Skip to main content

Advertisement

SpringerLink
Log in

Evaluation of the protective and therapeutic effects of extra virgin olive oil rich in phenol in experimental model of neonatal necrotizing enterocolitis by clinical disease score, ınflammation, apoptosis, and oxidative stress markers

  • Original Article
  • Published:
Pediatric Surgery International Aims and scope Submit manuscript

Abstract

Background and aim

Necrotizing Enterocolitis (NEC) is an inflammation-associated ischemic necrosis of the intestine. To investigate the effects of extra virgin olive oil (EVOO) on inflammation, oxidative stress, apoptosis, and histological changes in NEC-induced newborn rats.

Materials and methods

24 rats were randomly divided into three groups: control, NEC and NEC + EVOO. NEC induction was performed using hypoxia–hyperoxia, formula feeding, and cold stress. The NEC + EVOO group received 2 ml/kg EVOO with high phenolic content by gavage twice a day for 3 days. 3 cm of bowel including terminal ileum, cecum, and proximal colon was excised.

Results

Weight gain and clinical disease scores were significantly higher in the NEC + EVOO group than in the NEC group (p < 0.001). EVOO treatment caused significant decreases in IL1β, IL6 levels (p = 0.016, p = 0.029 respectively) and EGF, MDA levels (p = 0.032, p = 0.013 respectively) compared to NEC group. Significant decreases were observed in IL6 gene expression in the NEC + EVOO group compared to the NEC group (p = 0.002). In the group NEC + EVOO, the number of Caspase-3 positive cells was found to be significantly reduced (p < 0.001) and histopathological examination revealed minimal changes and significantly lower histopathological scores (p < 0.001).

Conclusion

Phenol-rich EVOO prevents intestinal damage caused by NEC by inhibiting inflammation, oxidative stress, apoptosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data availability

All data in this study are included in the current study. Further information can be required from the corresponding author.

References

  1. Gupta A, Paria A (2016) Etiology and medical management of NEC. Early Hum Dev 97:17–23

    Article  PubMed  Google Scholar 

  2. Wang K, Tao G, Sylvester KG (2019) Recent advances in prevention and therapies for clinical or experimental necrotizing enterocolitis. Dig Dis Sci 64(11):3078–3085

    Article  PubMed  CAS  Google Scholar 

  3. Afrazi A, Sodhi CP, Richardson W, Neal M, Good M, Siggers R et al (2011) New insights into the pathogenesis and treatment of necrotizing enterocolitis: Toll-like receptors and beyond. Pediatr Res 69(3):183–188

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Alganabi M, Lee C, Bindi E, Li B, Pierro A (2019) Recent advances in understanding necrotizing enterocolitis. F1000Res. https://doi.org/10.1268/f1000research.17228.1

    Article  PubMed  PubMed Central  Google Scholar 

  5. Stark AH, Madar Z (2002) Olive oil as a functional food: epidemiology and nutritional approaches. Nutr Rev 60(6):170–176

    Article  PubMed  Google Scholar 

  6. Martinez-Gonzalez MA, Estruch R (2004) Mediterranean diet, antioxidants and cancer: the need for randomized trials. Eur J Cancer Prev 13(4):327–335

    Article  PubMed  CAS  Google Scholar 

  7. Miles EA, Zoubouli P, Calder PC (2005) Differential anti-inflammatory effects of phenolic compounds from extra virgin olive oil identified in human whole blood cultures. Nutrition 21(3):389–394

    Article  PubMed  CAS  Google Scholar 

  8. Cicerale S, Lucas L, Keast R (2010) Biological activities of phenolic compounds present in virgin olive oil. Int J Mol Sci 11(2):458–479

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Cicerale S, Conlan XA, Sinclair AJ, Keast RS (2008) Chemistry and health of olive oil phenolics. Crit Rev Food Sci Nutr 49(3):218–236

