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Gastroprotective effect of tarantula cubensis extract in the indomethacin-induced peptic ulcer model in rats

Yıl 2020, Cilt 4, Sayı 3, 278 - 284, 29.10.2020
https://doi.org/10.30565/medalanya.797406

Öz

Aim: Gastric ulcers are the most common gastrointestinal disease, due to several factors in the industrialized world. They may also occur after many pharmacological agents, combined with gastroprotective agents such as proton pump inhibitors (PPI) or anti-acids, are used as a preferred approach to maintaining gastrointestinal health. Unexpected adverse effects in these combinations make natural products an important alternative option.

Methods: Therefore, the main aim of this study is to investigate one natural compound, the Tarantula cubensis extract (TCE), in the experimental peptic ulcer model which was created by a single administration of indomethacin (40 mg/kg, body weight) to fed state Wistar-albino rats. The animals were pre-treated with two-doses of the TCE (0.2 ml/kg) before the indomethacin administration. After six hours, they were euthanized and the stomach tissue was isolated for biochemical and immunohistochemical analysis. Total antioxidant status/total oxidant status (TAS/TOS), prostaglandin E2 (PGE2), and nuclear factor kappa-B (NF-κB) levels were determined with ELISA in tissue homogenates. Caspase-3, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α), were visualized with immunohistochemistry in intact tissues.

Results: Pre-treatment with TCE increased PGE2 levels and decreased total oxidative status (TAS/TOS). Additionally, TCE alleviated the increase of (NF-κB) levels due to the indomethacin administration. Histopathological and immunostaining results showed that TCE mitigated elevated immunoreactivity of the caspase-3, COX-2, iNOS, and TNF-α which were the results of the indomethacin administration.

Conclusion: Our study demonstrated that pre-TCE treatment ameliorated indomethacin-induced peptic ulcers via antioxidant and anti-inflammatory actions.

