{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T20:07:09Z","timestamp":1793650029061,"version":"4.5.1"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Suleyman Demirel University"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Apoptosis"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Acute lung injury secondary to sepsis remains a major problem in critical patients. Lipopolysaccharide (LPS)-induced lung injury is characterized by inflammatory infiltration, oxidative stress, and extensive apoptosis, particularly via the mitochondrial pathway. Omega-3 (OM3) polyunsaturated fatty acids have been proposed as promising modulators of inflammation and oxidative damage. However, their role in regulating mitochondria-mediated apoptosis in sepsis remains underexplored. Thirty-two female Wistar albino rats were randomized into four groups: Control, LPS (5\u00a0mg\/kg, i.p. 3th), LPS-OM3 (400\u00a0mg\/kg\/day, i.p., 3\u00a0day), and OM3 only. After 72\u00a0h, lung tissues were collected for histopathological scoring, immunohistochemistry as tumor necrosis factor-alpha (TNF-\u03b1), heat shock protein (HSP70), caspase-3 (Cas-3); biochemical analyses as total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and qRT-PCR for mitochondrial apoptosis markers B cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), cytochrome-c (Cyt-c) and Cas-9. LPS induced ALI characterized by bronchiolar epithelial degeneration, alveolar hemorrhage, inflammation, and hyaline membrane formation. Biochemically, TOS and OSI levels were significantly elevated, while TAS remained unchanged. Immunohistochemical and genetic analysis showed marked upregulation of TNF-\u03b1, HSP70, and Cas-3 Bax, Cyt-c, and Casp-9 expression and decreased Bcl-2 expression in the LPS group. OM3 supplementation significantly attenuated histopathological damage, reduced oxidative stress markers, suppressed immunopositivity of proinflammatory and apoptotic proteins, and favorably modulated the apoptosis-related gene expressions. OM3 fatty acids exert a potent protective effect against LPS-induced ALI by suppressing mitochondrial apoptosis, reducing oxidative stress, and modulating the inflammatory response. These findings highlight the therapeutic potential of OM3 in mitigating sepsis-associated pulmonary damage through mitochondrial preservation.<\/jats:p>","DOI":"10.1007\/s10495-026-02325-y","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T07:38:42Z","timestamp":1774597122000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeting mitochondrial apoptosis in septic lung injury: protective potential of omega-3 fatty acids"],"prefix":"10.1007","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2002-8627","authenticated-orcid":false,"given":"Ersin","family":"\u00c7elik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6210-5962","authenticated-orcid":false,"given":"P\u0131nar","family":"Karabacak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0385-2308","authenticated-orcid":false,"given":"Mustafa Soner","family":"\u00d6zcan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3739-9580","authenticated-orcid":false,"given":"\u0130lter","family":"\u0130lhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1087-4874","authenticated-orcid":false,"given":"Muhammet Yusuf","family":"Tepeba\u015f\u0131","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4671-9315","authenticated-orcid":false,"given":"Emine","family":"Sarman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4356-5857","authenticated-orcid":false,"given":"Melih","family":"Arl\u0131o\u011flu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1545-035X","authenticated-orcid":false,"given":"Halil","family":"A\u015fc\u0131","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"issue":"9","key":"2325_CR1","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1016\/j.biocel.2012.06.003","volume":"44","author":"KH