İndometazin ile Gastrik Hasar Oluşturulmuş Sıçanların Mide Dokusunda AOPP Ve Total Sülfidril Düzeyi Üzerine Tarantula Cubensis Alkolik Ekstraktı’nın Etkisi

Yıl 2025, Cilt: 1 Sayı: 3, 88 - 95, 29.11.2025

Ufuk Mercan Yücel

https://doi.org/10.65308/gjohbs.2025.013

Öz

Tarantula cubensis örümceğinin alkolik ekstraktı (TCAE) veteriner sahada homeopatik ilaç olarak kullanılmaktadır. TCAE antiinflamatuar, antitümör, nekrotizan etki ve yara iyileşmesi gibi birçok terapötik etkiye sahiptir. Hücrenin oksidatif stres durumunu değerlendirmek için kullanılan birçok belirteç vardır. Oksijen radikallerinin hücredeki proteinlerle reaksiyonu ile oluşan ilerlemiş protein oksidasyon ürünleri ‘advanced oxidative protein products’ (AOPP) bu belirteçlerden biridir. Total sülfidril (TSG) ise antioksidan durumun göstergesi olarak kabul edilmektedir. Bu çalışmada indometazin ile gastrik hasar oluşturulmuş sıçanların mide dokusunda AOPP ve TSG düzeyi üzerine TCAE’nin etkisinin incelenmesi amaçlandı. Bu amaçla sıçanlar kontrol grubu, ülser grubu (25mg/kg indometazin), İndometazin + Lansoprazol (25mg/kg indometazin + 30 mg/kg lansoprazol) alan ülser grubu (referans anti-ülser ilaç), İndometazin + TCAE (25mg/kg indometazin + 200 µg/kg Theranekron) alan ülser grubu olmak üzere 4 gruba ayrıldı (n=7). Lansoprazol ve TCAE belirtilen dozlarda verildikten 5 dakika sonra negatif kontrol grubu hariç tüm sıçanlara aynı şekilde oral yolla tek doz indometazin verildi ve indometazin uygulamasından altı saat sonra anestezi altında mide dokusu biyokimyasal analiz için çıkarıldı. Mide dokusunda AOPP ve TSG düzeylerinin ölçümünde spektrofotometrik yöntem kullanıldı. Çalışmada, TCAE’nin etkileri ülser tedavisinde kullanılan lansoprazolun etkileri ile karşılaştırıldı. İndometazin grubunda AOPP ve TSG düzeyinde Kontrol grubuna göre istatistiksel olarak anlamlı (p<0.05) bir artış bulundu. TCAE uygulanan grupta AOPP ve TSG düzeyleri İndometazin ve İndometazin + Lansoprazol gruplarına göre daha düşük tespit edildi. Bu çalışmada TCAE uygulaması ile AOPP düzeyinde değişikliğin olmaması ve bunun sonucunda TSG düzeyinde herhangi bir artışın belirlenmemesi nedeniyle indometazin uygulaması sonucu oluşan gastrik hasara karşı TCAE’nin koruyucu bir rolünün olabileceği tespit edildi.

Etik Beyan

Bu çalışma, Van Yüzüncü Yıl Üniversitesi Hayvan Deneyleri Yerel Etik Kurulu'nun 02.05.2019 tarih ve 2019/04 sayılı kararıyla kabul edilmiştir.

Destekleyen Kurum

Bu çalışma için herhangi bir finansal destek alınmamıştır.

Teşekkür

Biyokimyasal analizler sırasındaki destekleri için Sayın Doç. Dr. Ahmet Ufuk KÖMÜROĞLU'na ve istatistiksel analizlerdeki yardımları için Prof. Dr. Sıddık KESKİN'e teşekkür ederim.

The Effect of Tarantula Cubensıs Alcoholic Extract on AOPP and Total Sulfhidryl Level in The Stomach Tissue of Gastric Damaged Rats with Indometazine

Öz

Alcoholic extract of the spider Tarantula Cubensis (TCAE) is used as a homeopathic agent in the Veterinary medicine. TCAE has many therapeutic effects such as anti-inflammatory, antitumor, necrotizing action and wound healing. There are many markers used to assess the oxidative stress state of the cell. Advanced oxidative protein products (AOPP), which are formed by the reaction of oxygen radicals with proteins in the cell, are one of these markers. Total sulfhydryl (TSG) is accepted as an indicator of antioxidant status. In this study, it was aimed to investigate the effect of TCAE on AOPP and TSG levels in the stomach tissue of rats with indomethacin-induced gastric damage. For this purpose, the rats were divided into 4 groups, including control group, ulcer group (25mg/kg indomethacin), Indomethacin + Lansoprazole (25mg/kg indomethacin + 30 mg/kg lansoprazole) ulcer group (reference anti-ulcer drug), Indomethacin + TCAE (25mg/kg indomethacin + 200 µg/kg Theranekron) ulcer group (n=7). 5 minutes after lansoprazole and TCAE were given at the indicated doses, all rats except the negative control group were given a single dose of indomethacin (25 mg/kg dose) orally in the same way, and six hours after indomethacin administration, the gastric tissue was removed for biochemical analysis under anesthesia. Spectrophotometric method was used to measure AOPP and TSG levels in gastric tissue. In the study, the effects of TCAE were compared with the effects of lansoprazole used in the treatment of ulcers. A statistically significant (p<0.05) increase was found in the AOPP and TSG levels in the indomethacin group compared to the control group. AOPP and TSG levels were found to be lower in the Indomethacin + TCAE group compared to the Indomethacin and Indomethacin + Lansoprazole groups. In this study, it was determined that TCAE may have a protective role against gastric damage caused by indomethacin administration, since there was no change in AOPP level with TCAE application and no increase in TSG level was detected as a result.