Kaynakça

  • 1. Graham DY. History of Helicobacter pylori, duodenal ulcer, gastric ulcer and gastric cancer. World J Gastroenterol 2014; 20(18): 5191-5204. doi:10.3748/wjg.v20.i18.5191
  • 2. Mabeku LBK, Nana BN, Bille BE, Tchuenguem RT, Nguepi E. Anti-helicobacter pylori and antiulcerogenic activity of Aframomum pruinosum seeds on indomethacin-induced gastric ulcer in rats. Pharm Biol 2017; 55(1): 929-936. doi:10.1080/13880209.2017.1285326
  • 3. Chen P, Shen Y, Shi H, et al. Gastroprotective effects of Kangfuxin-against ethanol-induced gastric ulcer via attenuating oxidative stress and ER stress in mice. Chem Biol Interact 2016; 260: 75-83. doi:10.1016/j.cbi.2016.10.021
  • 4. Kinoshita Y, Ishimura N, Ishihara S. Advantages and disadvantages of long-term proton pump inhibitor use. J Neurogastroenterol Motil 2018; 24(2): 182-196. doi:10.5056/jnm18001
  • 5. Repetto MG, Llesuy SF. Antioxidant properties of natural compounds used in popular medicine for gastric ulcers. Brazilian J Med Biol Res 2002; 35(5): 523-534. doi:10.1590/S0100-879X2002000500003
  • 6. Kuna L, Jakab J, Smolic R, Raguz-Lucic N, Vcev A, Smolic M. Peptic Ulcer Disease: A Brief Review of Conventional Therapy and Herbal Treatment Options. J Clin Med 2019; 8(2): 179. doi:10.3390/jcm8020179
  • 7. Duz E, Icen H, Arserrim NB, Cakmak F, Bakir B, Uysal E. Comparison of classic, theranekron and classic-plus Theranekron treatment on the foot and mouth disease lesions in cattle in Van, Diyarbakir and Ankara regions in Turkey. J Anim Vet Adv 2012; 11(18): 3258-3261. doi:10.3923/javaa.2012.3258.3261
  • 8. Kizilay Z, Aktas S, Kahraman Cetin N, Kilic MA, Ozturk H. Effect of Tarantula cubensis extract (Theranekron) on peripheral nerve healing in an experimental sciatic nerve injury model in rats. Turk Neurosurg 2019; 29(5): 743-749. doi:10.5137/1019-5149.JTN.26162-19.2
  • 9. Gül Satar NY, Cangül IT, Topal A, Kurt H, Ipek V, Onel GI. The effects of Tarantula cubensis venom on open wound healing in rats. J Wound Care 2017; 26(2): 66-71. doi:10.12968/jowc.2017.26.2.66
  • 10. Oryan A, Moshiri A, Raayat AR. Novel application of Theranekron® enhanced the structural and functional performance of the tenotomized tendon in rabbits. Cells Tissues Organs 2012; 196(5): 442-455. doi:10.1159/000337860
  • 11. Oluwabunmi I, Abiola T. Gastroprotective effect of methanolic extract of Gomphrena celosioides on indomethacin induced gastric ulcer in Wistar albino rats. Int J Appl Basic Med Res 2015; 5(1): 41. doi:10.4103/2229-516x.149238
  • 12. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193(1): 265-275. doi:10.1016/0922-338X(96)89160-4
  • 13. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005; 38(12): 1103-1111. doi:10.1016/j.clinbiochem.2005.08.008
  • 14. Lichtenberger LM. The Hydrophobic Barrier Properties of Gastrointestinal Mucus. Annu Rev Physiol 1995; 57(1): 565-583. doi:10.1146/annurev.ph.57.030195.003025
  • 15. Takeuchi K. Prostaglandin EP Receptors and Their Roles in Mucosal Protection and Ulcer Healing in the Gastrointestinal Tract. Adv Clin Chem 2010; 51(C): 121-144. doi:10.1016/S0065-2423(10)51005-9
  • 16. Utsumi H, Yasukawa K, Soeda T, et al. Noninvasive mapping of reactive oxygen species by in vivo electron spin resonance spectroscopy in indomethacin-induced gastric ulcers in rats. J Pharmacol Exp Ther 2006; 317(1): 228-235. doi:10.1124/jpet.105.095166
  • 17. Ghiselli A, Serafini M, Natella F, Scaccini C. Total antioxidant capacity as a tool to assess redox status: Critical view and experimental data. Free Radic Biol Med 2000; 29(11): 1106-1114. doi:10.1016/S0891-5849(00)00394-4
  • 18. Abdel-Raheem IT. Gastroprotective effect of rutin against indomethacin-induced ulcers in rats. Basic Clin Pharmacol Toxicol 2010; 107(3): 742-750. doi:10.1111/j.1742-7843.2010.00568.x
  • 19. Farzaei MH, Abdollahi M, Rahimi R. Role of dietary polyphenols in the management of peptic ulcer. World J Gastroenterol 2015; 21(21): 6499-6517. doi:10.3748/wjg.v21.i21.6499
  • 20. Chattopadhyay S, Adhikary B, Yadav SK, Roy K, Bandyopadhyay SK. Black tea and theaflavins assist healing of indomethacin-induced gastric ulceration in mice by antioxidative action. Evidence-based Complement Altern Med 2011; 2011: 546560. doi:10.1155/2011/546560
  • 21. Taira K, Watanabe T, Tanigawa T, et al. Roles of cyclooxygenase-2 and prostaglandin E receptors in gastric mucosal defense in Helicobacter pylori-infected mice. Inflammopharmacology 2007; 15(3): 132-138. doi:10.1007/s10787-006-1561-1
  • 22. Takeuchi K. Pathogenesis of NSAID-induced gastric damage: Importance of cyclooxygenase inhibition and gastric hypermotility. World J Gastroenterol 2012; 18(18): 2147-2160. doi:10.3748/wjg.v18.i18.2147
  • 23. Bertrand V, Guessous F, Le Roy AL, et al. Copper-indomethacinate associated with zwitterionic phospholipids prevents enteropathy in rats: Effect on inducible no synthase. Dig Dis Sci 1999; 44(5): 991-999. doi:10.1023/A:1026668816189
  • 24. Abood WN, Abdulla MA, Ismail S. Involvement of inflammatory mediators in the gastroprotective action of Phaleria macrocarpa against ethanol-induced gastric ulcer. World Appl Sci J 2014; 30(30 A): 344-350. doi:10.5829/idosi.wasj.2014.30.icmrp.48
  • 25. Wallace JL. Nitric oxide in the gastrointestinal tract: opportunities for drug development. Br J Pharmacol 2019; 176(2): 147-154. doi:10.1111/bph.14527
  • 26. El-Ela FIA, Farghali AA, Mahmoud RK, Mohamed NA, Moaty SAA. New Approach in Ulcer Prevention and Wound Healing Treatment using Doxycycline and Amoxicillin/LDH Nanocomposites. Sci Rep 2019; 9(1): 6418. doi:10.1038/s41598-019-42842-2

