Journals / Kolon ve Rektum Hastalıkları Dergisi / 2010 / Cilt: 20 - Sayı: 2

2,4,6 trinitrobenzensulfonik asid (TNBSA) İle indüklenmiş deneysel kolit modelinde düşük doz metotreksat'ın endotelial disfonksiyon ve programmlanmış hücre ölümü (apoptosis) üzerine etkileri

The effects of low-dose methotrexate on endothelial dysfunction and programmed cell death (apoptosis) in 2,4,6 Trinitrobenzensulphonic acid (TNBSA) induced model of experimental colitis

Pages
66–75
Publication Date
2022-10-18
DOI
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

CONCLUSION: In conclusion; Mtx may be suggested as an alternate agent especially in acute attack episodes of inflammatory bowel disease.

📌 3 Key Takeaways

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Objective & Hypothesis:OBJECTIVE: Currently, the medical investigations on alternative drug therapies in inflammatory bowel disease (IBD) have been increased.
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Key Findings & Data:METHODS: This study was carried out on 36 rats induced for colitis by 2,4,6 trinitrobenzensulfonic (TNBS) acid, and they were divided into 3 groups: Group I: TNBS+Mtx, Group II: TNBS, Group III: saline enema.
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Conclusion & Impact:CONCLUSION: In conclusion; Mtx may be suggested as an alternate agent especially in acute attack episodes of inflammatory bowel disease.
🔬Design:Modeling & Simulation
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters

Abstract

OBJECTIVE: Currently, the medical investigations on alternative drug therapies in inflammatory bowel disease (IBD) have been increased. Methotrexate (Mtx) has been used in the management of IBD due to its anti-inflammatory effects. It’s aimed to investigate the effects of Mtx on endothelial dysfunction and colonic mucosa in experimental acute colitis. METHODS: This study was carried out on 36 rats induced for colitis by 2,4,6 trinitrobenzensulfonic (TNBS) acid, and they were divided into 3 groups: Group I: TNBS+Mtx, Group II: TNBS, Group III: saline enema. While single dose of Mtx administered as an intramuscular injection in drug group (Group I), only colitis was induced in the second group (Group II). 1 ml/kg/daily of saline enema was administered intrarectally to the third group.On the seventh day of the experiment, animals were sacrificed and then distal colons were removed surgically for immunohistochemical and biochemical analyses. Colonic mucosal NO, iNOS, eNOS, MPO activity, macroscopic changes and histomorphology were evaluated.RESULTS: Mtx reduced MPO activity, TNF-α, NO, iNOS and eNOS releases from inflamed colonic tissue and healed mucosal damage in experimental model of acute colitis.Additionally, Mtx suppressed apoptotic and proliferative processes in inflamed colonic tissue. CONCLUSION: In conclusion; Mtx may be suggested as an alternate agent especially in acute attack episodes of inflammatory bowel disease.

Özet

AMAÇ: Günümüzde iltihabi barsak hastalıkları (İBH) için yürütülen farklı ilaç tedavileri üzerine yapılan çalışmalar giderek artmaktadır.Metotreksat (Mtx) antienflamatuar etkileri nedeniyle İBH’nın tedavisinde kullanılmakta olan bir ilaçtır. Bu çalışmada MTX’in deneysel kolit modelinde endothelial disfonksiyon ve kolon mukozası üzerine etkilerinin araştırılması amaçlanmıştır. YÖNTEMLER: Bu çalışma, 2,4,6 trinitrobenzensulfonik asit (TNBS) ile indüklenmiş kolitli 36 sıçan üzerinde gerçekleştirildi. Denekler 3 gruba ayrıldı: Grup I: TNBS+Mtx, Grup II: TNBS ve Grup III: Serum fizyolojik lavman. Grup I’e tek doz Mtx uygulanırken, Grup II’de sadece kolit oluşturuldu. III.gruba ise 1 ml/kg/gün serum fizyolojik lavman uygulandı.Deneyin yedinci günü denekler feda edilerek distal kolon kısımları immunohistokimyasal ve biyokimyasal analizler için çıkartıldı. BULGULAR: Bu deneysel akut kolit modelinde Mtx, yangılı kolon mukozasındaki MPO aktivitesi, TNF-α, NO, iNOS ve eNOS salınımını azaltmış ve mukozal hasarı iyileştirmiştir. Bunun yanında Mtx uygulanımı ile apoptotik ve proliferatif süreç baskılanmıştır. SONUÇ: Mtx özellikle iltihabi barsak hastalığının akut alevlenme dönemlerinde alternatif bir ilaç olarak düşünülebilir.

