The effects of caffeic acid phenethyl ester (CAPE) on acetic acid induced colitis in rats

Kafeik asit fenetil ester (KAPE), iskemi-reperfüzyon ve toksik hasarda oksidatif stres yoluyla ortaya çıkan reaktif oksijen ürünlerinden dokuyu koruyan, propolis ekstresinin aktif bir komponentidir. İnflamatuar barsak hastalığının (İBH) patogenezinde anormal oksidatif metabolizma önemli olduğundan, İBH’da serbest radikallerin rolü üzerine dikkat çekilmiştir. Bu çalışmanın amacı ratlarda asetik asitin (AA) neden olduğu kolitte KAPE’nin antioksidan parametrelere ve kolit gelişimi üzerine etkilerin değerlendirmektir. 21 adet 150-200 g ağırlığında Wistaralbino dişi rat kullanıldı. Ratlar rastgele 3 gruba ayrıldı: sırasıyla kontrol grubu (6), kolit grubu (8) ve KAPE grubu (7). %4’lük AA kolon içine lavmanla verilerek kolit oluşturuldu. AA lavmanıyla kolit oluşturulduktan sonra 3 gün süreyle KAPE verilerek kolit üzerine KAPE’nin sonrak etkileri değerlendirildi. Kolit grubunda artmış olan kolonik malondialdehit ve nitrik oksit düzeyi KAPE tedavisiyle (10 µmol/kg) azaldı (sırasıyla p=0.043, p=0.006). Kolit grubunda azalmış olan glutatyon aktivitesi KAPE tedavisiyle arttı (p=0.008). KAPE makroskobik olarak kolit grubunun lezyon skorunda azalmaya neden olmadı (p>0.05). Bizim verilerimiz KAPE tedavisinin biyokimyasal parametrelerde pozitif etkisini gösterirken, istatistiksel olarak anlamlı bir histolojik iyileşme oluşturmadığını göstermiştir. KAPE, antioksidan ve antiinflamatuar etkileriyle ratlarda AA ile oluşturulan kolit modelinde yararlı gibi görünmektedir. Biz daha uzun süreli ve daha yüksek doz KAPE ile yapılan ilave, daha anlaşılır deneysel çalışmalarla KAPE’nin etkilerinin değerlendirilmes gerektiğine inanıyoruz.

Kafeik asit fenetil esterin ratlarda asetik asitle indüklenmiş kolite etkileri

Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, protects tissues from reactive oxygene species mediated oxidative stress in ischemia-reperfusion and toxic injuries. Since abnormal oxidative metabolism is important in the pathogenesis of inflammatory bowel disease (IBD), increased attention has been focused on the role of free radicals in IBD. The aim of this study was to investigate the effect of CAPE on the development of colitis and antioxidant parameters of rats subjected to acetic acid (AA) induced colitis. Twenty one female Wistar-albino rats weighing 150-200 g were used. The rats were randomly divided into three groups: control group (n=6), colitis group (n=8), CAPE group (n=7), respectively. Colitis was induced by intracolonic enema with 4% AA. Colitis was induced using an enema of AA following which CAPE was administrated for 3 days to induce colitis and effect of CAPE was subsequently evaluated. The increase in colonic malondialdehyde and nitric oxide level at the colitis group was reduced by CAPE (10 µmol/kg) treatment (p=0.043, p=0.006, respectively). Reduced glutathione activity in the colitis group was increased by CAPE treatment (p=0.008). Treatment with CAPE did not reduce the lesion score of the colitis group at macroscopic level (p>0.05). Our data showed its positive effects on biochemical parameters, although there was not statistically significant histologic improvement with CAPE tratment. CAPE seemed to be beneficial in an AA-induced rat colitis model through the antioxidant and anti-inflammatory effect. We believe further studies such as longer CAPE treatment and higher dosages are needed to investigate the effects of CAPE more clearly in experimental colitis.

Kaynakça

1. Takaki K, Mitsuyama K, Tsuruta O, Toyonaga A and Sata M. Attenuation of experimental colonic injury by thiazolidinedione Agents. Inflamm Res 2006;55: 10–15.

