İndometazin İle İndüklenerek Oluşturulan Gastrik Ülsere Karşı Propolisin Etkinliğinin Belirlenmesi

Yıl 2023, Cilt: 6 Sayı: 2, 67 - 73, 01.12.2023

Serap Korkmaz , Zafer Tabur

https://doi.org/10.55257/ethabd.1329373

Öz

İndometazin; indol türevi, non-steroid antienflamatuvar bir ajan olan paraklorobenzoil-metoksi-metilindol-asetik asidin genelde kullanılan ismidir. İndometazin’in antienflamatuvar
etkilerinin yanı sıra, analjezik ve antipiretik etkileri de bulunan kimyasal bir ajan olarak kabul edilmektedir. İndometazin’in olumlu etkileri dikkate alındığında; küçük hücreli olmayan akciğer kanserinin büyümesini baskıladığı, insanlarda meme kanser hücresinin metastaz ve invazyonunu azalttığını söylemek mümkündür. İmmün cevabı geliştirmesinin yanı sıra, apoptotik hücre ölümünü artırdığı yapılan bilimsel çalışmalarla tespit edilmiştir. Son yıllarda özellikle, korona virüs replikasyonunu inhibe etmede, İndometazin’in etkili olduğu görülmüştür. Ayrıca, İndometazin hiperbarik oksijenasyonda görülen konvülsiyonları hafifletir ve hiperemi oluşumunu önlemektedir.
İndometazin’in olumsuz etkileri ele alındığında, bu kimyasal ajanın yanlış dozlanması sonucunda en yaygın olarak gözlenen yan etkisi mide ülseri şeklinde kendini göstermektir. İndometazin’in anti-enflamatuvar etkisinden COX–2, gastrointestinal toksik etkilerinden ise COX–1 enzim inhibisyonu sorumlu tutulmaktadır. İndometazin hem COX–1 hem de COX–2 enzimlerini inhibe ederek, prostaglandin sentezini güçlü bir şekilde engeller. Bu nedenledir ki indometazinin ülser oluşturma oranı diğer nonsteroid antienflamatuvar ilaçlara göre çok daha yüksek olduğundan, deneysel ülser modeli oluşturmak amacı ile daha çok tercih edilmektedir. Oluşturulan bu mide ülseri modelleri tedavisinde kimyasalın yanı sıra bitkisel ve hayvansal ürünlerde yaygın olarak kullanılmaktadır.
“Tıbbi bitkilerin ve hayvansal ürünlerin canlı sistemler üzerinde; sedatif, analjezik, antipiretik, antiülseratif, kardiyoprotektif, antibakteriyel, antifungal ve antiviral gibi birçok etkisi çalışmalarla ortaya konulmuştur.” Bitkiler, serbest radikalleri nötralize ederek, oksidatif stres ve reaktif oksijen türleri ile bağlantılı birçok kronik hastalığın ilerlemesini önlemektedir. Propolisin anti-bakteriyal, anti-fungal ve anti-ülseratif etkilerinden yaygın olarak faydalanıldığı göze alındığında mide ülseri üzerine de düzenli tüketimle olumlu etkileri olabileceği düşünülmektedir.
Bu çalışma ile Propolis’in mide ülseri üzerindeki etkileri teorik olarak ele alınarak ilgili literatüre katkı sağlanması hedeflenmektedir.

