Nekrotizan Enterokolitli Yenidoğan Rat Modelinde Silimarinin Antioksidan Etkileri

Yıl 2023, Cilt: 45 Sayı: 1, 28 - 34, 23.01.2023

Emine Esin Yalınbaş , Raziye Akcılar , Havva Koçak , Murat Soner Çirkinoğlu , Mehmet Metineren , Harun Kaçar

https://doi.org/10.20515/otd.1161399

Öz

Nekrotizan enterokolit (NEK), prematüre bebeklerde en sık görülen gastrointestinal problemdir. Bu çalışmanın amacı, NEK modeli oluşturulan yenidoğan sıçanlarda silimarin (SLY)'nin koruyucu ve antioksidan etkilerini değerlendirmektir. Yirmi sekiz Sprague-Dawley sıçanı çalışmaya dahil edildi. Sıçanlar rastgele dört gruba ayrıldı: kontrol (C), C+SLY, NEK ve NEK+SLY. NEK, hiperosmolar enteral formül beslenmesi ile indüklendi, yavru sıçanlar hipoksi ve soğuk stresine maruz bırakıldı. Bağırsak dokusunun makroskopik skorlaması değerlendirildi ve biyokimyasal, histopatolojik inceleme için doku örnekleri alındı. Süperoksit dismutaz (SOD), glutatyon peroksidaz (GPx), nitrik oksit (NO), malondialdehit (MDA), total antioksidan status (TAS), total oksidan status (TOS) ve oksidatif stres indeksi (OSI) düzeyleri biyokimyasal olarak değerlendirildi. NEK+SLY grubunda doku TAS (p = 0,007), SOD (p = 0,004) ve GPx düzeylerinde önemli artış ve NO düzeylerinde azalma vardı. NEK grubunda doku MDA, TOS (p = 0,001) ve OSI (p = 0,001) değerleri anlamlı derecede yüksek saptandı. NEK + SLY grubundaki sıçanların bağırsak dokusu, değerlendirildiğinde NEC grubundaki sıçanlardan daha iyi histopatolojiye sahipti. Silimarin, neonatal sıçanlarda NEK'e karşı faydalı etkilere sahiptir. SLY'nin serbest radikal düzeylerini ve oksidatif stresi azalttığı, antioksidan kapasiteyi arttırdığı ve NEK'e bağlı bağırsak hasarının şiddetini iyileştirdiği görülmektedir.

Anahtar Kelimeler

nekrotizan enterokolit, silimarin, neonatal rat, oksidatif stres

Destekleyen Kurum

Dumlupınar Üniversitesi Bilimsel Araştırmalar Projesi Kurulu

Proje Numarası

2016-36

Antioxidative Effects of Silymarin in A Neonatal Rat Model of Necrotizing Enterocolitis

Öz

Necrotizing enterocolitis (NEC) is the most common gastrointestinal problem in premature infants. The aim of this study is to evaluate the protective and antioxidant effects of silymarin (SLY) in newborn rats with NEC model. Twenty-eight Sprague-Dawley rats were included in the study. The rats were randomized into four groups: control (C), C+SLY, NEC and NEC+SLY. NEC was induced by hyperosmolar enteral formula feeding, and the pups were exposed to hypoxia and cold stress. Macroscopic scoring of the intestinal tissue was evaluated and tissue samples were obtained for biochemical, histopathological examination. Superoxide dismutase (SOD), glutathione peroxidase (GPx), nitric oxide (NO), malondialdehyde (MDA), total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) levels were biochemically evaluated. Results: In the NEC + SLY group, there was a considerable rise in tissue TAS (p = 0.007), SOD (p = 0.004) and GPx levels, as well as a decrease in NO levels. Significantly higher tissue MDA, TOS (p = 0.001) and OSI (p = 0.001) values were detected in the NEC group. The intestinal tissue of rats in the NEC + SLY group had better histopathology than rats in the NEC group when evaluated. Silymarin has beneficial effects against NEC in neonatal rat. It appears that SLY reduces free radical levels and oxidative stress, increases antioxidant capacity, and ameliorates the severity of intestinal damage due to NEC