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Cite This Article

VATANSEVER, S., SAKARYA, A., KARA, E., VAR, A. (2022). 2,4,6 trinitrobenzensulfonik asid (TNBSA) İle indüklenmiş deneysel kolit modelinde düşük doz metotreksat'ın endotelial disfonksiyon ve programmlanmış hücre ölümü (apoptosis) üzerine etkileri. Kolon ve Rektum Hastalıkları Dergisi, Cilt: 20 - Sayı: 2, 66–75. https://ajindex.com/articles/575392

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References (18)

  1. Asano K, Chee CBE, Gaston B, et al. Constitutive and inducible nitric oxide synthase gene expression regulation and activity in human lung epithelial cells. Proct Natl Acad Sci USA 1994;91:10089-93
  2. Aslan M, Ryan TM, Adler B, et al. Oxygen radical inhibition of nitric oxide-dependent vascular function in sickle cell disease. Proc Natl Acad Sci USA 2001;98:15215-20
  3. Boughton-Smith NK, Evans SM, Hawkey CJ. Nitric oxide synthase activity in ulcerative colitis and Crohn's disease. Lancet 1993;342:338-40
  4. Cortas NK, Wakid VW. Determination of inorganic nitrate in serum and urine by a kinetic cadmiumreduction method. Clin Chem 1990;36:1440-43
  5. Cross RK, Wilson KT. Nitric oxide in inflammatory bowel disease. Inflamm Bowel Dis 2003; 9:179-89
  6. Dijkhorst-Oei LT, Stroes ES, Koomans HA, Rabelink TJ. Acute simultaneous stimulation of nitric oxide and oxygen radicals by angiotensin II in humans in vivo. J Cardiovasc Pharmacol 1999;33:420-24
  7. Drexler H, Hornig B. Endothelial dysfunction in human disease. J Mol Cell Cardiol 1999; 31: 51-60
  8. Egan LJ, Sandborn WJ.Methotrexate for inflammatory bowel disease: Pharmacology and preliminary results. Mayo Clin Proc 1998;71:69-80
  9. Kocaman O, Sahin T, Aygun C, Senturk Ö, Hulagu S. Endothelial dysfunction in patients With ulcerative colitis. Inflamm Bowel Dis 2006;12:166-71
  10. Hengartner MO. The biochemistry of apoptosis. Nature 2000;407:770-76
  11. Sartor RB. Current concepts of the etiology and pathogenesis of ulcerative colitis and Crohn's disease. Gastroenterol Clin North Am 1995;24:475-507
  12. Fiocchi C. Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology 1998;115;182-205
  13. Middleton S, Shorthouse M, Hunter JO. Increased nitric oxide synthesis in ulcerative colitis. Lancet 1993;341:465-66
  14. Luscher TF. Endothelial dysfunction: the role and impact of the reninangiotensin system. Heart 2000;84:20-22
  15. Wei H, Wei L, Frenkel L, Bowen R, Barnes S. Inhibition of tumour promoter-induced hydrogen peroxide formation in vitro and in vivo by genistein. Nutr Cancer 1993;20:1-12
  16. Schröder O. and Stein J. Low dose methotrexate in inflammatory bowel disease: current status and future directions. Am J Gastroenterol 2003;98:530-37
  17. Chong RY, Hanauer SB, Cohen RD. Methotrexate in Crohn's disease. How is it doing? Gastroenterology 1998;114:A951 (abstract)
  18. Feagan BG, Rochon J, Fedorak RN, et al. Methotrexate for the treatment of Crohn's disease. The North American Crohn's Stud