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Am J Perinatol 2022; 39(16): 1820-1827
DOI: 10.1055/s-0041-1727156
Original Article

Astaxanthin Reduces the Severity of Intestinal Damage in a Neonatal Rat Model of Necrotizing Enterocolitis

Hasan Akduman
1   Division of Neonatology, Department of Pediatrics, SBU Ankara Dr. Sami Ulus Maternity Child Health and Diseases Training and Research Hospital, Ankara, Turkey
,
Cuneyt Tayman
2   Department of Neonatology, Ankara City Hospital, Cankaya, Ankara, Turkey
,
Veli Korkmaz
3   Department of Pediatrics, Lokman Hekim University, Ankara, Turkey
,
Filiz Akduman
4   Department of Pediatrics, Beypazarı State Hospital, Ankara, Turkey
,
Nurdan D. Fettah
5   Department of Neonatology, SBU Ankara Dr. Sami Ulus Maternity Child Health and Diseases Training and Research Hospital, Ankara, Turkey
,
Başak K. Gürsoy
5   Department of Neonatology, SBU Ankara Dr. Sami Ulus Maternity Child Health and Diseases Training and Research Hospital, Ankara, Turkey
,
Tugba T. Turkmenoglu
6   Department of Pathology, Ankara Diskapi Yildirim Beyzat Training and Research Hospital, Ankara, Turkey
,
Murat Çağlayan
7   Department of Medicinal Biochemistry, University of Health Sciences Gülhane Health Sciences Institute, Ankara, Turkey
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Abstract

Objective This study aimed to ascertain the effects of astaxanthin (ASX) in an experimental necrotizing enterocolitis (NEC) model using rat pups.

Study Design Forty-two pups born from five Wistar albino rats were randomly divided into three groups as the control group, NEC + placebo (saline), and NEC + ASX. Pups in the NEC + ASX group were given 100 mg/kg/day oral ASX from day 1 to day 4 of the study. Saline of 2 mL/kg was given to the NEC + placebo 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-α (TNF-α), interleukin-1β (IL-1β), and nuclear factor erythroid 2–related factor 2 (Nfr-2) activities were all performed.

Results A better survival rate and weight gain were demonstrated in the NEC + ASX group (p < 0.05). In the histopathological evaluation, the severity of intestinal damage was significantly reduced in the NEC + ASX group, as well as decreased apoptosis (enzyme-linked immunosorbent assay [ELISA] for caspase-3; p = 0.001). The biochemical analyses of intestinal tissue TOS, oxidative stress index (OSI; TOS/TAS), IL-1β, LPO, 8-OHdG, AOPP, caspase-3 (p < 0.001 for all), and TNF-α and MPO (p = 0.001 for both parameters) levels were lower in the NEC + ASX group than in the NEC + placebo group. Nrf-2, TAS, GSH, and SOD levels were higher in the NEC + ASX group than in the NEC + placebo group (p = 0.001, 0.001, <0.001, and 0.01, respectively).

Conclusion ASX treatment has been shown to effectively reduce the severity of intestinal damage in NEC due to its antioxidant, anti-inflammatory, and antiapoptotic properties.

Key Points

  • NEC causes extremely high morbidity and mortality, as well as many complications.

  • We investigated the effectiveness of ASX in the experimental NEC model created in rat pups.

  • First study examining the effect of ASX on the experimental NEC rat model.

Keywords

astaxanthin - necrotizing enterocolitis - bowel - rat


Publication History

Article published online:
14 April 2021

© 2021. Thieme. All rights reserved.