Sıçanlarda indometazin ile indüklenmiş peptik ülser modelinde tarantula cubensis ekstraktının gastroprotektif etkisi

Yıl 2020, Cilt 4, Sayı 3, 278 - 284, 29.10.2020
https://doi.org/10.30565/medalanya.797406

Öz

Amaç: Gastrik ülser, endüstrileşmiş dünyada çeşitli faktörler nedeniyle en sık görülen gastrointestinal hastalıktır. Bununla birlikte mide ülseri, gastrointestinal sağlığın korunması için genellikle tercih edilen proton pompa inhibitörleri (PPI) veya anti-asitler gibi birçok gastroprotektif farmakolojik ajanın kombine kullanılmasından sonra da nüks edebilmektedir. Bu kombinasyonlardaki beklenmedik olumsuz etkiler doğal ürünleri alternatif bir seçenek haline getirir. Bu nedenle, bu çalışmanın temel amacı, tek bir indometasin (40 mg/kg) ile oluşturulan deneysel peptik ülser modelinde doğal bileşiklerden biri olan Tarantula cubensis (TCE) ekstraktının etkisinin araştırılmasıdır.

Yöntemler: İndometazin uygulanmasından önce iki doz TCE (0.2 ml/kg) s.k yoldan uygulanmıştır. Tek doz Indometazin (40 mg/kg) uygulamasından altı saat sonra anestezi altında mide dokusu biyokimyasal ve immünohistokimyasal analiz için çıkarılmıştır. Total antioksidan durum/total oksidan durum (TAS/TOS), prostaglandin E2 (PGE2) ve nükleer faktör kappa-B (NF-κB) düzeyleri doku homojenatlarında ELISA ile belirlenmiştir. Kaspaz-3, siklooksijenaz-2 (COX-2), indüklenebilir nitrik oksit sentaz (iNOS) ve tümör nekroz faktörü-alfa (TNF-α) immünohistokimya ile görüntülenmiştir.

Bulgular: TCE ile ön tedavi PGE2 düzeylerini artırdı ve toplam oksidatif durumu (TAS / TOS) azaltmıştır. Ek olarak, TCE indometazin uygulamasına bağlı olarak NF-κB düzeylerindeki artışı hafifletmiştir. Histopatolojik ve immünboyama sonuçları, TCE'nin, indometazin uygulamasının sonuçları olan kaspaz-3, COX-2, iNOS ve TNF-α'nın yüksek immünoreaktivitesini azalttığını göstermiştir.

Sonuç: Çalışmamız TCE tedavisinin, antioksidan ve antiinflamatuvar etkiler yoluyla indometazine bağlı peptik ülserleri iyileştirdiğini göstermiştir.