    Article  Google Scholar 

  10. Abd Elmaksoud HA, Motawea MH, Desoky AA, Elharrif MG, Ibrahimi A (2021) Hydroxytyrosol alleviate intestinal inflammation, oxidative stress and apoptosis resulted in ulcerative colitis. Biomed Pharmacother 142:112073

    Article  Google Scholar 

  11. Hidalgo M, Prieto I, Abriouel H, Villarejo AB, Ramirez-Sanchez M, Cobo A et al (2018) Changes in gut microbiota linked to a reduction in systolic blood pressure in spontaneously hypertensive rats fed an extra virgin olive oil-enriched diet. Plant Foods Hum Nutr 73(1):1–6

    Article  PubMed  CAS  Google Scholar 

  12. Takashima T, Sakata Y, Iwakiri R, Shiraishi R, Oda Y, Inoue N et al (2014) Feeding with olive oil attenuates inflammation in dextran sulfate sodium-induced colitis in rat. J Nutr Biochem 25(2):186–192

    Article  PubMed  CAS  Google Scholar 

  13. Alarcon de la Lastra C, Barranco MD, Martin MJ, Herrerias J, Motilva V (2002) Extra-virgin olive oil-enriched diets reduce indomethacin-induced gastric oxidative damage in rats. Dig Dis Sci 47(12):2783–2790

    Article  PubMed  CAS  Google Scholar 

  14. Yildiz Gulhan P, Eroz R, Ataoglu O, Ince N, Davran F, Öztürk CE et al (2022) The evaluation of both the expression and serum protein levels of Caspase-3 gene in patients with different degrees of SARS-CoV2 infection. J Med Virol 94(3):897–905

    Article  PubMed  CAS  Google Scholar 

  15. Tasdemir S, Eroz R, Dogan H, Erdem HB, Sahin I, Kara M et al (2016) Association between human hair loss and the expression levels of nucleolin, nucleophosmin, and UBTF genes. Genet Test Mol Biomark 20(4):197–202

    Article  CAS  Google Scholar 

  16. Kabaklıoğlu M, Eroz R, Kaya M (2021) May argyrophilic nucleolar organizer regions be used as a biomarker for the detection of the degree of ischemic damage instead of tunel in testicular torsion? Medicina 57(11):1177

    Article  PubMed  PubMed Central  Google Scholar 

  17. Damar İH, Eroz R (2022) Argyrophilic nucleolar organizer regions as new biomarkers in ST-Elevation myocardial infarction. Journal of Cardiovascular Development and Disease 9(2):58

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kaya M, Eroz R, Kabakliogli M (2022) Expression of nucleolin, nucleophosmin, upstream binding transcription factor genes and propolis in wound models. J Wound Care 31(Sup10):S28–S40

    Article  PubMed  Google Scholar 

  19. Acat M, Yıldız Gülhan P, Eröz R, Ertınmaz Özkan A, Koca O, Çınar C (2023) Evaluation of both expression and serum protein levels of caspase-8 and mitogen-activated protein kinase 1 genes in patients with different severities of COVID-19 infection. Mol Biol Rep 50(4):3241–3248

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Guven A, Gundogdu G, Vurucu S, Uysal B, Oztas E, Ozturk H et al (2009) Medical ozone therapy reduces oxidative stress and intestinal damage in an experimental model of necrotizing enterocolitis in neonatal rats. J Pediatr Surg 44(9):1730–1735

    Article  PubMed  Google Scholar 

  21. Khayyat LI (2021) Extra virgin olive oil protects the testis and blood from the toxicity of paracetamol (overdose) in adult male Rats. Biol (Basel) 10(10):1042

    CAS  Google Scholar 

  22. Zani A, Cordischi L, Cananzi M, De Coppi P, Smith VV, Eaton S et al (2008) Assessment of a neonatal rat model of necrotizing enterocolitis. Eur J Pediatr Surg 18(6):423–426

    Article  PubMed  CAS  Google Scholar 

  23. Martal J, Djiane J, Dubois M, Wooding P, CullingCFA BG, Allison, RT and Barr, WT (1985) Cellular pathology Techniques. Butterworths, London