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333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

Letter to this article:

Letter to the Editor: Astaxanthin Reduces the Severity of Intestinal Damage in a Neonatal Rat Model of Necrotizing EnterocolitisAm J Perinatol 2023; 40(11): 1171-1172
DOI: 10.1055/a-1768-3357

 

  • References

  • 1 Neu J. Necrotizing enterocolitis: the future. Neonatology 2020; 117 (02) 240-244
    CrossrefPubMedGoogle Scholar
  • 2 Niño DF, Sodhi CP, Hackam DJ. Necrotizing enterocolitis: new insights into pathogenesis and mechanisms. Nat Rev Gastroenterol Hepatol 2016; 13 (10) 590-600
    CrossrefPubMedGoogle Scholar
  • 3 Hackam D, Caplan M. Necrotizing enterocolitis: pathophysiology from a historical context. Semin Pediatr Surg 2018; 27 (01) 11-18
    CrossrefPubMedGoogle Scholar
  • 4 Bazacliu C, Neu J. Necrotizing enterocolitis: long term complications. Curr Pediatr Rev 2019; 15 (02) 115-124
    CrossrefPubMedGoogle Scholar
  • 5 Neu J. Necrotizing enterocolitis: the mystery goes on. Neonatology 2014; 106 (04) 289-295
    CrossrefPubMedGoogle Scholar
  • 6 Brown DR, Gough LA, Deb SK, Sparks SA, McNaughton LR. Astaxanthin in exercise metabolism, performance and recovery: a review. Front Nutr 2018; 4 (76) 76
    CrossrefPubMedGoogle Scholar
  • 7 Nishida Y, Yamashita E, Miki W. Quenching activities of common hydrophilic and lipophilic antioxidants against singlet oxygen using chemiluminescence detection system. Carotenoid Sci 2007; 11: 16-20
    PubMedGoogle Scholar
  • 8 Shimidzu N, Goto M, Miki W. Carotenoids as singlet oxygen quenchers in marine organisms. Fish Sci 1996; 62: 134-137
    CrossrefPubMedGoogle Scholar
  • 9 Capelli B, Jenkins U, Cysewski GR. Role of astaxanthin in sports nutrition. Nutr Enhanced Sports Performance 2013; 48: 465-471
    CrossrefPubMedGoogle Scholar
  • 10 Ambati RR, Phang SM, Ravi S, Aswathanarayana RG. Astaxanthin: sources, extraction, stability, biological activities and its commercial applications--a review. Mar Drugs 2014; 12 (01) 128-152
    CrossrefPubMedGoogle Scholar
  • 11 Yang C, Hassan YI, Liu R. et al. Anti-inflammatory effects of different astaxanthin isomers and the roles of lipid transporters in the cellular transport of astaxanthin isomers in caco-2 cell monolayers. J Agric Food Chem 2019; 67 (22) 6222-6231
    CrossrefPubMedGoogle Scholar
  • 12 Chen JT, Kotani K. Astaxanthin as a potential protector of liver function: a review. J Clin Med Res 2016; 8 (10) 701-704
    CrossrefPubMedGoogle Scholar
  • 13 Liu H, Liu M, Fu X. et al. Astaxanthin prevents alcoholic fatty liver disease by modulating mouse gut microbiota. Nutrients 2018; 10 (09) 1298
    CrossrefPubMedGoogle Scholar
  • 14 Zhang L, Cao W, Gao Y. et al. Astaxanthin (ATX) enhances the intestinal mucosal functions in immunodeficient mice. Food Funct 2020; 11 (04) 3371-3381
    CrossrefPubMedGoogle Scholar
  • 15 Baralic I, Andjelkovic M, Djordjevic B. et al. Effect of astaxanthin supplementation on salivary IgA, oxidative stress, and inflammation in young soccer players. Evid Based Complement Alternat Med 2015; 2015: 783761
    CrossrefPubMedGoogle Scholar
  • 16 Sakai S, Nishida A, Ohno M. et al. Astaxanthin, a xanthophyll carotenoid, prevents development of dextran sulphate sodium-induced murine colitis. J Clin Biochem Nutr 2019; 64 (01) 66-72
    CrossrefPubMedGoogle Scholar
