{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T14:45:05Z","timestamp":1778769905621,"version":"3.51.4"},"reference-count":49,"publisher":"Georg Thieme Verlag KG","issue":"16","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Perinatol"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:p>\n            Objective\u2003This study aimed to ascertain the effects of astaxanthin (ASX) in an experimental necrotizing enterocolitis (NEC) model using rat pups.<\/jats:p><jats:p>\n            Study Design\u2003Forty-two pups born from five Wistar albino rats were randomly divided into three groups as the control group, NEC\u2009+\u2009placebo (saline), and NEC\u2009+\u2009ASX. Pups in the NEC\u2009+\u2009ASX group were given 100\u2009mg\/kg\/day oral ASX from day 1 to day 4 of the study. Saline of 2\u2009mL\/kg was given to the NEC\u2009+\u2009placebo group. Histopathological, immunohistochemical (caspase-3), and biochemical evaluations including the total antioxidant status (TAS), total oxidant status (TOS), superoxide dismutase (SOD), glutathione (GSH), lipid hydroperoxide (LPO), 8-hydroxydeoxyguanosine (8-OHdG), advanced oxidation protein products (AOPP), myeloperoxidase (MPO), tumor necrosis factor-\u03b1 (TNF-\u03b1), interleukin-1\u03b2 (IL-1\u03b2), and nuclear factor erythroid 2\u2013related factor 2 (Nfr-2) activities were all performed.<\/jats:p><jats:p>\n            Results\u2003A better survival rate and weight gain were demonstrated in the NEC\u2009+\u2009ASX group (p\u2009&lt;\u20090.05). In the histopathological evaluation, the severity of intestinal damage was significantly reduced in the NEC\u2009+\u2009ASX group, as well as decreased apoptosis (enzyme-linked immunosorbent assay [ELISA] for caspase-3; p\u2009=\u20090.001). The biochemical analyses of intestinal tissue TOS, oxidative stress index (OSI; TOS\/TAS), IL-1\u03b2, LPO, 8-OHdG, AOPP, caspase-3 (p\u2009&lt;\u20090.001 for all), and TNF-\u03b1 and MPO (p\u2009=\u20090.001 for both parameters) levels were lower in the NEC\u2009+\u2009ASX group than in the NEC\u2009+\u2009placebo group. Nrf-2, TAS, GSH, and SOD levels were higher in the NEC\u2009+\u2009ASX group than in the NEC\u2009+\u2009placebo group (p\u2009=\u20090.001, 0.001, &lt;0.001, and 0.01, respectively).<\/jats:p><jats:p>\n            Conclusion\u2003ASX treatment has been shown to effectively reduce the severity of intestinal damage in NEC due to its antioxidant, anti-inflammatory, and antiapoptotic properties.<\/jats:p><jats:p>\n            Key Points\n          <\/jats:p>","DOI":"10.1055\/s-0041-1727156","type":"journal-article","created":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T23:15:14Z","timestamp":1618442114000},"page":"1820-1827","source":"Crossref","is-referenced-by-count":16,"title":["Astaxanthin Reduces the Severity of Intestinal Damage in a Neonatal Rat Model of Necrotizing Enterocolitis"],"prefix":"10.1055","volume":"39","author":[{"given":"Hasan","family":"Akduman","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, SBU Ankara Dr. Sami Ulus Maternity Child Health and Diseases Training and Research Hospital, Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cuneyt","family":"Tayman","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Ankara City Hospital, Cankaya, Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veli","family":"Korkmaz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Lokman Hekim University, Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filiz","family":"Akduman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Beypazar\u0131 State Hospital, Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nurdan D.","family":"Fettah","sequence":"additional","affiliation":[{"name":"Department of Neonatology, SBU Ankara Dr. Sami Ulus Maternity Child Health and Diseases Training and Research Hospital, Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ba\u015fak K.","family":"G\u00fcrsoy","sequence":"additional","affiliation":[{"name":"Department of Neonatology, SBU Ankara Dr. Sami Ulus Maternity Child Health and Diseases Training and Research Hospital, Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tugba T.","family":"Turkmenoglu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ankara Diskapi Yildirim Beyzat Training and Research Hospital, Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Murat","family":"\u00c7a\u011flayan","sequence":"additional","affiliation":[{"name":"Department of Medicinal Biochemistry, University of Health Sciences G\u00fclhane Health Sciences Institute, Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2021,4,14]]},"reference":[{"issue":"02","key":"ref1","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1159\/000506866","article-title":"Necrotizing enterocolitis: the future","volume":"117","author":"J Neu","year":"2020","journal-title":"Neonatology"},{"issue":"10","key":"ref2","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/nrgastro.2016.119","article-title":"Necrotizing enterocolitis: new insights into pathogenesis and mechanisms","volume":"13","author":"D F Ni\u00f1o","year":"2016","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"01","key":"ref3","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1053\/j.sempedsurg.2017.11.003","article-title":"Necrotizing enterocolitis: pathophysiology from a historical context","volume":"27","author":"D Hackam","year":"2018","journal-title":"Semin Pediatr 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system","volume":"11","author":"Y Nishida","year":"2007","journal-title":"Carotenoid