    Google Scholar 

  24. Caplan MS, Hedlund E, Adler L, Hsueh W (1994) Role of asphyxia and feeding in a neonatal rat model of necrotizing enterocolitis. Pediatr Pathol 14(6):1017–1028

    Article  PubMed  CAS  Google Scholar 

  25. Kromhout D, Kok FJ (2004) Atherosclerosis: epidemiological studies on the health effects of a Mediterranean diet. Eur J Nutr 43(Suppl 1):2–5

    Google Scholar 

  26. Pelucchi C, Bosetti C, Negri E, Lipworth L, La Vecchia C (2011) Olive oil and cancer risk: an update of epidemiological findings through 2010. Curr Pharm Des 17(8):805–812

    Article  PubMed  CAS  Google Scholar 

  27. Fernandes J, Fialho M, Santos R, Peixoto-Placido C, Madeira T, Sousa-Santos N et al (2020) Is olive oil good for you? A systematic review and meta-analysis on anti-inflammatory benefits from regular dietary intake. Nutrition 69:110559

    Article  PubMed  CAS  Google Scholar 

  28. Romani A, Ieri F, Urciuoli S, Noce A, Marrone G, Nediani C et al (2019) Health effects of phenolic compounds found in extra-virgin olive oil, by-products, and leaf of Olea europaea L. Nutrients 11(8):1776

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Armutcu F, Namuslu M, Yüksel R, Kaya M (2013) Zeytinyağı ve sağlık: Biyoaktif bileşenleri, antioksidan özellikleri ve klinik etkileri. Konuralp Medical Journal 5(1):60–68

    Google Scholar 

  30. Parkinson L, Cicerale S (2016) The Health Benefiting Mechanisms of Virgin Olive Oil Phenolic Compounds. Molecules 21(12):1734

    Article  PubMed  PubMed Central  Google Scholar 

  31. Servili M, Sordini B, Esposto S, Urbani S, Veneziani G, Maio ID et al (2013) Biological activities of phenolic compounds of extra virgin olive oil. Antioxidants 3(1):1–23

    Article  PubMed  PubMed Central  Google Scholar 

  32. Surmeli Onay O, Korkmaz A, Yigit S, Yurdakok M (2020) Hypoxic-ischemic enterocolitis: a proposal of a new terminology for early NEC or NEC-like disease in preterm infants, a single-center prospective observational study. Eur J Pediatr 179(4):561–570

    Article  PubMed  CAS  Google Scholar 

  33. Neu J, Walker WA (2011) Necrotizing enterocolitis. N Engl J Med 364(3):255–264

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Hodzic Z, Bolock AM, Good M (2017) The Role of Mucosal Immunity in the Pathogenesis of Necrotizing Enterocolitis. Front Pediatr 5:40

    Article  PubMed  PubMed Central  Google Scholar 

  35. Neu J, Pammi M (2017) Pathogenesis of NEC: impact of an altered intestinal microbiome. In: Neu J, Pammi M (eds) Seminars in Perinatology. Elsevier

    Google Scholar 

  36. Caplan M (2007) Is EGF the holy grail for NEC? J Pediatr 150(4):329–330

    Article  PubMed  Google Scholar 

  37. Kim JH Neonatal necrotizing enterocolitis: Pathology and pathogenesis. Up to Date. https://medilib.ir/uptodate/show/4991 Accessed June 2023 (2019).

