Eksperimental kolit modelinde appendektominin erken dönemde inflamasyon ve oksidatif stres üzerindeki etkileri

Amaç: Appendektominin ülseratif kolit (ÜK) gelişimini engelleyen bir faktör olduğu farklı ülkelerde yapılan olgu-kontrollü çalışmalarda bildirilmiş olup bu etkisinin mukozal immun yanıtta meydana getirdiği değişikliklere bağlı olduğu düşünülmektedir.Çalışmamızın amacı deneysel kolit modelinde appendektominin erken dönemde histopatolojik aktivite ve doku oksidatif stres belirteçleri üzerindeki etkisini araştırmak olmuştur. Yöntem: Otuz adet, ağırlıkları 120-160 g arasında değişen, genç erişkin, dişi Wistar albino sıçanları üç eşit gruba ayrıldı. Tüm gruplara eş zamanlı laparotomi uygulandı. Grup 1: Sham laparotomi (Kontrol grubu); Grup 2: Laparotomi + eş zamanlı appendektomi + iki hafta sonra %4’lük asetik asit ile kolit oluşturulması (Appendektomi + kolit grubu); Grup 3: Sham laparotomi + iki hafta sonra %4’lük asetik asit ile kolit oluşturulması (Kolit grubu). Tüm sıçanlar üçüncü haftanın sonunda eş zamanlı olarak derin eter anestezisi altında kardiak ponksiyon yapılarak sakrifiye edildiler. Daha sonra splenik fleksuraya kadar çıkarılan kolonlarda histopatolojik inflamasyon derinliği ve doku malondialdehid (MDA), süperoksid dismutaz (SOD), glutatyon (GSH) düzeyleri belirlendi. Gruplar arası ortalamaların farkları oneway Anova ve Bonferroni testleri ile belirlendi.Bulgular: Grup 1 ile kolit oluşturulan her iki grup arasında (2 ve 3) histolojik aktivite, MDA, SOD ve GSH düzeyleri arasında istatistiksel anlamlı farklılık saptandı (tüm parametreler için; p=0.000). Ortalama MDA, SOD, GSH düzeyleri grup 1’de sırasıyla, 0.215 nmol/mg.protein, 1.42 U/mg.protein, 20.23 µg/mg.protein; grup 2’de sırasıyla, 0.4013 nmol/mg.protein, 0.8250 U/mg.protein, 9.775 µg/mg.protein; grup 3’de sırasıyla, 0.4556 nmol/mg.protein, 0.6222 U/mg.protein, 6.76 µg/mg.protein olarak saptandı. Grup 2 ve 3 arasında histopatolojik aktivitede anlamlı fark saptanmazken appendektomi uygulanan grupta uygulanmayan gruba oranla lipid peroksidasyonunun son ürünü olan MDA anlamlı daha düşük (p=0.000), antioksidan SOD ve GSH ise anlamlı olarak daha yüksek saptandı (sırasıyla p=0.013 ve p=0.011).Sonuç: Çalışmamızda akut kolit modelinde appendektominin erken dönemde histolojik hasar üzerinde olumlu etkisi gözlenmemiş olmakla birlikte doku düzeyinde oksidatif stres üzerinde anlamlı olumlu etkileri gözlenmiştir. Appendektominin histolojik düzeyde de etkilerinin değerlendirilebilmesi amacıyla uzun süreli, kronik kolit modelleri oluşturulması gerektiğini düşünmekteyiz.

The impact of appendectomy in short term on inflammation and oxidative stress in an experimental colitis model

Objectives: It was reported in recent case-control studies from different countries that appendectomy was a protective factor against the development of ulcerative colitis (UC), and this effect was linked to altered mucosal immune response following appendectomy.The aim of our study was to assess the effects of appendectomy on histopathological activity and tissue oxidative stress markers in an experimantal colitis model.Methods: Thirty female Wistar albino rats, weighing between 120-160 g were divided into three equal groups: Laparotomy simultaneously was performed in all groups. Group 1: Sham laparotomy (Control group); Group 2: Laparotomy + simultaneous appendectomy + colitis induction with 4% acetic acid after two weeks (appendectomy + colitis group); Group 3: Sham laparotomy + colitis induction with 4% acetic acid after two weeks (colitis group). All the animals were sacrified at the end of the third week under deep ether anesthesia via cardiac puncture. Histopathological activity, tissue malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were then assessed in resected colon specimens. Differences between means in different groups were tested with oneway Anova ve Bonferroni tests. Results: Significant differences were noted regarding histological activity, MDA, SOD, and GSH levels between group 1 and both the other groups with colitis (2 and 3) (p=0.000 for all parameters). Mean MDA, SOD, GSH levels were 0.215 nmol/mg.protein, 1.42 U/mg.protein, 20.23 µg/mg.protein in group 1; 0.4013 nmol/mg.protein, 0.8250 U/mg.protein, 9.775 µg/mg.protein in group 2; 0.4556 nmol/mg.protein, 0.6222 U/mg.protein, 6.76 µg/mg.protein in group 3, respectively. No significant difference was noted regarding histological activity between group 2 and 3, but in appendectomized rats (group 2) MDA, the final product of lipid peroxidation was significantly lower (p=0.000), and levels of antioxidants SOD and GSH were significantly higher compared to group 3 (p=0.013 and p=0.011 for SOD and GSH, respectively).Conclusion: A favourable effect of appendectomy on tissue oxidative stress markers was observed in our colitis model whereas this was not the case regarding histopathological activity. We suggest that chronic colitis models with longer follow-up periods should be planned in order to assess whether this favourable effect of appendectomy on tissue oxidative stress might be observed on histopathological inflammation as well.