Al-Gubory","year":"2012","unstructured":"Al-Gubory KH (2012) Mitochondria: omega-3 in the route of mitochondrial reactive oxygen species. Int J Biochem Cell Biol 44(9):1569\u20131573. https:\/\/doi.org\/10.1016\/j.biocel.2012.06.003","journal-title":"Int J Biochem Cell Biol"},{"issue":"2","key":"2325_CR2","doi-asserted-by":"publisher","first-page":"274","DOI":"10.3390\/IJERPH16020274","volume":"16","author":"M Andjelkovic","year":"2019","unstructured":"Andjelkovic M, Djordjevic AB, Antonijevic E, Antonijevic B, Stanic M, Kotur-Stevuljevic J, Spasojevic-Kalimanovska V, Jovanovic M, Boricic N, Wallace D, Bulat Z (2019) Toxic effect of acute Cadmium and Lead exposure in rat blood, liver, and kidney. Int J Environ Res Public Health 16(2):274. https:\/\/doi.org\/10.3390\/IJERPH16020274","journal-title":"Int J Environ Res Public Health"},{"issue":"8","key":"2325_CR3","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1038\/35019501","volume":"2","author":"HM Beere","year":"2000","unstructured":"Beere HM, Wolf BB, Cain K, Mosser DD, Mahboubi A, Kuwana T, Tailor P, Morimoto RI, Cohen GM, Green DR (2000) Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol 2(8):469\u2013475. https:\/\/doi.org\/10.1038\/35019501","journal-title":"Nat Cell Biol"},{"issue":"1","key":"2325_CR4","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1136\/BMJNPH-2020-000085","volume":"3","author":"PC Calder","year":"2020","unstructured":"Calder PC (2020) Nutrition, immunity and COVID-19. BMJ Nutr Prev Health 3(1):74\u201392. https:\/\/doi.org\/10.1136\/BMJNPH-2020-000085","journal-title":"BMJ Nutr Prev Health"},{"key":"2325_CR5","doi-asserted-by":"publisher","DOI":"10.3390\/MD16110453","author":"CM Champigny","year":"2018","unstructured":"Champigny CM, Cormier RPJ, Simard CJ, St-Coeur PD, Fortin S, Pichaud N (2018) Omega-3 monoacylglyceride effects on longevity, mitochondrial metabolism and oxidative stress: insights from Drosophila melanogaster. Mar Drugs. https:\/\/doi.org\/10.3390\/MD16110453","journal-title":"Mar Drugs"},{"key":"2325_CR6","doi-asserted-by":"publisher","DOI":"10.1186\/S12937-018-0356-8","author":"H Chen","year":"2018","unstructured":"Chen H, Wang S, Zhao Y, Luo Y, Tong H, Su L (2018) Correlation analysis of omega-3 fatty acids and mortality of sepsis and sepsis-induced ARDS in adults: data from previous randomized controlled trials. Nutr J. https:\/\/doi.org\/10.1186\/S12937-018-0356-8","journal-title":"Nutr J"},{"key":"2325_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2022.111886","author":"ZS Chen","year":"2023","unstructured":"Chen ZS, Yu MM, Wang K, Meng XL, Liu YC, Shou ST, Chai YF (2023) Omega-3 polyunsaturated fatty acids inhibit cardiomyocyte apoptosis and attenuate sepsis-induced cardiomyopathy. Nutrition. https:\/\/doi.org\/10.1016\/j.nut.2022.111886","journal-title":"Nutrition"},{"issue":"4","key":"2325_CR8","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1007\/S10753-013-9622-2","volume":"36","author":"D Coquerel","year":"2013","unstructured":"Coquerel D, Ku\u0161\u00edkov\u00e1 E, Mulder P, Co\u00ebffier M, Renet S, Dechelotte P, Richard V, Thuillez C, Tamion F (2013) Omega-3 polyunsaturated fatty acids delay the progression of endotoxic shock-induced myocardial dysfunction. Inflammation 36(4):932\u2013940. https:\/\/doi.org\/10.1007\/S10753-013-9622-2","journal-title":"Inflammation"},{"issue":"6","key":"2325_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/NU12061742","volume":"12","author":"CY Huang","year":"2020","unstructured":"Huang CY, Deng JS, Huang WC, Jiang WP, Huang GJ (2020) Attenuation of lipopolysaccharide-induced acute lung injury by hispolon in mice, through regulating the TLR4\/PI3K\/Akt\/mTOR and Keap1\/Nrf2\/HO-1 pathways, and suppressing oxidative stress-mediated ER stress-induced apoptosis and