Anahtar Kelimeler

necrotizing enterocolitis, silymarin, neonatal rats, oxidative stress

Proje Numarası

2016-36

Kaynakça

• 1. Gephart SM, Quinn M. A call to action to fight for equity and end necrotizing enterocolitis disparities. Adv. Neonatal Care 2021;21(5):333–335.
• 2. Rich BS, Dolgin SE. Necrotizing Enterocolitis. Pediatrics in Review 2017; 38(12):552–559.
• 3. Bazacliu C, Neu J. Pathophysiology of Necrotizing Enterocolitis: An Update. Curr Pediatr Rev 2019;15(2):68-87.
• 4. Marseglia L, D'Angelo G, Manti S, et al. Oxidative Stress-Mediated Damage in Newborns with Necrotizing Enterocolitis: A Possible Role of Melatonin. Am J Perinatol 2015;32(10):905-909.
• 5. Abenavoli L, Izzo AA, Milić N, et al. Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. Phytother Res 2018;32(11):2202-2213.
• 6. Sheta NM, Elfeky YA, Boshra SA. Cardioprotective Efficacy of Silymarin Liquisolid in Isoproterenol Prompted Myocardial Infarction in Rats. AAPS PharmSciTech 2020;23;21(3):81.
• 7. Haddadi R, Shahidi Z, Eyvari-Brooshghalan S. Silymarin and neurodegenerative diseases: Therapeutic potential and basic molecular mechanisms. Phytomedicine 2020;79:153320.
• 8. MacDonald-Ramos K, Michán L, Martínez-Ibarra A, et al. Silymarin is an ally against insulin resistance: A review. Ann Hepatol 2021;23:100255.
• 9. Delmas D, Xiao J, Vejux A, et al. Silymarin and Cancer: A Dual Strategy in Both in Chemoprevention and Chemosensitivity. Molecules 2020;25;25(9):2009.
• 10. Surai PF. Silymarin as a Natural Antioxidant: An Overview of the Current Evidence and Perspectives. Antioxidants (Basel) 2015;4(1):204-247.
• 11. Liu CH, Jassey A, Hsu HY, et al. Antiviral Activities of Silymarin and Derivatives. Molecules 2019;24(8):1552.
• 12. Guven A, Uysal B, Gundogdu G, et al. Melatonin ameliorates necrotizing enterocolitis in a neonatal rat model. J Pediatr Surg 2011;46(11):2101-2107.
• 13. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 2004;37:277-285.
• 14. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005;38:1103-1111.
• 15. Shinyama S, Kaji T, Mukai M, et al. The novel preventive effect of Daikenchuto (TJ-100), a Japanese herbal drug, against neonatal necrotizing enterocolitis in rats. Pediatr Surg Int 2017;33(10):1109-1114.
• 16. Jing Y, Peng F, Shan Y, et al. Berberine reduces the occurrence of neonatal necrotizing enterocolitis by reducing the inflammatory response. Exp Ther Med 2018;16(6):5280-5285.
• 17. Cigsar EB, Karadag CA, Tanik C, et al. The protective effects of sesamol in a neonatal rat model of necrotizing enterocolitis. J Matern Fetal Neonatal Med 2020;33(6):889-894.
• 18. Nadler EP, Dickinson E, Knisely A, et al. Expression of inducible nitric oxide synthase and interleukin-12 in experimental necrotizing enterocolitis. J Surg Res 2000;92:71-7.
• 19. Zamora R, Bryan NS, Boyle P, et al. Nitrosative stress in an animal model of necrotizing enterocolitis. Free Radic Biol Med 2005;39:1428-37.
• 20. Grishin A, Bowling J, Bell B, et al. Roles of nitric oxide and intestinal microbiota in the pathogenesis of necrotizing enterocolitis. J Pediatr Surg 2016;51(1):13-17.
• 21. Upperman JS, Potoka D, Grishin A, et al. Mechanisms of nitric oxide-mediated intestinal barrier failure in necrotizing enterocolitis. Semin Pediatr Surg 2005;14(3):159-166.
• 22. Aydemir C, Dilli D, Uras N, et al. Total oxidant status and oxidative stress are increased in infants with necrotizing enterocolitis. J Pediatr Surg 2011;46(11):2096–2100.
• 23. Yazıcı S, Akşit H, Korkut O, et al. Effects of boric acid and 2-aminoethoxydiphenyl borate on necrotizing enterocolitis. J Pediatr Gastroenterol Nutr 2014;58(01):61–67.
• 24. Tayman C, Tonbul A, Kosus A, et al. Protective effects of caffeic acid phenethyl ester (CAPE) on intestinal damage in necrotizing enterocolitis. Pediatr Surg Int 2011;27(11):1179–1189.
• 25. Akduman H, Tayman C, Korkmaz V, et al. Astaxanthin reduces the severity of ıntestinal damage in a neonatal rat model of necrotizing enterocolitis. Am J Perinatol 2021;doi: 10.1055/s-0041 1727156.
• 26. Hellerbrand C, Schattenberg JM, Peterburs P, et al. The potential of silymarin for the treatment of hepatic disorders. Clin. Phytosc 2016;2, 7–20.
• 27. Federico A, Dallio M, Loguercio C. Silymarin/silybin and chronic liver disease: A marriage of many years. Molecules 2017;24;22(2):191.
• 28. Raghu R, Karthikeyan S. Zidovudine and isoniazid induced liver toxicity and oxidative stress: Evaluation of mitigating properties of silibinin. Environ Toxicol Pharmacol 2016;46:217-226.
• 29. Gabrielová E, Křen V, Jabůrek M, et al. Silymarin component 2,3-dehydrosilybin attenuates cardiomyocyte damage following hypoxia/reoxygenation by limiting oxidative stress. Physiol Res 2015;64(1):79-91.
• 30. Abdulrazzaq AM, Badr M, Gammoh O, et al. Hepatoprotective Actions of Ascorbic Acid, Alpha Lipoic Acid and Silymarin or Their Combination Against Acetaminophen-Induced Hepatotoxicity in Rats. Medicina (Kaunas) 2019;55(5):181.
• 31. Sabina EP, Peter SJ, Geetha A. A comparison of hepatoprotective activity of Bacoside to Silymarin treatment against a combined Isoniazid and Rifampin-induced hepatotoxicity in female Wistar rats. J Histotechnol 2019;42(3):128-136.
• 32. Jouhari S, Mohammadzadeh A, Soltanghoraee H, et al. Effects of silymarin, cabergoline and letrozole on rat model of endometriosis. Taiwan J Obstet Gynecol 2018;57(6):830-835.
• 33. Ghaznavi H, Mehrzadi S, Dormanesh B, et al. Comparison of the Protective Effects of Melatonin and Silymarin Against Gentamicin-Induced Nephrotoxicity in Rats. J Evid Based Complementary Altern Med 2016;21(4):NP49-55.
• 34. Mazhari S, Razi M, Sadrkhanlou R. Silymarin and celecoxib ameliorate experimental varicocele-induced pathogenesis: evidences for oxidative stress and inflammation inhibition. Int Urol Nephrol 2018;50(6):1039-1052.