Kaynakça

  • 1. Graham DY. History of Helicobacter pylori, duodenal ulcer, gastric ulcer and gastric cancer. World J Gastroenterol 2014; 20(18): 5191-5204. doi:10.3748/wjg.v20.i18.5191
  • 2. Mabeku LBK, Nana BN, Bille BE, Tchuenguem RT, Nguepi E. Anti-helicobacter pylori and antiulcerogenic activity of Aframomum pruinosum seeds on indomethacin-induced gastric ulcer in rats. Pharm Biol 2017; 55(1): 929-936. doi:10.1080/13880209.2017.1285326
  • 3. Chen P, Shen Y, Shi H, et al. Gastroprotective effects of Kangfuxin-against ethanol-induced gastric ulcer via attenuating oxidative stress and ER stress in mice. Chem Biol Interact 2016; 260: 75-83. doi:10.1016/j.cbi.2016.10.021
  • 4. Kinoshita Y, Ishimura N, Ishihara S. Advantages and disadvantages of long-term proton pump inhibitor use. J Neurogastroenterol Motil 2018; 24(2): 182-196. doi:10.5056/jnm18001
  • 5. Repetto MG, Llesuy SF. Antioxidant properties of natural compounds used in popular medicine for gastric ulcers. Brazilian J Med Biol Res 2002; 35(5): 523-534. doi:10.1590/S0100-879X2002000500003
  • 6. Kuna L, Jakab J, Smolic R, Raguz-Lucic N, Vcev A, Smolic M. Peptic Ulcer Disease: A Brief Review of Conventional Therapy and Herbal Treatment Options. J Clin Med 2019; 8(2): 179. doi:10.3390/jcm8020179
  • 7. Duz E, Icen H, Arserrim NB, Cakmak F, Bakir B, Uysal E. Comparison of classic, theranekron and classic-plus Theranekron treatment on the foot and mouth disease lesions in cattle in Van, Diyarbakir and Ankara regions in Turkey. J Anim Vet Adv 2012; 11(18): 3258-3261. doi:10.3923/javaa.2012.3258.3261
  • 8. Kizilay Z, Aktas S, Kahraman Cetin N, Kilic MA, Ozturk H. Effect of Tarantula cubensis extract (Theranekron) on peripheral nerve healing in an experimental sciatic nerve injury model in rats. Turk Neurosurg 2019; 29(5): 743-749. doi:10.5137/1019-5149.JTN.26162-19.2
  • 9. Gül Satar NY, Cangül IT, Topal A, Kurt H, Ipek V, Onel GI. The effects of Tarantula cubensis venom on open wound healing in rats. J Wound Care 2017; 26(2): 66-71. doi:10.12968/jowc.2017.26.2.66
  • 10. Oryan A, Moshiri A, Raayat AR. Novel application of Theranekron® enhanced the structural and functional performance of the tenotomized tendon in rabbits. Cells Tissues Organs 2012; 196(5): 442-455. doi:10.1159/000337860
  • 11. Oluwabunmi I, Abiola T. Gastroprotective effect of methanolic extract of Gomphrena celosioides on indomethacin induced gastric ulcer in Wistar albino rats. Int J Appl Basic Med Res 2015; 5(1): 41. doi:10.4103/2229-516x.149238
  • 12. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193(1): 265-275. doi:10.1016/0922-338X(96)89160-4
  • 13. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005; 38(12): 1103-1111. doi:10.1016/j.clinbiochem.2005.08.008
  • 14. Lichtenberger LM. The Hydrophobic Barrier Properties of Gastrointestinal Mucus. Annu Rev Physiol 1995; 57(1): 565-583. doi:10.1146/annurev.ph.57.030195.003025
  • 15. Takeuchi K. Prostaglandin EP Receptors and Their Roles in Mucosal Protection and Ulcer Healing in the Gastrointestinal Tract. Adv Clin Chem 2010; 51(C): 121-144. doi:10.1016/S0065-2423(10)51005-9
  • 16. Utsumi H, Yasukawa K, Soeda T, et al. Noninvasive mapping of reactive oxygen species by in vivo electron spin resonance spectroscopy in indomethacin-induced gastric ulcers in rats. J Pharmacol Exp Ther 2006; 317(1): 228-235. doi:10.1124/jpet.105.095166
  • 17. Ghiselli A, Serafini M, Natella F, Scaccini C. Total antioxidant capacity as a tool to assess redox status: Critical view and experimental data. Free Radic Biol Med 2000; 29(11): 1106-1114. doi:10.1016/S0891-5849(00)00394-4
  • 18. Abdel-Raheem IT. Gastroprotective effect of rutin against indomethacin-induced ulcers in rats. Basic Clin Pharmacol Toxicol 2010; 107(3): 742-750. doi:10.1111/j.1742-7843.2010.00568.x
  • 19. Farzaei MH, Abdollahi M, Rahimi R. Role of dietary polyphenols in the management of peptic ulcer. World J Gastroenterol 2015; 21(21): 6499-6517. doi:10.3748/wjg.v21.i21.6499
  • 20. Chattopadhyay S, Adhikary B, Yadav SK, Roy K, Bandyopadhyay SK. Black tea and theaflavins assist healing of indomethacin-induced gastric ulceration in mice by antioxidative action. Evidence-based Complement Altern Med 2011; 2011: 546560. doi:10.1155/2011/546560
  • 21. Taira K, Watanabe T, Tanigawa T, et al. Roles of cyclooxygenase-2 and prostaglandin E receptors in gastric mucosal defense in Helicobacter pylori-infected mice. Inflammopharmacology 2007; 15(3): 132-138. doi:10.1007/s10787-006-1561-1
  • 22. Takeuchi K. Pathogenesis of NSAID-induced gastric damage: Importance of cyclooxygenase inhibition and gastric hypermotility. World J Gastroenterol 2012; 18(18): 2147-2160. doi:10.3748/wjg.v18.i18.2147
  • 23. Bertrand V, Guessous F, Le Roy AL, et al. Copper-indomethacinate associated with zwitterionic phospholipids prevents enteropathy in rats: Effect on inducible no synthase. Dig Dis Sci 1999; 44(5): 991-999. doi:10.1023/A:1026668816189
  • 24. Abood WN, Abdulla MA, Ismail S. Involvement of inflammatory mediators in the gastroprotective action of Phaleria macrocarpa against ethanol-induced gastric ulcer. World Appl Sci J 2014; 30(30 A): 344-350. doi:10.5829/idosi.wasj.2014.30.icmrp.48
  • 25. Wallace JL. Nitric oxide in the gastrointestinal tract: opportunities for drug development. Br J Pharmacol 2019; 176(2): 147-154. doi:10.1111/bph.14527
  • 26. El-Ela FIA, Farghali AA, Mahmoud RK, Mohamed NA, Moaty SAA. New Approach in Ulcer Prevention and Wound Healing Treatment using Doxycycline and Amoxicillin/LDH Nanocomposites. Sci Rep 2019; 9(1): 6418. doi:10.1038/s41598-019-42842-2