Sci"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"134","DOI":"10.2331\/fishsci.62.134","article-title":"Carotenoids as singlet oxygen quenchers in marine organisms","volume":"62","author":"N Shimidzu","year":"1996","journal-title":"Fish Sci"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/B978-0-12-396454-0.00048-5","article-title":"Role of astaxanthin in sports nutrition","volume":"48","author":"B Capelli","year":"2013","journal-title":"Nutr Enhanced Sports Performance"},{"issue":"01","key":"ref10","doi-asserted-by":"crossref","first-page":"128","DOI":"10.3390\/md12010128","article-title":"Astaxanthin: sources, extraction, stability, biological activities and its commercial applications--a review","volume":"12","author":"R R Ambati","year":"2014","journal-title":"Mar 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colorimetric method for measuring total oxidant status","volume":"38","author":"O Erel","year":"2005","journal-title":"Clin Biochem"},{"issue":"04","key":"ref24","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.clinbiochem.2003.11.015","article-title":"A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation","volume":"37","author":"O Erel","year":"2004","journal-title":"Clin Biochem"},{"issue":"03","key":"ref25","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1093\/clinchem\/34.3.497","article-title":"A simple method for clinical assay of superoxide dismutase","volume":"34","author":"Y Sun","year":"1988","journal-title":"Clin Chem"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"9478958","DOI":"10.1155\/2017\/9478958","article-title":"The protective effect of naringenin-oxime on cisplatin-induced toxicity in rats","volume":"2017","author":"I 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enterocolitis","volume":"29","author":"C Tayman","year":"2016","journal-title":"J Invest Surg"},{"issue":"S 01","key":"ref34","first-page":"S84","article-title":"Astaxanthin ameliorates hepatic damage and oxidative stress in carbon tetrachloride-administered rats","volume":"9","author":"M A Islam","year":"2017","journal-title":"Pharmacognosy Res"},{"issue":"11","key":"ref35","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1016\/j.jpedsurg.2010.06.024","article-title":"Protective effects of clarithromycin in rats with hypoxia\/reoxygenation-induced intestinal injury","volume":"45","author":"\u00d6M \u00d6zdemir","year":"2010","journal-title":"J Pediatr Surg"},{"issue":"01","key":"ref36","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.pathophys.2013.11.010","article-title":"Inflammatory signaling in NEC: role of NF-\u03baB, cytokines and other inflammatory mediators","volume":"21","author":"C J Hunter","year":"2014","journal-title":"Pathophysiology"},{"issue":"01","key":"ref37","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.cbi.2011.05.006","article-title":"Dietary astaxanthin inhibits colitis and colitis-associated colon carcinogenesis in mice via modulation of the inflammatory cytokines","volume":"193","author":"Y Yasui","year":"2011","journal-title":"Chem Biol Interact"},{"issue":"06","key":"ref38","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1053\/j.gastro.2011.02.016","article-title":"Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases","volume":"140","author":"W Strober","year":"2011","journal-title":"Gastroenterology"},{"issue":"02","key":"ref39","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1097\/MIB.0000000000000654","article-title":"Increased expression of interleukin-36, a member of the interleukin-1 cytokine family, in inflammatory bowel disease","volume":"22","author":"A Nishida","year":"2016","journal-title":"Inflamm Bowel Dis"},{"issue":"01","key":"ref40","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3164\/jcbn.11-006FR","article-title":"Myeloperoxidase-derived oxidation: mechanisms of biological damage and its prevention","volume":"48","author":"M J Davies","year":"2011","journal-title":"J Clin Biochem Nutr"},{"issue":"05","key":"ref41","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.3390\/molecules25051053","article-title":"Quercetin protects against lipopolysaccharide-induced intestinal oxidative stress in broiler chickens through activation of Nrf2 pathway","volume":"25","author":"L Sun","year":"2020","journal-title":"Molecules"},{"issue":"04","key":"ref42","doi-asserted-by":"crossref","first-page":"350","DOI":"10.3390\/antiox9040350","article-title":"Astaxanthin treatment induces maturation and functional change of myeloid-derived suppressor cells in tumor-bearing mice","volume":"9","author":"S M Jeong","year":"2020","journal-title":"Antioxidants"},{"issue":"02","key":"ref43","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.taap.2011.06.018","article-title":"Prenatal administration of the cytochrome P4501A inducer, \u0392-naphthoflavone (BNF), attenuates hyperoxic lung injury in newborn mice: implications for bronchopulmonary dysplasia (BPD) in premature infants","volume":"256","author":"X I Couroucli","year":"2011","journal-title":"Toxicol Appl Pharmacol"},{"issue":"01","key":"ref44","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.biocel.2006.07.001","article-title":"Free radicals and antioxidants in normal physiological functions and human disease","volume":"39","author":"M Valko","year":"2007","journal-title":"Int J Biochem Cell Biol"},{"issue":"01","key":"ref45","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1080\/15569527.2018.1518330","article-title":"The protective effects of astaxanthin against cisplatin-induced retinal 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