  38. Eaton S, Rees CM, Hall NJ (2017) Current Research on the Epidemiology, Pathogenesis, and Management of Necrotizing Enterocolitis. Neonatology 111(4):423–430

    Article  PubMed  Google Scholar 

  39. Martinínez-Domínguez E, De la Puerta R, Ruiz-Gutiérrez V (2001) Protective effects upon experimental inflammation models of a polyphenol-supplemented virgin olive oil diet. Inflamm Res 50:102–106

    Google Scholar 

  40. Karaosmanoglu H, Soyer F, Ozen B, Tokatli F (2010) Antimicrobial and antioxidant activities of Turkish extra virgin olive oils. J Agric Food Chem 58(14):8238–8245

    Article  PubMed  CAS  Google Scholar 

  41. Sodhi C, Richardson W, Gribar S, Hackam DJ (2008) The development of animal models for the study of necrotizing enterocolitis. Dis Model Mech 21(2–3):94–98

    Article  Google Scholar 

  42. Yossuck P, Kraszpulski M, Salm AK (2006) Perinatal corticosteroid effect on amygdala and hippocampus volume during brain development in the rat model. Early Hum Dev 82(4):267–272

    Article  PubMed  CAS  Google Scholar 

  43. Rosignoli P, Fuccelli R, Fabiani R, Servili M, Morozzi G (2013) Effect of olive oil phenols on the production of inflammatory mediators in freshly isolated human monocytes. J Nutr Biochem 24(8):1513–1519

    Article  PubMed  CAS  Google Scholar 

  44. Hering NA, Fromm M, Schulzke JD (2012) Determinants of colonic barrier function in inflammatory bowel disease and potential therapeutics. J Physiol 590(5):1035–1044

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Qi W, Shen Q, Zhang L, Han LP, Wang S (2016) Study on the inflammatory intervention of erythropoietin on NEC. Exp Ther Med 11(6):2221–2224

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Sanchez-Fidalgo S, Cardeno A, Sanchez-Hidalgo M, Aparicio-Soto M, de la Lastra CA (2013) Dietary extra virgin olive oil polyphenols supplementation modulates DSS-induced chronic colitis in mice. J Nutr Biochem 24(7):1401–1413

    Article  PubMed  CAS  Google Scholar 

  47. Campolo M, Di Paola R, Impellizzeri D, Crupi R, Morittu VM, Procopio A et al (2013) Effects of a polyphenol present in olive oil, oleuropein aglycone, in a murine model of intestinal ischemia/reperfusion injury. J Leukoc Biol 93(2):277–287

    Article  PubMed  CAS  Google Scholar 

  48. Wang WC, Xia YM, Yang B, Su XN, Chen JK, Li W et al (2017) Protective Effects of Tyrosol against LPS-Induced Acute Lung Injury via Inhibiting NF-kappaB and AP-1 Activation and Activating the HO-1/Nrf2 Pathways. Biol Pharm Bull 40(5):583–593

    Article  PubMed  CAS  Google Scholar 

  49. Halliwell B (1997) Antioxidants and human disease: a general introduction. Nutr Rev 55:S44–S49

    Article  PubMed  CAS  Google Scholar 

  50. Romero FJ, Bosch-Morell F, Romero MJ, Jareno EJ, Romero B, Marin N et al (1998) Lipid peroxidation products and antioxidants in human disease. Environ Health Perspect 106(Suppl 5):1229–1234

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Kasdallah-Grissa A, Nakbi A, Koubaa N, El-Fazaa S, Gharbi N, Kamoun A et al (2008) Dietary virgin olive oil protects against lipid peroxidation and improves antioxidant status in the liver of rats chronically exposed to ethanol. Nutr Res 28(7):472–479

    Article  PubMed  CAS  Google Scholar 

  52. Mokhtari T, Hussein Osman HE, El-Meghawry El-Kenawy A, Dashti N (2020) Ameliorative effect of virgin olive oil against nephrotoxicity following sub-chronic administration of ethephon in male rats. J Tradit Complement Med 10(5):487–495

    Article  PubMed  Google Scholar 

  53. Egan CE, Sodhi CP, Good M, Lin J, Jia H, Yamaguchi Y et al (2016) Toll-like receptor 4-mediated lymphocyte influx induces neonatal necrotizing enterocolitis. J Clin Invest 126(2):495–508