___

  • 1. Jewell DP. Ulcerative colitis. In: Feldman M, Scharschmidt BF, Sleisenger MH, eds. Sleisenger and Fordtran’s Gastrointestinal and Liver Diseases. 5th ed. Vol. 2. Philadelphia: J.B. Lippincott; 1993. p. 1305-1330.
  • 2. Lashner B.A. Epidemiology of inflammatory bowel disease. Gastroenterol Clin North Am 1995; 24: 467-474.
  • 3. Barkin JS, Green JA. Inflammatory bowel disease: medical management. In: Berk JE, Haubrich WS, Kalser MH, Roth JLA, Shaffner F, eds. Bockus Gastroenterology. 5th ed. Vol. 2. Philadelphia: J.B. Lippincott; 1994. p. 1374-1381.
  • 4. Farmer RG, Easley KA, Farmer JM. Assessing quality of life for patients with inflam- matory bowel disease. Cleve Clin J Med 1992; 58: 7-15.
  • 5. Kirsner JB. Overview of etiology, pathogenesis, and epidemiology of inflammatory bowel disease. In: Berk JE, Haubrich WS, Kalser MH, Roth JLA, Schaffner F, eds. Bockus Gastroenterology. 5th ed. Vol. 2. Philadelphia: J.B.Lippincott; 1994. p. 1293-1318.
  • 6. Sutherland RL, May GR, Shaffer EA. Sulfasalazine revisited: a meta-analysis of 5-aminosalicyclic acid in the treatment of ulcerative colitis. Ann Int Med 1993; 118: 640-649.
  • 7. Podolsky DK. Inflammatory bowel disease. N Engl J Med 1991; 325: 928.
  • 8. Fiocchi C. Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology 1998; 115: 182-205.
  • 9. Lowenfels AB. Appendectomy and ulcerative colitis. Gastroenterology 1994; 107: 1570.
  • 10. Russel MG, Dorant E, Brummer RJ, et al. Appendectomy and the risk of developing ulcerative colitis or Crohn's disease: Results of a large case-control study. South Limburg Inflammatory Bowel Disease Study Group. Gastroenterology 1997; 113: 377-382.
  • 11. Koutroubakis IE, Vlachonikolis IG. Appendectomy and the development of ulcerative colitis: results of a metaanalysis of published case-control studies. Am J Gastroenterol 2000; 95: 171-176.
  • 12. Fiocchi C. Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology 1998; 115: 182-205.
  • 13. Gilat T, Hacohen D, Lilos P, Langman MJ. Childhood factors in ulcerative colitis and Crohn’s disease. An international cooperative study. Scand J Gastroenterol 1987; 22: 1009-1024.
  • 14. Rutgeerts P, D’Haens G, Hiele M, Geboes K, Vantrappen G. Appendectomy protects against ulcerative colitis. Gastroenterology 1994; 106: 1251-1253.
  • 15. Lowenfels AB. Appendectomy and ulcerative colitis. Gastroenterology 1994; 107: 1570-1572.
  • 16. Minocha A, Raczkowski CA. Role of appendectomy and tonsillectomy in pathogenesis of ulcerative colitis. Dig Dis Sci 1997; 42: 1567-1569.
  • 17. Duggan AE, Usmani I, Neal KR, et al. Appendectomy, chilhood hygiene, Helicobacter pylori status and risk of inflammatory bowel disease: a case control study. Gut 1998; 43: 494-498.
  • 18. Reif S, Lavy A, Keter D, et al. Appendectomy is more frequent but not a risk factor in Crohn’s disease while being protective in ulcerative colitis: a comparison of surgical procedures in inflammatory bowel disease. Am J Gastroenterol 2001; 96: 829-832.
  • 19. Naganuma M, Iizuka B, Torii A, et al. Appendectomy protects against the development of ulcerative colitis and reduces its recurrence: results of a multicenter case-controlled study in Japan. Am J Gastroenterol 2001; 96: 1123-1126.
  • 20. Russel MG, Dorant E, Brummer RJ, et al. Appendectomy and the risk of developing ulcerative colitis or Crohn’s disease: results of a large case-control study. Gastroenterology 1997; 113: 377-382.
  • 21. Dasso JF, Howell MD. Neonatal appendectomy impairs mucosal immunity in rabbits. Cell Immunol 1997; 182: 29-37.
  • 22. Mizoguchi A, Mizoguchi E, Chiba C, Bhan AK. Role of appendix in the development of inflammatory bowel disease in TCR-alpha mutant mice. J Exp Med 1996; 184: 707-715.
  • 23. Andersson RE, Olaison G, Tysk C, Ekbom A. Appendectomy and protection against ulcerative colitis. N Engl J Med 2001; 344: 808-814.
  • 24. Andersson RE, Lambe M. Incidence of appendicitis during pregnancy. Int J Epidemiol 2001; 30: 1281-1285.
  • 25. Krieglstein CF, Cerwinka WH, Laroux FS, et al. Role of appendix and spleen in experimental colitis. J Surg Res 2001; 101: 166-175.