autophagy. Nutrients 12(6):1\u201322. https:\/\/doi.org\/10.3390\/NU12061742","journal-title":"Nutrients"},{"key":"2325_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2021.108901","author":"M Kalogerou","year":"2022","unstructured":"Kalogerou M, Ioannou S, Kolovos P, Prokopiou E, Potamiti L, Kyriacou K, Panagiotidis M, Ioannou M, Fella E, Worth EP, Georgiou T (2022) Omega-3 fatty acids promote neuroprotection, decreased apoptosis and reduced glial cell activation in the retina of a mouse model of OPA1-related autosomal dominant optic atrophy. Exp Eye Res. https:\/\/doi.org\/10.1016\/j.exer.2021.108901","journal-title":"Exp Eye Res"},{"key":"2325_CR11","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2022.102426","author":"C Kocherlakota","year":"2022","unstructured":"Kocherlakota C, Nagaraju B, Arjun N, Srinath A, Kothapalli KSD, Brenna JT (2022) Inhalation of nebulized omega-3 fatty acids mitigate LPS-induced acute lung inflammation in rats: implications for treatment of COPD and COVID-19. Prostaglandins Leukot Essent Fatty Acids. https:\/\/doi.org\/10.1016\/j.plefa.2022.102426","journal-title":"Prostaglandins Leukot Essent Fatty Acids"},{"key":"2325_CR12","doi-asserted-by":"publisher","DOI":"10.1186\/S12967-024-05906-0","author":"W Li","year":"2025","unstructured":"Li W, Li Y, Xiao L, Xie Z, Peng J, Huang W, Li X, Meng Y (2025) Micheliolide attenuates sepsis-induced acute lung injury by suppressing mitochondrial oxidative stress and PFKFB3-driven glycolysis. J Transl Med. https:\/\/doi.org\/10.1186\/S12967-024-05906-0","journal-title":"J Transl Med"},{"key":"2325_CR13","doi-asserted-by":"publisher","DOI":"10.1016\/J.BIOPHA.2019.109363","author":"X Li","year":"2019","unstructured":"Li X, Jamal M, Guo P, Jin Z, Zheng F, Song X, Zhan J, Wu H (2019) Irisin alleviates pulmonary epithelial barrier dysfunction in sepsis-induced acute lung injury via activation of AMPK\/SIRT1 pathways. Biomed Pharmacother. https:\/\/doi.org\/10.1016\/J.BIOPHA.2019.109363","journal-title":"Biomed Pharmacother"},{"issue":"4","key":"2325_CR14","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2-\u0394\u0394CT method. Methods 25(4):402\u2013408. https:\/\/doi.org\/10.1006\/meth.2001.1262","journal-title":"Methods"},{"key":"2325_CR15","doi-asserted-by":"publisher","DOI":"10.1038\/S41572-019-0069-0","author":"MA Matthay","year":"2018","unstructured":"Matthay MA, Zemans RL, Zimmerman GA, Arabi YM, Beitler JR, Mercat A, Herridge M, Randolph AG, Calfee CS (2018) Acute respiratory distress syndrome. Nat Rev Dis Prim. https:\/\/doi.org\/10.1038\/S41572-019-0069-0","journal-title":"Nat Rev Dis Prim"},{"key":"2325_CR16","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/5987082","author":"A Molfino","year":"2017","unstructured":"Molfino A, Amabile MI, Monti M, Muscaritoli M (2017) Omega-3 polyunsaturated fatty acids in critical illness: Anti-inflammatory, proresolving, or both? Oxid Med Cell Longev. https:\/\/doi.org\/10.1155\/2017\/5987082","journal-title":"Oxid Med Cell Longev"},{"issue":"5","key":"2325_CR17","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1080\/08923973.2024.2384904","volume":"46","author":"O Ozmen","year":"2024","unstructured":"Ozmen O, Asci H, Uysal D, Ilhan I, Taner R, Arl\u0131oglu M, Milletsever A, Tasan S (2024) The prophylactic and therapeutic effects of cannabidiol on lung injury secondary to cardiac ischemia model in rats via PERK\/NRF2\/CHOP\/BCL2 pathway. Immunopharmacol Immunotoxicol 46(5):594\u2013603. https:\/\/doi.org\/10.1080\/08923973.2024.2384904","journal-title":"Immunopharmacol Immunotoxicol"},{"key":"2325_CR18","doi-asserted-by":"publisher","DOI":"10.1007\/S11033-025-10267-Y","author":"M Savran","year":"2025","unstructured":"Savran M, Akin SE, Camas HE, Ilhan I, Arlioglu M, Zeynalov T, Ozmen O, Ozcan MS (2025) Protective effect of dapagliflozin on lipopolysaccharide-induced acute