Anahtar Kelimeler

Bal arısı, Propolis, İndometazin, Mide ülseri

Determination of the Efficacy of Propolis Against Indomethacin-Induced Gastric Ulcer

Öz

Indomethacin; The indole derivative is the commonly used name of parachlorobenzoyl-methoxy-methylindole-acetic acid, a non-steroidal anti-inflammatory agent. Anti-inflammatory of indomethacin in addition to its effects, it is accepted as a chemical agent with analgesic and antipyretic effects. Considering the positive effects of indomethacin; It is possible to say that it suppresses the growth of non-small cell lung cancer and reduces the metastasis and invasion of breast cancer cells in humans. Also, indomethacin alleviates convulsions seen in hyperbaric oxygenation and prevents hyperemia.
Considering the adverse effects of indomethacin, the most common side effect observed as a result of incorrect dosing of this chemical agent is manifesting itself in the form of gastric ulcer. COX-2 enzyme inhibition is responsible for the anti-inflammatory effect of indomethacin and COX-1 enzyme inhibition for its gastrointestinal toxic effects. For this reason, since the ulcer formation rate of indomethacin is much higher than other nonsteroidal anti-inflammatory drugs, it is more preferred to create an experimental ulcer model. These created gastric ulcer models are widely used in herbal and animal products as well as chemicals in the treatment.
“On living systems of medicinal plants and animal products; Many effects such as sedative, analgesic, antipyretic, anti-ulcerative, cardioprotective, antibacterial, antifungal, and antiviral have been demonstrated in studies. Considering that the anti-bacterial, anti-fungal and anti-ulcerative effects of propolis are widely used, it is thought that it may have positive effects on stomach ulcers with regular consumption. With this study, it is aimed to contribute to the relevant literature by considering the effects of Propolis on stomach ulcers theoretically.