Anahtar Kelimeler

Tarantula Cubensis Alcholic Extract , Total Sulphidril , İndomethacin , Advanced oxidation protein products , Gastric damage

Etik Beyan

This study was approved by the Van Yüzüncü Yıl University Animal Experiments Local Ethics Committee with decision number 2019/04, dated 02.05.2019.

Destekleyen Kurum

This study received no financial support.

Teşekkür

I would like to thank Assoc. Prof. Dr. Ahmet Ufuk KÖMÜROĞLU for his support during the biochemical analyses and Prof. Dr. Sıddık KESKİN for his assistance with the statistical analyses.

Kaynakça

• 1. Lichtenberger LM. The hydrophobic barrier properties of gastrointestinal mucus. Annu Rev Physiol. 1995;57:565-583.
• 2. Takeuchi K. Prostaglandin EP receptors and their roles in mucosal protection and ulcer healing in the gastrointestinal tract. Adv Clin Chem. 2010;51:121-144.
• 3. Ganguly K, Kundu P, Banerjee A, Reiter RJ, Swarnakar S. Hydrogen peroxide-mediated downregulation of matrix metalloprotease-2 in indomethacin-induced acute gastric ulceration is blocked by melatonin and other antioxidants. Free Radic Biol Med. 2006;41(6):911-925.
• 4. Park SH, Hong H, Han YM, Kangwan N, Kim SJ, Kim EH, Hahm KB. Nonsteroidal anti-inflammatory drugs (NSAID) sparing effects of glucosamine hydrochloride through N-glycosylation inhibition; strategy to rescue stomach from NSAID damage. J Physiol Pharmacol. 2013;64(2):157-165.
• 5. Coşkun D. Veterinary Supportive Therapy: Tarantula Cubensis Alcoholic Extract, Inactived Parapoxvirus Ovis and Corynebacterium Cutis Lysate. Dicle Uni J Fac Vet Med. 2017;10(1):30-37.
• 6. Çakatay U, Kayalı R. The clinical importance of protein oxidation. Cerrahpaşa J Med 2004; 35: 140-149. 7. Witko-Sarsat V, Friedlander M, Nguyen Khoa T, Capeillère-Blandin C, Nguyen AT, Canteloup S, Dayer JM, Jungers P, Drüeke T, Descamps-Latscha B. Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure. J Immunol. 1998;161(5):2524-2532.
• 8. Yılmaz A, Eskiocak S, Altaner S, Turan N. The Effect of N-acetylcysteine on Protein Oxidation of Acetic Acid-Induced Colitis in Rats. J Turkish Clin Biochem. 2010;8(1): 23-33.
• 9. Kalousová M, Skrha J, Zima T. Advanced glycation end-products and advanced oxidation protein products in patients with diabetes mellitus. Physiol Res. 2002;51(6):597-604.
• 10. Shi XY, Hou FF, Niu HX, Wang GB, Xie D, Guo ZJ, Zhou ZM, Yang F, Tian JW, Zhang X. Advanced oxidation protein products promote inflammation in diabetic kidney through activation of renal nicotinamide adenine dinucleotide phosphate oxidase. Endocrinology. 2008;149(4):1829-1839.
• 11. Kaneda H, Taguchi J, Ogasawara K, Aizawa T, Ohno M. Increased level of advanced oxidation protein products in patients with coronary artery disease. Atherosclerosis. 2002;162(1):221-225.
• 12. Atabek ME, Keskin M, Yazici C, Kendirci M, Hatipoglu N, Koklu E, Kurtoglu S. Protein oxidation in obesity and insulin resistance. Eur J Pediatr. 2006;165(11):753-756.
• 13. Feeney L, Berman ER. Oxygen toxicity: membrane damage by free radicals. Invest Ophthalmol. 1976;15(10):789-792.
• 14. Ames BN. Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases. Science. 1983;221(4617):1256-1264.
• 15. Berlett BS, Stadtman ER. Protein oxidation in aging, disease, and oxidative stress. J Biol Chem. 1997;272(33):20313-20316.
• 16. Dean RT, Fu S, Stocker R, Davies MJ. Biochemistry and pathology of radical-mediated protein oxidation. Biochem J. 1997;324 (Pt 1)(Pt 1):1-18.
• 17. Esterbauer H, Zollner H. Methods for determination of aldehydic lipid peroxidation products. Free Radic Biol Med. 1989;7(2):197-203.