2. Grisham MB. Oxidant and free radicals in inflammatory bowel disease. Lancet 1994;344: 859-61.

3. Fiocchi C. Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology 1998;115: 182-205.

4. Colon AL, Menchen LA, Hurtado O, De Cristobal J, Lizasoain I, Leza JC, et al. Implication of TNF-alpha convertase (TACE/ADAM) in inducible nitric oxide synthase expression and inflammation in an experimental model of colitis. Cytokine 2001;16: 220–6.

5. Grisham MB, McCord JM. Chemistry and cytotoxicity of reactive oxygen metabolites. In: Taylor AE, Matalon S, Ward PA (eds) Physiology of oxygen radicals. Williams and Wilkins, Baltimore pp 1986; 1–18.

6. Williams JG, Hughes LE, Hallett MB. Toxic oxygen metabolite production by circulating phagocytic cells in inflammatory bowel disease. Gut 1990;31: 187–93.

7. Grisham MB, Gaginella TS, von Ritter C, Tamai H, Be RM, Granger DN. Effects of neutrophil-derived oxidants on intestinal permeability, electrolyte transport, and epithelial cell viability. Inflammation 1990;14: 531–42.

8. Ilhan A, Koltuksuz U, Ozen S, Uz E, Ciralik H, Akyol O. The effects of caffeic acid phenethyl ester (CAPE) on spinal cord ischemia/reperfusion injury in rabbits. Eur J Cardiothorac Surg 1999;16: 458–63.

9. Russo A, Longo R, Vanella A. Antioxidant activity of propolis: role of caffeic acid phenethyl ester and galangin. Fitoterapia 2002;73: 21–9.

10. Sud’ina GF, Mirzoeva OK, Puskareva MA, Korshunova GA, Sumbatyan NV, Varfolomeev SD. Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties. FEBS Lett 1993;329: 21–4.

11. Cicala C, Morello S, Iorio C, Capasso R, Borrelli F, Mascolo N. Vascular effects of caffeic acid phenethyl ester (CAPE) on isolated rat thoracic aorta. Life Sci 2003;73: 73–80.

12. Fitzpatrick LR, Wang J, Le T. Caffeic acid phenethyl ester, an inhibitor of nuclear factor-kappa B, attenuates bacterial peptidoglycan polysaccharide-induced colitis in rats. J Pharmacol Exp Ther 2001;299: 915–20.

13. Su ZZ, Grunberger D, Fisher PB. Suppression of adenovirus type 5 EIA-mediated transformation and expression of the transformed phenotype by caffeic acid phenethyl ester (CAPE). Mol Carcinogen 1991;4: 231–42.

14. Marquez N, Sancho R, Macho A, Calzado MA, Fiebich BL, Munoz E. Caffeic acid phenethyl ester inhibits T-cell activation by targeting both nuclear factor of activated T-cells and NF-kappa B transcription factors. J Pharmacol Exp Ther 2004;308: 993–1001.

15. Ozer MK, Parlakpınar H, Acet A. Reduction of ischemia reperfusion induced myocardial infarct size in rats by caffeic acid phenethyl ester (CAPE). Clin Biochem 2004;37: 702–5.

16. Ozguner F, Oktem F, Ayata A, Koyu A, Yılmaz HR. A novel antioxidant agent caffeic acid phenethyl ester prevents long-term mobile phone exposure-induced renal impairment in rat. Mol Cell Biochem 2005;277: 73–80.

17. Grunberger D, Banerjee R, Eisinger K, Oltz EM, Efros L, Caldwell M, et al. Preferential cytotoxicity on tumor cells by caffeic acid phenethyl ester isolated from propolis. Experientia 1998;44: 230-2.

18. Siegmund B, Lehr HA, Fantuzzi G, Dinarello CA. IL-1-converting enzyme (caspase-1) in intestinal inflammation. Proc Natl Acad Sci 2001;98: 13249-54.

19. Buege JA, Aust SD. Lactoperroxidase catalysed lipid peroxidation of microsomal and artificial membranes. Biochem Biophys Acta 1976;444: 192–201.

20. Durak I, Yurtarslanı Z, Canbolat O, Akyol O. A methodological approach to superoxide dismutase (SOD) activity assay based on inhibition of nitroblue tetrazolium (NBT) reduction. Clin Chim Acta 1993;214: 103–4.