Anahtar Kelimeler

Honeybee, Propolis, Indomethacin, Gastric ulcer

Kaynakça

• Amici, C., Di Caro, A., Ciucci, A., Chioppa, L., Castilletti, C., Martella, V., et al., 2006. Indomethacin has a potent antiviral activity against SARS coronavirus. Antivir Ther, 11: 1021-1030.
• Arthur, C., Guyton, M. D., ve Hall, J. E., 2001. Tıbbi fizyoloji. Nobel Tıp Kitabevi, Türkiye, 185-300.
• Banerjee, S., Hawksby, C., Miller, S., Dahill, S., Beattie, A. D., and McColl, K. E., 1994. Effect of helicobacter pylori and its eradication on gastric juice ascorbic acid. Gut, 35: 317- 322.
• Balcıoğlu, S., 2017. Propolis ve soğan ekstraktlarının antimikrobiyal ve 3T3 fibroblast hücreleri üzerine etkileri. Yüksek Lisans Tezi, Üsküdar Üniversitesi Fen Bilimleri Enstitüsü Moleküler Biyoloji Anabilim Dalı, İstanbul.
• Brandman, S., Vandenburg, M. J., Jenkins, R., and Currie, W. J. C., 1985. The Effect of non-steroidal antiinflammatory therapy on plasma neuropeptide concentrations in patients with osteoarthritis. Brit J Rheumatol, 24: 46-52.
• Brune, K., Dietzel, K., Nurnberg, B., and Schneider, H. T., 1987. Recent insight into the mechanism of gastrointestinal tract ulceration. Scand J Rheumatol Suppl., 65: 135-140.
• Burke, A., Smyth, E., and FitzGerald, G. A., 2006. Analgesic-antipyretic agents; pharmacotherapy of gout. In brunton LL, ed. Goodman&Gilman’s the pharmalogical basis of therapeutics. USA, The McGraw-Hill Companies; 695-96.
• Cao, Y., Pearman, A. T., Zimmerman, G. A., McIntyre, T. M., and Prescott, S. M., 2000. Intracellular unesterified arachidonic acid signals apoptosis. P Natl Acad Sci USA, 97: 11280-11285.
• Connolly, J. M., Liu, X. H., and Rose, D. P., 1996. Dietary linoleic acid-stimulated human breast cancer cell growth and metastasis in nude mice and their suppression by indomethacin, a cyclooxygenase inhibitor. Nutr Cancer, 25: 231-240.
• Coşkun, P., ve İnci, H., 2020. Propolisin kimyasal içeriği ile antibakteriyel, antiviral ve antioksidan aktivitesi. ISPEC Tarım Bilimleri Dergisi 4 (4): 1059.
• Davies, G. R., Simmonds, N. J., Stevens, T. R., Sheaff, M. T., Banatvala, N., Laurenson, I. F., et al., 1994. Helicobacter pylori stimulates antral mucosal reactive oxygen metabolite production in vivo. Gut, 35: 179-185.
• Doğan, N., ve Hayoğlu, İ., 2012. Propolisin kullanım olanakları. Harran Üniversitesi Ziraat Fakültesi Dergisi 16 (3): 39-48.
• Doğanyiğit, Z., Üner, A. K., Okan, A., and Silici, S,. 2021. Protective effect of propolis and bee bread in experimental gastric ulcer model. Mellifera Dergi 21 (1), 18-28.
• El-Moselhy, M. A., Abdel-Hamid, N. M., and Abdel-Raheim, S. R., 2009. Gastroprotective effect of nicorandil in indomethacin and alcohol-induced acute ulcers. Appl Biochem Biotechnol, 152: 449-459.
• Emori, H. W , Paulus, H., Bluestone, R., Champion, G. D., and Pearson, C., 1976. Indomethacin serum concentrations in man - effects of dosage, food, and antacid. Ann Rheum Dis, 35: 333-338.
• Fries, J., 1996. Toward an understanding of NSAID-related adverse events: the contribution of longitudinal data. Scand J. Rheumatol Suppl., 102: 3-8.
• Fokt, H., Pereira, A., Ferreira, A. M., Cunha, A., and Aguıar, C., 2010. How do bees prevent hive infections? The antimicrobial properties of propolis. Current Research, Technology and Education Topics in Applied Microbiology and Microbial Biotechnology 1, 481-493.
• Fortson, W., Beharry, K. D. A., Nageotte, S., Sills, J. H., Stavitsky, Y., Asrat, T., et al., 2006. Vaginal versus oral indomethacin in a rabbit model for non-infection-mediated preterm birth: an afternate tocolytic approach. Am J Obstet Gynecol, 195: 1058-1064.
• Ghisalberti, E. L.,1979. Propolis: Bir inceleme. Arı Dünyası 60: 59–84.
• Glunde, K., Jie, C. F., and Bhujwalla, Z. M., 2006. Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia, 8: 758- 771.