Ayrıntılar

Birincil Dil İngilizce
Konular Genel ve Dahili Tıp
Bölüm Araştırma Makalesi
Yazarlar

Fatma Nihan CANKARA (Sorumlu Yazar)
Suleyman Demirel University Faculty of Medicine
0000-0002-2367-6412
Türkiye


Özlem ÖZMEN
MEHMET AKIF ERSOY UNIVERSITY, FACULTY OF VETERINARY
0000-0002-1835-1082
Türkiye


Hasan Basri SAVAŞ
ALANYA ALAADDIN KEYKUBAT UNIVERSITY, FACULTY OF MEDICINE
0000-0001-8759-4507
Türkiye


Yasemin ŞAHİN
Suleyman Demirel University Faculty of Medicine
0000-0003-4226-674X
Türkiye


Caner GÜNAYDIN
Ondokuz Mayıs University Faculty of Medicine
0000-0002-8304-832X
Türkiye

Yayımlanma Tarihi 29 Ekim 2020
Başvuru Tarihi 22 Eylül 2020
Kabul Tarihi 4 Ekim 2020
Yayınlandığı Sayı Yıl 2020, Cilt 4, Sayı 3

Kaynak Göster

Vancouver Cankara F. N. , Özmen Ö. , Savaş H. B. , Şahin Y. , Günaydın C. Gastroprotective effect of tarantula cubensis extract in the indomethacin-induced peptic ulcer model in rats. Acta Medica Alanya. 2020; 4(3): 278-284.

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