21. Oktem F, Ozguner F, Sulak O, Olgar Ş, Akturk O, Yılmaz HR, Altuntas I. Lithium-induced renal toxicity in rats: protection by a novel antioxidant caffeic acid phenethyl ester. Molecular and Cellular Biochemistry 2005;277: 109–5.

22. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967;70: 158–69.

23. Aebi H. Catalase. In: Bergmeyer U. (Ed.), methods of enzymatic analysis. Academic Pres pp. 1974;673–7.

24. Cortas NK, Wakid NW. Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. Clin Chem 1990;36: 1440–3.

25. Ek RO, Serter M, Ergin K, Yildiz Y, Cecen S, Kavak T, et al. The Effects of caffeic acid phenethyl ester (CAPE) on TNBS-induced colitis in ovariectomized rats. Dig Dis Sci 2007;1007:1609-17.

26. Yıldız Y, Serter M, Ek RO, Ergin K, Cecen S, Demir EM, Yenisey Ç. Protective effects of caffeic acid phenethyl ester on intestinal ischemiareperfusion injury. Dig Dis Sci 2009;54: 738-44.

27. Fitzpatrick LR, Wang J, Le Truc. Caffeic Acid Phenethyl Ester, an Inhibitor of Nuclear Factor-κB, Attenuates Bacterial Peptidoglycan Polysaccharide-Induced Colitis in Rats. The Journal of Pharmacology and Experimental Therapeutics 2001;299: 915-20.

28. Girgin F, Karaoglu O, Erkus M, Tuzun S, Ozutemiz O, Dincer C, et al. Effects of trimetazidine on oxidant/ antioxidant status in trinitrobenzenesulfonic acid-induced chronic colitis. J Toxicol Environ Health A 2000;59: 641–52.

29. Verspaget HW, Pena AS, Weterman IT, Lamers C. Diminished neutrophil function in Crohn’s disease and ulcerative colitis identified by decreased oxidative metabolism and low superoxide dismutase content. Gut 1988;29: 223–8.

30. Harputluoğlu MM, Demirel U, Neslihan Y, Karadağ N, Temel İ, Fırat S, et al. The effects of Gingko biloba extract on acetic acid induced colitis in rats. Turk J Gastroenterol 2006;17: 177-82.

31. Kurutas EB, Cetinkaya A, Bulbuloglu E, Kantarceken B. Effects of antioxidant therapy on leukocyte myeloperoxidase and cu/zn-superoxide dismutase and plasma malondialdehyde levels in experimental colitis. Mediators of İnflammation 2005;6: 390–4.

32. Kolios G, Valatas V, Ward SG. Nitric oxide in inflammatory bowel disease: a universal messenger in an unsolved puzzle. Immunology 2004;113: 427–37.

33. Reinders CI, Herulf M, Ljung T, Hollenberg J, Weitzberg E, Lundberg JO, et al. Rectal mucosal nitric oxide in differentiation of inflammatory bowel disease and irritable bowel syndrome. Clin Gastroenterol Hepatol 2005;3: 777–83.

34. Nieto N, Torres MI, Fernandez MI, Giron MD, Rios A, Suarez MD, et al. Experimental ulcerative colitis impairs antioxidant defense system in rat intestine. Dig Dis Sci 2000;45: 1820–7.

35. Kuralay F, Yildiz C, Ozutemiz O, Islekel H, Caliskan S, Bingol B, et al. Effects of trimetazidine on acetic acid-induced colitis in female Swiss rats. J Toxicol Environ Health 2003;66: 169–9.

36. Kruidenier L, Kuiper I, van Duijn W, Marklund SL, van Hogezand RA, Lamers CB, et al. Differential mucosal expression of three superoxide dismutase isoforms in inflammatory bowel disease. J Pathol 2003;201: 7–16.

37. Jourd’heuil D, Morise Z, Conner EM, Grisham MB. Oxidants, transcription factors, and intestinal inflammation. J Clin Gastroenterol 1997;25: 61-72.

38. Banan A, Fields JZ, Zhang Y, Keshavarzian A. iNOS upregulation mediates oxidant-induced disruption of F-actin and barrier of intestinal monolayers. Am J Physiol Gastrointest Liver Physiol 2001;280: 1234-6.