  • 17 Guo S, Al-Sadi R, Said HM, Ma TY. Lipopolysaccharide causes an increase in intestinal tight junction permeability in vitro and in vivo by inducing enterocyte membrane expression and localization of TLR-4 and CD14. Am J Pathol 2013; 182 (02) 375-387
    CrossrefPubMedGoogle Scholar
  • 18 Zhou L, Gao M, Xiao Z, Zhang J, Li X, Wang A. Protective effect of astaxanthin against multiple organ injury in a rat model of sepsis. J Surg Res 2015; 195 (02) 559-567
    CrossrefPubMedGoogle Scholar
  • 19 Nagayama T, Sugimoto M, Ikeda S, Kume S. Effects of astaxanthin-enriched yeast on mucosal IgA induction in the jejunum and ileum of weanling mice. Anim Sci J 2014; 85 (04) 449-453
    CrossrefPubMedGoogle Scholar
  • 20 Zani A, Cordischi L, Cananzi M. et al. Assessment of a neonatal rat model of necrotizing enterocolitis. Eur J Pediatr Surg 2008; 18 (06) 423-426
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Caplan MS, Hedlund E, Adler L, Hsueh W. Role of asphyxia and feeding in a neonatal rat model of necrotizing enterocolitis. Pediatr Pathol 1994; 14 (06) 1017-1028
    CrossrefPubMedGoogle Scholar
  • 22 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193 (01) 265-275
    CrossrefPubMedGoogle Scholar
  • 23 Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005; 38 (12) 1103-1111
    CrossrefPubMedGoogle Scholar
  • 24 Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 2004; 37 (04) 277-285
    CrossrefPubMedGoogle Scholar
  • 25 Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988; 34 (03) 497-500
    CrossrefPubMedGoogle Scholar
  • 26 Koyuncu I, Kocyigit A, Gonel A, Arslan E, Durgun M. The protective effect of naringenin-oxime on cisplatin-induced toxicity in rats. Biochem Res Int 2017; 2017: 9478958
    CrossrefPubMedGoogle Scholar
  • 27 Krawisz JE, Sharon P, Stenson WF. Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models. Gastroenterology 1984; 87 (06) 1344-1350
    CrossrefPubMedGoogle Scholar
  • 28 Witko-Sarsat V, Gausson V, Nguyen A-T. et al. AOPP-induced activation of human neutrophil and monocyte oxidative metabolism: a potential target for N-acetylcysteine treatment in dialysis patients. Kidney Int 2003; 64 (01) 82-91
    CrossrefPubMedGoogle Scholar
  • 29 Choi YY. Necrotizing enterocolitis in newborns: update in pathophysiology and newly emerging therapeutic strategies. Korean J Pediatr 2014; 57 (12) 505-513
    CrossrefPubMedGoogle Scholar
  • 30 Kumar S, Singh SV. Inhibition of NF-κB signaling pathway by astaxanthin supplementation for prevention of heat stress-induced inflammatory changes and apoptosis in Karan Fries heifers. Trop Anim Health Prod 2019; 51 (05) 1125-1134
    CrossrefPubMedGoogle Scholar
  • 31 Galasso C, Corinaldesi C, Sansone C. Carotenoids from marine organisms: biological functions and industrial applications. Antioxidants 2017; 6 (04) E96
    CrossrefPubMedGoogle Scholar
  • 32 D'Angelo G, Chimenz R, Reiter RJ, Gitto E. Use of melatonin in oxidative stress related neonatal diseases. Antioxidants 2020; 9 (06) 477
    CrossrefPubMedGoogle Scholar
  • 33 Tayman C, Aydemir S, Yakut I. et al. TNF-α blockade efficiently reduced severe intestinal damage in necrotizing enterocolitis. J Invest Surg 2016; 29 (04) 209-217
    CrossrefPubMedGoogle Scholar
  • 34 Islam MA, Al Mamun MA, Faruk M. et al. Astaxanthin ameliorates hepatic damage and oxidative stress in carbon tetrachloride-administered rats. Pharmacognosy Res 2017; 9 (Suppl. 01) S84-S91