    Article  PubMed  Google Scholar 

  54. Elgebaly HA, Mosa NM, Allach M, El-Massry KF, El-Ghorab AH, Al Hroob AM et al (2018) Olive oil and leaf extract prevent fluoxetine-induced hepatotoxicity by attenuating oxidative stress, inflammation and apoptosis. Biomed Pharmacother 98:446–453

    Article  PubMed  CAS  Google Scholar 

  55. Visioli F, Galli C, Galli G, Caruso D (2002) Biological activities and metabolic fate of olive oil phenols. Eur J Lipid Sci Technol 104(9–10):677–684

    Article  CAS  Google Scholar 

  56. Khalatbary AR, Mohammadnegad B, Goudarzi G, Fazlollahpour Balef A (2017) Immunohistochemical and electron microscopic study of the inhibitory effects of olive oil polyphenol on dexamethasone-induced apoptosis. Iran J Pathol 12(1):45–52

    Article  PubMed  PubMed Central  Google Scholar 

  57. Isani MA, Delaplain PT, Grishin A, Ford HR (2018) Evolving understanding of neonatal necrotizing enterocolitis. Curr Opin Pediatr 30(3):417–423

    Article  PubMed  Google Scholar 

  58. Warner BW, Warner BB (2005) Role of epidermal growth factor in the pathogenesis of neonatal necrotizing enterocolitis. In: Warner BW, Warner BB (eds) Seminars in Pediatric Surgery. Elsevier

    Google Scholar 

  59. Khailova L, Dvorak K, Arganbright KM, Williams CS, Halpern MD, Dvorak B (2009) Changes in hepatic cell junctions structure during experimental necrotizing enterocolitis: effect of EGF treatment. Pediatr Res 66(2):140–144

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Millman J, Okamoto S, Kimura A, Uema T, Higa M, Yonamine M et al (2020) Metabolically and immunologically beneficial impact of extra virgin olive and flaxseed oils on composition of gut microbiota in mice. Eur J Nutr 59(6):2411–2425

    Article  PubMed  CAS  Google Scholar 

  61. Millman JF, Okamoto S, Teruya T, Uema T, Ikematsu S, Shimabukuro M et al (2021) Extra-virgin olive oil and the gut-brain axis: influence on gut microbiota, mucosal immunity, and cardiometabolic and cognitive health. Nutr Rev 79(12):1362–1374

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was funded by Aksaray Unıversıty—Scientific Research Projects Office (Project No: 2022/022).

Author information

Authors and Affiliations

  1. Department of Pediatric Surgery, Aksaray University Medical Faculty, Aksaray, Turkey

    Mustafa Tuşat

  2. Department of Medical Genetics, Aksaray University Medical Faculty, Aksaray, Turkey

    Recep Eroz & Hüseyin Erdal

  3. Department of Histology and Embryology, Aksaray University Medical Faculty, Aksaray, Turkey

    Ferhan Bölükbaş

  4. Faculty of Veterinary Medicine, Department of Parasitology, Aksaray University, Aksaray, Turkey

    Erkan Özkan

Authors
  1. Mustafa Tuşat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Recep Eroz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ferhan Bölükbaş
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Erkan Özkan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hüseyin Erdal
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M.T contributed to the study conception and design. E.Ö carried out the experimental stages. F.B performed histological and immunohistochemical stainings. M.T. acquired the data. M.T, R.E, F.B, and H.E analyzed and interpreted the data. The first draft of the manuscript was written by M.T, R.E, and all authors commented on previous versions of the manuscript. R.E and M.T critically reviewed the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mustafa Tuşat.

Ethics declarations

Conflict of interests

The authors declare no conflictof interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tuşat, M., Eroz, R., Bölükbaş, F. et al. Evaluation of the protective and therapeutic effects of extra virgin olive oil rich in phenol in experimental model of neonatal necrotizing enterocolitis by clinical disease score, ınflammation, apoptosis, and oxidative stress markers. Pediatr Surg Int 40, 80 (2024). https://doi.org/10.1007/s00383-024-05669-1

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00383-024-05669-1

Keywords

Search

Navigation