• 18. Takenaka Y, Miki M, Yasuda H, Mino M. The effect of alpha-tocopherol as an antioxidant on the oxidation of membrane protein thiols induced by free radicals generated in different sites. Arch Biochem Biophys. 1991;285(2):344-350.
• 19. Hu ML. Measurement of protein thiol groups and glutathione in plasma. Methods Enzymol. 1994;233:380-385.
• 20. Kanbağlı Ö. Total Thiol Levels and glutathione peroxidase activity as parameters of oxidative stres. J Istanbul Fac Med. 2011;63(3).
• 21. Guidobono F, Pagani F, Ticozzi C, Sibilia V, Pecile A, Netti C. Protection by amylin of gastric erosions induced by indomethacin or ethanol in rats. Br J Pharmacol. 1997;120(4):581-586.
• 22. Bardhan KD, Ahlberg J, Hislop WS, et al. Rapid healing of gastric ulcers with lansoprazole. Aliment Pharmacol Ther. 1994;8(2):215-220.
• 23. Ohashi T, Sakata J, Haraguchi Y, Eto T. Effect of lansoprazole on peptic ulcers. J Clin Gastroenterol. 1995;20 Suppl 2:S83-S85.
• 24. Périco LL, Rodrigues VP, Ohara R, et al. Sex-specific effects of Eugenia punicifolia extract on gastric ulcer healing in rats. World J Gastroenterol. 2018;24(38):4369-4383.
• 25. Karabacak M, Eraslan G, Kanbur M, Sarıca ZS. Effects of Tarantula cubensis D6 on aflatoxin-induced injury in biochemical parameters in rats. Homeopathy. 2015;104(3):205-210.
• 26. Kapui Z, Boér K, Rózsa I, Blaskó G, Hermecz I. Investigations of indomethacin-induced gastric ulcer in rats. Arzneimittelforschung. 1993;43(7):767-771.
• 27. Borra SK, Lagisetty RK, Mallela GR. Anti-ulcer effect of Aloe vera in non-steroidal anti-inflammatory drug induced peptic ulcers in rats. Afr J Pharmacy Pharmacol. 2011;5:1867-1871.
• 28. Minaiyan M, Sajjadi SE, Amini K. Antiulcer effects of Zataria multiflora Boiss. on indomethacin-induced gastric ulcer in rats. Avicenna J Phytomed. 2018;8(5):408-415.
• 29. Witko-Sarsat V, Friedlander M, Capeillère-Blandin C, Nguyen-Khoa T, Nguyen AT, Zingraff J, Jungers P, Descamps-Latscha B. Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int. 1996;49(5):1304-1313.
• 30. Conrad CC, Marshall PL, Talent JM, Malakowsky CA, Choi J, Gracy RW. Oxidized proteins in Alzheimer's plasma. Biochem Biophys Res Commun. 2000;275(2):678-681.
• 31. Lim PS, Cheng YM, Wei YH. Increase in oxidative damage to lipids and proteins in skeletal muscle of uremic patients. Free Radic Res. 2002;36(3):295-301.
• 32. Kılıç K, Yıldırım Z. Effects of taurine and age on liver antioxidant status and protein oxidation. Turkish J Biochem. 2008;33(4):169-174.
• 33. Cakatay U. Protein oxidation parameters in type 2 diabetic patients with good and poor glycaemic control. Diabetes Metab. 2005;31(6):551-557.
• 34. Fraschini F, Demartini G, Esposti D. Pharmacology of Silymarin. Clin. Drug Investig. 2002;22:51–65.
• 35. Cankara FN, Özmen Ö, Savaş HB, Şahin Y, Günaydın C. Gastroprotective effect of tarantula cubensis extract in the indomethacin-induced peptic ulcer model in rats. Acta Med Alanya. 2020;4(3):278-284.
• 36. Eren C, Akşit D. The Investigation Protective Effect of Tarantula Cubensis Extract in Rats Induced Experimental Gentamicin Nephrotoxicity. Animal Health Prod and Hyg. (2023) 12 (1): 31–39. 37. Şebin SÖ, Nacar T, Tanyeli A, Eraslan E, Güler MC, Toktay E, Polat E, Gedik HT. The effects of tarantula cubensis extract on renal ischemia reperfusion injury in rats. Turk J Med Sci. 2023 Apr;53(2):463-474. 38. Klisic A, Kavaric N, Vujcic S, Spasojevic-Kalimanovska V, Kotur-Stevuljevic J, Ninic A. Factorial Analysis of the Cardiometabolic Risk Influence on Redox Status Components in Adult Population. Oxid Med Cell Longev. 2021;2021:6661940.