• Halpern, S. L., 1987. Quick reference to clinical nutrition: A guide for physicians. 2nd edition ed. Philadelphia, J.B. Lippincott Company, 175-176.
• Helleberg, L., 1981. Clinical pharmacokinetics of indomethacin. Clin Pharmacokinet, 6: 245-258.
• Hida, T., Leyton, J., Makheja, A. N., Ben-Av, P., Hla, T., Martinez, A., et al., 1998. Non-small cell lung cancer cycloxygenase activity and proliferation are inhibited by non-steroidal antiinflammatory drugs. Anticancer Res., 18: 775-782.
• Hudson, N., Hawthorne, A. B., Cole, A. T., Jones, P. D. E., and Hawkey, C. J., 1992. Mechanisms of gastric and duodenal damage and protection. Hepato-Gastroenterol, 39: 31-36.
• Korkmaz, S., Koç, F., 2021. The protectıve effects of dıll (Anethum Graveolens L.) in paracetamol-induced acute toxıcatıon in mıce. International Journal of Agricultural and Natural Sciences, E-ISSN: 2651-3617 14 (1): 47-60.
• Kumova, U., ve Korkmaz, A., 2002. Önemli bir arı ürünü ‘Propolis’. Uludag Bee Journal 11-22.
• Kuropatnicki, A., Szliszka, E., and Krol, W., 2013. Historical aspect of propolis research in modern times. Evidence-Based Complementary and Alternative Medicine Volume, 11 Pages.
• Kutluca, S., Genç, F., ve Korkmaz, A., 2008. Propolis. Samsun İl Tarım Müdürlüğü Çiftçi Eğitimi ve Yayım Şubesi Yayını.
• Langman, M. J. S., 1989. Epidemiologic evidence on the association between pepticulceration and antiinflammatory drug-use. Gastroenterology, 96: 640-646.
• Lin, Y. J., Tsai, Y. J., Chen, J. S., Lin, J. S., Wu, J. M., Lin, C. H., et al., 1995. Renal effects and urinary excretion of prostaglandin following indomethacin therapy in premature infants with patent ductus arteriosus. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi,c36:104-107.
• Mannila, A., Kumpulainen, E., Lehtonen, M., Heikkinen, M., Laisalmi, M., Salo, T., et al., 2007. Plasma and cerebrospinal fluid concentrations of indomethacin in children aftercintravenous administration. J Clin Pharmacol, 47: 94-100.
• Matsuda, K., Nakamura, S., and Matsushita, T., 2006. Celecoxib inhibits nitric oxide production in chondrocytes of ligament-damaged osteoarthritic rat joints. Rheumatol International, 26: 991-995.
• McCafferty, D, M., Granger, D. N., and Wallace, J. L., 1995. Indomethacin-induced gastric injury and leukocyte adherence in arthritic versus healthy rats. Gastroenterology, 109: 1173- 1180.
• Moskvin, A. N., Alekseeva, O. S., Gutsaeva, D. R., Khmel'nitskii, A. V., and Sharapov. O. I., 2006. Effect of indomethacin on cerebral blood flow and development of oxygen convulsions. Bulletin of Experimental Biology and Medicine, 142: 26-28.
• Münstedt, K., and Zygmunt, M., 2001. Propolis-current and future medical uses. Am. Bee J. 141 (7), 507-510.
• O'Byrne, K. J., Dalgleish, A. G., Browning, M. J., Steward, W, P., and Harris, A. L., 2000. The relationship between angiogenesis and the immune response in carcinogenesis and the progression of malignant disease. Eur J Cancer, 36: 151-169.
• Paulino, N., Coutinho, L. A., Coutinho, J. R., Vilela, G. C., da Silva Leandro, V. P., and Paulino, A. S., 2015. Antiulcerogenic effect of Brazilian propolis formulation in mice. Pharmacol Pharm, 6 (12), 580.
• Popova, M., Silici, S., Kaftanoğlu, O., and Bankova, V., 2005. Antibacterial activity and qualitative and quantitative chemical composition of Turkish propolis. Bitki Tıbbı: Uluslararası Fitoterapi ve Fitofarmakoloji Dergisi 12 (3): 221-228.
• Powers, J. J., 1964. Proc. IV Int. Symp. Fd. Mikrobial. P:59-75.
• Prakash, S., Husain, M., Sureka, D. S., Shah, N. P., and Shah, N. D., 2009. Is there need to search for alternatives to indomethacin for hemicrania continua? Case reports and a review. Journal of Neurological Sciences, 277: 187-190.
• Rothermich, N. O., 1966. An Extended Study of Indomethacin: II. Clinical Therapy. JAMA, 195(13), 1102-1106.