lung injury via the SIRT-1\/PGC-1\u03b1 pathway. Mol Biol Rep. https:\/\/doi.org\/10.1007\/S11033-025-10267-Y","journal-title":"Mol Biol Rep"},{"key":"2325_CR19","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1146\/ANNUREV-FOOD-111317-095850","volume":"9","author":"F Shahidi","year":"2018","unstructured":"Shahidi F, Ambigaipalan P (2018) Omega-3 polyunsaturated fatty acids and their health benefits. Annu Rev Food Sci Technol 9:345\u2013381. https:\/\/doi.org\/10.1146\/ANNUREV-FOOD-111317-095850","journal-title":"Annu Rev Food Sci Technol"},{"key":"2325_CR20","doi-asserted-by":"publisher","DOI":"10.3390\/JCM12010304","author":"F Velotti","year":"2023","unstructured":"Velotti F, Costantini L, Merendino N (2023) Omega-3 polyunsaturated fatty acids (n-3 PUFAs) for \u0131mmunomodulation in COVID-19 related acute respiratory distress syndrome (ARDS). J Clin Med. https:\/\/doi.org\/10.3390\/JCM12010304","journal-title":"J Clin Med"},{"issue":"6","key":"2325_CR21","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/NRI2975","volume":"11","author":"AP West","year":"2011","unstructured":"West AP, Shadel GS, Ghosh S (2011) Mitochondria in innate immune responses. Nat Rev Immunol 11(6):389\u2013402. https:\/\/doi.org\/10.1038\/NRI2975","journal-title":"Nat Rev Immunol"},{"issue":"2","key":"2325_CR22","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.bbrc.2015.02.103","volume":"459","author":"S Wu","year":"2015","unstructured":"Wu S, Guo Y, Wu Y, Zhu S, He Z, Chen YQ (2015) Omega-3 free fatty acids inhibit tamoxifen-induced cell apoptosis. Biochem Biophys Res Commun 459(2):294\u2013299. https:\/\/doi.org\/10.1016\/j.bbrc.2015.02.103","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"2325_CR23","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/NRM2308","volume":"9","author":"RJ Youle","year":"2008","unstructured":"Youle RJ, Strasser A (2008) The BCL-2 protein family: Opposing activities that mediate cell death. Nat Rev Mol Cell Biol 9(1):47\u201359. https:\/\/doi.org\/10.1038\/NRM2308","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"3","key":"2325_CR24","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1164\/RCCM.200503-343OC","volume":"172","author":"Z Zhou","year":"2005","unstructured":"Zhou Z, Kozlowski J, Schuster DP (2005) Physiologic, biochemical, and imaging characterization of acute lung injury in mice. Am J Respir Crit Care Med 172(3):344\u2013351. https:\/\/doi.org\/10.1164\/RCCM.200503-343OC","journal-title":"Am J Respir Crit Care Med"},{"key":"2325_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2020.104077","author":"X Zhu","year":"2020","unstructured":"Zhu X, Wang B, Zhang X, Chen X, Zhu J, Zou Y, Li J (2020) Alpha-linolenic acid protects against lipopolysaccharide-induced acute lung injury through anti-inflammatory and anti-oxidative pathways. Microb Pathog. https:\/\/doi.org\/10.1016\/j.micpath.2020.104077","journal-title":"Microb Pathog"}],"container-title":["Apoptosis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10495-026-02325-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10495-026-02325-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10495-026-02325-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T23:47:27Z","timestamp":1777592847000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10495-026-02325-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,27]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["2325"],"URL":"https:\/\/doi.org\/10.1007\/s10495-026-02325-y","relation":{},"ISSN":["1360-8185","1573-675X"],"issn-type":[{"value":"1360-8185","type":"print"},{"value":"1573-675X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,27]]},"assertion":[{"value":"7 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no conflicts of interest to declare related to this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"113"}}