Endotoxins and other sepsis triggers","volume":"167","author":"Opal","year":"2010","journal-title":"Contrib. Nephrol."},{"key":"ref_9","first-page":"9","article-title":"Endotoxin-Induced IL-6 Promoter Activation in Skeletal Muscle Requires an NF-kappaB Site","volume":"2010","author":"Yeagley","year":"2010","journal-title":"Int. J. Interferon Cytokine Mediat. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1093\/eurheartj\/ehq484","article-title":"When are pro-inflammatory cytokines SAFE in heart failure?","volume":"32","author":"Lecour","year":"2011","journal-title":"Eur. Heart J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.2174\/092986707781368405","article-title":"Anti-arrhythmic properties of n-3 polyunsaturated fatty acids (n-3 PUFA)","volume":"14","author":"Lombardi","year":"2007","journal-title":"Curr. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0925-4439(94)90106-6","article-title":"Influence of the phospholipid n-6\/n-3 polyunsaturated fatty acid ratio on the mitochondrial oxidative metabolism before and after myocardial ischemia","volume":"1227","author":"Demaison","year":"1994","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1017\/S0007114511005915","article-title":"Dietary fish oil preserves cardiac function in the hypertrophied rat heart","volume":"108","author":"McLennan","year":"2012","journal-title":"Br. J. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S83","DOI":"10.1007\/s11745-001-0687-7","article-title":"n-3 fatty acids and human health: Defining strategies for public policy","volume":"36","author":"Simopoulos","year":"2001","journal-title":"Lipids"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1183\/09031936.00005807","article-title":"Endogenous lipid mediators in the resolution of airway inflammation","volume":"30","author":"Haworth","year":"2007","journal-title":"Eur. Respir. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1089\/ars.2009.2930","article-title":"Targeting the vicious inflammation-oxidative stress cycle for the management of heart failure","volume":"13","author":"Khaper","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"836","DOI":"10.4049\/jimmunol.0901809","article-title":"The anti-inflammatory and proresolving mediator resolvin E1 protects mice from bacterial pneumonia and acute lung injury","volume":"184","author":"Seki","year":"2010","journal-title":"J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.surneu.2005.10.023","article-title":"Omega-3 fatty acids (fish oil) as an anti-inflammatory: An alternative to nonsteroidal anti-inflammatory drugs for discogenic pain","volume":"65","author":"Maroon","year":"2006","journal-title":"Surg. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9710352","DOI":"10.1155\/2019\/9710352","article-title":"Antioxidant and cardioprotective effects of EPA on early low-severity sepsis through UCP3 and SIRT3 upholding of the mitochondrial redox potential","volume":"2019","author":"Leger","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s12986-018-0252-4","article-title":"Dietary canolol protects the heart against the deleterious effects induced by the association of rapeseed oil, vitamin E and coenzyme Q10 in the context of a high-fat diet","volume":"15","author":"Capel","year":"2018","journal-title":"Nutr. Metab. (Lond)"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Limbu, R., Cottrell, G.S., and McNeish, A.J. (2018). Characterisation of the vasodilation effects of DHA and EPA, n-3 PUFAs (fish oils), in rat aorta and mesenteric resistance arteries. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192484"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"15184","DOI":"10.1073\/pnas.0510086103","article-title":"The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKC epsilon inhibition","volume":"103","author":"Massaro","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","first-page":"e2860","article-title":"Cecal ligation puncture procedure","volume":"51","author":"Toscano","year":"2011","journal-title":"J. Vis. Exp."},{"key":"ref_24","unstructured":"Bergmeyer, H.U. (1974). Methods of Enzymatic Analysis, Academic Press."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Favier, A.E., Cadet, J., Kalyanamaran, B., Fontecave, M., and Pierre, J.L. (1995). Measurement of plasma sulfhydryl and carbonyl groups as a possible indicator of protein oxidation. Analysis of Free Radicals in Biological Systems, Birkh\u00e4user.","DOI":"10.1007\/978-3-0348-9074-8"},{"key":"ref_26","first-page":"444","article-title":"An improved coupled test procedure for glutathione peroxidase (EC-1-11-1-9-) in blood","volume":"12","author":"Kremers","year":"1974","journal-title":"Z. Clin. Chem. Klin. Biochem."},{"key":"ref_27","unstructured":"Feingold, K.R., Anawalt, B., Boyce, A., Chrousos, G., Dungan, K., Grossman, A., Hershman, J.M., Kaltsas, G., Koch, C., and Kopp, P. (2019, January 08). The effect of inflammation and infection on lipids and lipoproteins, Endotext, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/26561701\/."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s11745-016-4226-x","article-title":"Plasma phospholipid fatty acid profile is altered in both septic and non-septic critically ill: A correlation with inflammatory markers and albumin","volume":"52","author":"Novak","year":"2017","journal-title":"Lipids"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1136\/bmjspcare-2017-001440","article-title":"Cancer cachexia: Rationale for the MENAC (Multimodal-Exercise, Nutrition and Anti-inflammatory medication for Cachexia) trial","volume":"8","author":"Solheim","year":"2018","journal-title":"BMJ Support. Palliat. Care"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.bbabio.2004.03.016","article-title":"Inhibition of mitochondrial respiratory complex I by nitric oxide, peroxynitrite and S-nitrosothiols","volume":"1658","author":"Brown","year":"2004","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"13344","DOI":"10.1038\/ncomms13344","article-title":"Macrophage-dependent IL-1beta production induces cardiac arrhythmias in diabetic mice","volume":"7","author":"Monnerat","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1096\/fj.03-0159hyp","article-title":"A function for novel uncoupling proteins: Antioxidant defense of mitochondrial matrix by translocating fatty acid peroxides from the inner to the outer membrane leaflet","volume":"17","author":"Goglia","year":"2003","journal-title":"FASEB J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1042\/BJ20112019","article-title":"Interleukin-6 counteracts therapy-induced cellular oxidative stress in multiple myeloma by up-regulating manganese superoxide dismutase","volume":"444","author":"Brown","year":"2012","journal-title":"Biochem. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3574","DOI":"10.1161\/STROKEAHA.111.626648","article-title":"Neuroprotection by interleukin-6 is mediated by signal transducer and activator of transcription 3 and antioxidative signaling in ischemic stroke","volume":"42","author":"Jung","year":"2011","journal-title":"Stroke"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.ejcb.2014.05.004","article-title":"Regulation of SOD2 and beta-arrestin1 by interleukin-6 contributes to the increase of IGF-1R expression in docetaxel resistant prostate cancer cells","volume":"93","author":"Zhang","year":"2014","journal-title":"Eur. J. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/978-1-61779-382-0_12","article-title":"Relation between mitochondrial membrane potential and ROS formation","volume":"810","author":"Suski","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.biochi.2003.08.006","article-title":"Cell death and inflammation during infection with the obligate intracellular pathogen, Chlamydia","volume":"85","author":"Perfettini","year":"2003","journal-title":"Biochimie"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/9\/5\/371\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:32:17Z","timestamp":1760362337000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/9\/5\/371"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,29]]},"references-count":37,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["antiox9050371"],"URL":"https:\/\/doi.org\/10.3390\/antiox9050371","relation":{},"ISSN":["2076-3921"],"issn-type":[{"type":"electronic","value":"2076-3921"}],"subject":[],"published":{"date-parts":[[2020,4,29]]}}}