    PubMedGoogle Scholar
  • 35 Özdemir ÖM, Ergin H, Yenisey Ç, Türk NŞ, Şimşek NG. Protective effects of clarithromycin in rats with hypoxia/reoxygenation-induced intestinal injury. J Pediatr Surg 2010; 45 (11) 2169-2174
    CrossrefPubMedGoogle Scholar
  • 36 Hunter CJ, De Plaen IG. Inflammatory signaling in NEC: role of NF-κB, cytokines and other inflammatory mediators. Pathophysiology 2014; 21 (01) 55-65
    CrossrefPubMedGoogle Scholar
  • 37 Yasui Y, Hosokawa M, Mikami N, Miyashita K, Tanaka T. Dietary astaxanthin inhibits colitis and colitis-associated colon carcinogenesis in mice via modulation of the inflammatory cytokines. Chem Biol Interact 2011; 193 (01) 79-87
    CrossrefPubMedGoogle Scholar
  • 38 Strober W, Fuss IJ. Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases. Gastroenterology 2011; 140 (06) 1756-1767
    CrossrefPubMedGoogle Scholar
  • 39 Nishida A, Hidaka K, Kanda T. et al. Increased expression of interleukin-36, a member of the interleukin-1 cytokine family, in inflammatory bowel disease. Inflamm Bowel Dis 2016; 22 (02) 303-314
    CrossrefPubMedGoogle Scholar
  • 40 Davies MJ. Myeloperoxidase-derived oxidation: mechanisms of biological damage and its prevention. J Clin Biochem Nutr 2011; 48 (01) 8-19
    CrossrefPubMedGoogle Scholar
  • 41 Sun L, Xu G, Dong Y, Li M, Yang L, Lu W. Quercetin protects against lipopolysaccharide-induced intestinal oxidative stress in broiler chickens through activation of Nrf2 pathway. Molecules 2020; 25 (05) 1053
    CrossrefPubMedGoogle Scholar
  • 42 Jeong SM, Kim YJ. Astaxanthin treatment induces maturation and functional change of myeloid-derived suppressor cells in tumor-bearing mice. Antioxidants 2020; 9 (04) 350
    CrossrefPubMedGoogle Scholar
  • 43 Couroucli XI, Liang YH, Jiang W. et al. Prenatal administration of the cytochrome P4501A inducer, Β-naphthoflavone (BNF), attenuates hyperoxic lung injury in newborn mice: implications for bronchopulmonary dysplasia (BPD) in premature infants. Toxicol Appl Pharmacol 2011; 256 (02) 83-94
    CrossrefPubMedGoogle Scholar
  • 44 Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007; 39 (01) 44-84
    CrossrefPubMedGoogle Scholar
  • 45 Fındık H, Tumkaya L, Yılmaz A. et al. The protective effects of astaxanthin against cisplatin-induced retinal toxicity. Cutan Ocul Toxicol 2019; 38 (01) 59-65
    CrossrefPubMedGoogle Scholar
  • 46 Good M, Sodhi CP, Egan CE. et al. Breast milk protects against the development of necrotizing enterocolitis through inhibition of Toll-like receptor 4 in the intestinal epithelium via activation of the epidermal growth factor receptor. Mucosal Immunol 2015; 8 (05) 1166-1179
    CrossrefPubMedGoogle Scholar
  • 47 Li P, Fu D, Sheng Q, Yu S, Bao X, Lv Z. TUDCA attenuates intestinal injury and inhibits endoplasmic reticulum stress-mediated intestinal cell apoptosis in necrotizing enterocolitis. Int Immunopharmacol 2019; 74: 105665
    CrossrefPubMedGoogle Scholar
  • 48 Liang S, Lai P, Li X. et al. Ulinastatin reduces the severity of intestinal damage in the neonatal rat model of necrotizing enterocolitis. Med Sci Monit 2019; 25: 9123-9130
    CrossrefPubMedGoogle Scholar
  • 49 Egan CE, Sodhi CP, Good M. et al. Toll-like receptor 4-mediated lymphocyte influx induces neonatal necrotizing enterocolitis. J Clin Invest 2016; 126 (02) 495-508
    CrossrefPubMedGoogle Scholar