39. McKenzie SJ, Baker MS, Buffington GD, Doe WF. Evidence of oxidant-induced injury to epithelial cells during inflammatory bowel disease. J Clin Invest 1996;98: 136–41.

40. Millar AD, Rampton DS, Chander CL, Claxson AW, Blades S, Coumbe A, et al. Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis. Gut 1996;39: 407-15.

41. Deng CH, Xia B, Chen DJ, Zhou Y, Gong TT, Guao ZQ. The mucosa protective effects of superoxide dismutase on rats colitis induced by acetic acid. Zhongguo Bingli Shengli Zazhi 1994; 10: 23-5.

42. Schroder O, Stein J. Low dose methotrexate in inflammatory bowel disease: current status and future directions. Am J Gastroenterol 2003;98: 530-7.

43. Nosal’ova V, Cerna S, Bauer V. Effect of N-acetylcysteine on colitis induced by acetic acid in rats. General Pharm 2000;35: 77-81.

44. Kaya E, Gur ES, Ozguc H, Tokyay R. L-Glutamine enemas attenuate mucosal injury in experimental colitis. Dis Colon Rectum 1999;42: 1209-15.

45. Simmonds NJ, Millar AD, Blake DR, Rampton DS. Antioxidant effects of aminosalicylates and potential new drugs for inflammatory bowel disease: assessment in cell-free systems and inflamed human colorectal biopsies. Aliment Pharmacol Ther 1999;13: 363–72.

46. Ademoglu E, Erbil Y, Tam B, Barbaros U, Ilhan E, Olgac V, et al. Vitamin E and selenium have beneficial effects on trinitrobenzenesulfonic acid-induced experimental colitis. Dig Dis Sci 1999;49: 102–8.

Kaynak Göster

Yeni Tıp Dergisi
  • ISSN: 1300-2317
  • Yayın Aralığı: Yılda 0 Sayı
  • Başlangıç: 2018

47054

Sayıdaki Diğer Makaleler

"Değişik özür seviyesindeki serebral palsili çocukların annelerinin depresyon düzeyleri farklı mıdır?"

Akmer MUTLU, PELİN PİŞTAV AKMEŞE, Mintaze Kerem GÜNEL

Bir huzurevinde kalan yaşlıların yalnızlık düzeylerinin incelenmesi

FEYZA DERELİ, Bennur KOCA, SACİDE DEMİRCAN, Neslihan TOR

Side effects of metoclopramide: Does it deserve to prescribe for nausea, vomiting?

Hızel Selda BÜLBÜL, Dibek Emine MISIRLIOĞLU, Erennur TUFAN, Olcay EVLİYAOĞLU

Postmenopozal hormon tedavisi kardiyovasküler hastalık riskini azaltıyor mu?

Nilgün Öztürk TURHAN, Serap SİMAVLI, İlknur İnegöl GÜMÜŞ

Single dose repaglinide has no acute effect on platelet aggregation in newly diagnosed type 2 diabetes mellitus patients

Engin Deniz GÖK, Oral NEVRUZ, Mehmet YOKUŞOĞLU, Cengiz BEYAN, Mahmut YAZICI, Mustafa KUTLU

Posterior sirkülasyon infarktında baziler arter dolikoektazisinin MRG ile değerlendirilmesi

Bahri KEYİK, Gököen Çoban ŞAHİN, Bahar YANIK, Baki HEKİMOĞLU

Sol omuzda nodüler melanom, amelanotik melanom ve yüzeyel yayılan malign melanom birlikteliği olan bir olgu sunumu

Zeynep TÜRKŞEN, Ömer Faruk TANER, Ayla TEZER, AYŞE SERAP KARADAĞ, Fatih TEKİN

Proteomik

SEVİL KURBAN, İdris MEHMETOĞLU

Pigmented villonodular synovitis of shoulder; radiologic assessment with MRI findings

HASAN MURAT AYDIN, Nilay Aydın OKTAY, Hüsamettin SARGIN, Baki HEKİMOĞLU

Aynı cerrahi seansta sezaryen sonrası laparoskopik kolesistektomi

Önder SÜRGİT, Zeynep KAMALAK, İlknur İnegöl GÜMÜŞ, Nilgün Öztürk TURHAN