• Sarıkahya, N. B., Gören, A. C., Okkalı, G. S., Çöven, F. O., Orman, B., Kırcı, D., Yücel, B., Kışla, D., Demirci, B., Altun, M.,
• Önem, A. N., and Nalbantsoy, A., 2021. Chemical composition and biological activities of propolis samples from different geographical regions of Turkey. Phytochemistry Letters 44, 129-136.
• Seideman, P., and von Arbin, M., 1991. Cerebral blood flow and indomethacin drug levels in subjects with and without central nervous side effects. British Journal of Clinical Pharmacology, 31: 429-432.
• Sen, T., Salam, C. A. B., Pal, S., Sen, S., and Chaudhuri, A. K. N., 2000. Effect of dothiepin on gastric ulceration mediated by lipid derived eicosanoids. Life Sci., 66: 325-330.
• Shirin, H., Moss, S. F., Kancherla, S., Kancherla, K., Holt, P. R., Weinstein, I. B., et al. 2006. Nonsteroidal anti-inflammatory drugs have bacteriostatic and bactericidal activity against Helicobacter pylori. J Gastroen Hepatol, 21: 1388-1393.
• Sigthorsson, G., Crane, R., Simon, T., Hoover, M., Quan, H., Bolognese, J., et al., 2000. COX-2 inhibition with rofecoxib does not increase intestinal permeability in healthy subjects: a double blind crossover study comparing rofecoxib with placebo and indomethacin. Gut; 47: 527-532.
• Spittle, B. J., 1982. Drug-induced psychiatric syndromes. N Z Med J., 95: 349-352.
• Subaşı, B. G., Özdal, T., and Çapanoğlu, E., 2022. Propolis and gastrointestinal tract diseases. Bee Products and Their Applications in the Food and Pharmaceutical Industries Pages 139-158.
• Suleyman, H., Akcay, F., and Altinkaynak, K., 2002b. The effect of nimesulide on the indomethacin- and ethanol-induced gastric ulcer in rats. Pharmacol Res., 45:155- 158.
• Suleyman, H., Demircan, B., and Karagoz, Y., 2007a. Anti-inflammatory and side effects of cyclooxygenase inhibitors. Pharmacol Rep; 59: 247-258.
• Suleyman, H., Halici, Z., Cadirci, E., Hacimuftuoglu, A., Keles, S., and Gocer, F., 2007b. Indirect role of alpha(2)-adrenoreceptors in anti-ulcer effect mechanism of nimesulide in rats. N-S Arch Pharmacol, 375:189-198.
• Suleyman, H., Yildirim, D., Aslan, A., Gocer, F., Gepdiremen, A., and Guvenalp, Z., 2002a. An investigation of the antiinflammatory effects of an extract from Cladonia rangiformis HOFFM. Biol Pharm Bull, 25: 10-13.
• Tharumaratnam, D., Bashford, S., and Khan, S. A., 2000. Indomethacin induced psychosis. Postgraduate Medical Journal, 76: 736-737.
• Toy, N. Ö., ve Şahinler, N., 2019. Balıkesir ili propolis örneklerinin kimyasal yapısı. 4 th International Anatolian Agriculture, Food Environment and Biology Congress Turkey, s259-269.
• Van Overmeire, B., Smets, K., Lecoutere, D., Van de Broek, H., Weyler, J., De Groote, K., et al., 2000. A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. The New England Journal of Medicine, 343: 674-681.
• Villanueva, M., González, M., Fernandez, H., Wilson, M., Manquián, N., Otth, C., and Otth, L., 2015. In vitro antibacterial activity of chilean propolis against helicobacter pylori. Rev Chilena Infectol 32 (5), 530-535.
• Villegas, I., La Casa, C., de la Lastra, C. A., Motilva, V., Herrerias, J. M., Martin, M. J., 2004. Mucosal damage induced by preferential COX-1 and COX-2 inhibitors: role of prostaglandins and inflammatory response. Life Sci., 74: 873-884.
• Wagh, V. D., 2013. Propolis: A wonder bees product and ıts pharmacological potentials. Advances in Pharmacological Sciences Volume, 11 Pages.
• Weinstein, S., A., Teixeira, E., Negri, G., and Message, D., 2005. Origin and chemical variation of Brazilian propolis. Evidence Based Complementary and Alternative Medicine 2, 33–38.
• Zehetgruber, H., Grubl, A., Goll, A., Schwameis, E., Wurnig, C., and Giurea, A., 2005. [Prevention of heterotopic ossification after THA with indomethacin: analysis of risk factors]. Z Orthop Ihre Grenzgeb 2005;143: 631-637.