Sıçanlarda İndometazin İle İndüklenen Mide Ülseri Üzerine Krom Pikolinatın Koruyucu Etkileri

Yıl 2019, Cilt: 8 Sayı: 3, 237 - 244, 30.09.2019

Gözde Atila Uslu , Hamit Uslu

Öz

Bu çalışmada, nonsteroid anti-inflamatuar
ilaçlardan biri olan indometazin ile indüklenen gastrik lezyonlar üzerine krom
pikolinatın (Crpic) koruyucu etkilerinin araştırılması amaçlandı. Araştırmada
40 adet dişi Sprague-Dawley sıçan kullanıldı. Sıçanlar eşit olarak dört gruba
ayrıldı, Kontrol (K), Krom pikolinat + İndomethazin (Crpic+İND), İndomethazin
(İND) and Pantoprazol + İndomethazin (PAN+İND). Sırasıyla I gruba sadece
Di-metil sülfoksit (DMSO) verildi, grup II'ye 300 µg/kg Crpic verildi, grup
III'e DMSO verildi ve IV grubuna 5 mg/kg pantoprazol verildi. Çalışmanın 11.
gününde, II, III ve IV gruplarına tek doz 100 mg/kg indometazin oral olarak
verildi. C-reaktif protein (CRP) düzeyleri, İND grubunda kontrol grubuna göre
daha yüksekti (I-III p<0,001, I-II, IV p<0,05). Ancak Crpic ve pantoprazol
gruplarında tek başına indometazin ile tedavi edilen gruba göre anlamlı
düşüşler gözlendi (p<0,01). Siklooksijenaz-2 (COX-2) düzeyleri indometazin
uygulaması ile artarken (p<0,001) Crpic (p<0,001) ve pantoprazol (p<0,01)
uygulamalarıyla anlamlı olarak azaldı. Tümör nekrozis faktör-alfa (TNF-α)
(p<0,05) ve interlökin-6 (IL-6) (p<0,01) seviyeleri, İND grubunda önemli
ölçüde artmıştır. Krom pikolinat ve pantoprazol gruplarında TNF-α ve IL-6
düzeylerinde bazı düşüşler vardı, ancak bu düşüşler anlamlı değildi. Sonuç
olarak; Krom pikolinatın, inflamasyonun patogenezinde önemli bir rol oynayan
COX-2 ve CRP seviyelerini önemli ölçüde azalttığı bulunmuştur. Ayrıca krom
pikolinatın indometazin ile indüklenen gastrik lezyonları önlemede oldukça
etkili olduğu belirlendi. 

Anahtar Kelimeler

Mide Ülseri, Krom pikolinat, İndomethazin, Siklooksijenaz-2

Protective Effects of Chromium Picolinate on Indomethacin-Induced Stomach Ulcer in the Rat

Öz

In the present study, it was aimed to
investigate the protective effects of chromium picolinate (Crpic) on gastric
lesions induced by indomethacine, one of the non-steroid anti-inflammatory
drugs. Forty female Sprague-Dawley rats were used in this research. The rats
were equally divided into four groups, namely Control (C), Chromium Picolinate
+ Indomethacine (Crpic+IND), Indomethacine (IND) and Pantoprazole +
Indomethacine (PAN+IND). Respectively the group I was given Dimethyl Sulfoxide
(DMSO) only, the group II was given 300 μg/kg Crpic, group III was given (DMSO)
and the group IV was given 5 mg/kg pantoprazole orally. On the 11th day of the
study, a single dose of 100 mg/kg indomethacine was administered orally to the
II, III and IV groups. C-reactive protein (CRP) levels was higher than the
control group IND group (I-III p<0.001, I-II, IV p<0.05). However,
significant decreases were observed in the Crpic and pantoprazole groups
compared to the group treated with indomethacine alone (p<0.01).
Cyclooxygenase-2 (COX-2) levels were increased by indomethacine administration
(p<0.001), whereas Crpic (p<0.001) and pantoprazole (p<0.01)
applications significantly decreased. Tumor necrosis factor-alpha (TNF-α)
(p<0.05) and interleukin-6 (IL-6) (p<0.01), levels increased significantly
in İND group. There were some decreases in TNF-α and IL-6 levels in chromium
picolinate and pantoprazole groups, but these decreases were not significant.
As a result; it has been found that chromium picolinate significantly reduces
COX-2 and CRP levels, which play an important role in the pathogenesis of
inflammation. Furthermore, it was determined that chromium picolinate was very
effective in preventing indomethacin-induced gastric lesions. 

Anahtar Kelimeler

Stomach ulcer, Chromium picolinate, Indomethacine, Cyclooxygenase-2

Kaynakça

• 1. Shrivastava, R, Upreti, RK, Seth, PK, Chaturvedi, UC. (2002). Effects of chromium on the immune system. Pathogens and Disease, 34(1),1-7.
• 2. Geyikli, İ, Bayıl, S. (2008). Kromun İnsülin Duyarlılığı İle İlişkisi. Gaziantep Tıp Dergisi, 14,59-63.
• 3. John, BV. (2000). The Biochemistry of Chromium. J Nutr, 130,715-718.
• 4. Bagchi, D, Bagchi, M, Stohs, SJ. (2001). Chromium (VI)-induced oxidative stress, apoptotic cell death and modulation of p53 tumor suppressor gene. Mol. Cell. Biochem, 222,149-58.
• 5. Anderson, RA. (1998). Recent advances in the clinical and biochemical manifestation of chromium deficiency in human and animal nutrition. J Trace Elem Exper Med, 11,2412-250.6. Anderson, RA. (2000). Chromium in the prevention and control of diabetes. Diabetes Metab, 26,22-27.
• 7. Mooradian, AD, Morley, JE. (1987). Micronutrient status in diyabetes mellitus. J Clin Nutr, 45,877.
• 8. Ganguly, R, Sahu, S, Ohanyan, V, Chilian, WM, Raman, P. (2014). Atheroprotective Mechanism of Chromium Picolinate in Streptozotocin-Induced Diabetic ApoE-/-Mice, Arteriosclerosis, Thrombosis, and Vascular Biology, 34,Abstract 645.
• 9. Sahin, K, Tuzcu, M, Orhan, C, Sahin, N, Kucuk, O, Ozercan, IH et al. (2013). Anti-diabetic activity of chromium picolinate and biotin in rats with type 2 diabetes induced by high-fat diet and streptozotocin. British Journal of Nutrition, 110(2),197-205.
• 10. Atila, G, Yüce, A. (2016). Effects of the Trigonella foenum-graecum L. seed extract and chromium picolinate supplementation in streptozotocin induced diabetes in rats. Indian Journal of Traditional Knowledge, 15(3),447-452.
• 11. Anderson, RA. (1998). Chromium, glucose intolerance and diabetes. J Am Coll Nutr, 17(6),548-555.
• 12. Jain, SK, Rains, JL, Croad, JL. (2007). Effect of chromium niacinate and chromium picolinate supplementation on lipid peroxidation, TNF-α, IL-6, CRP, glycated hemoglobin, triglycerides, and cholesterol levels in blood of streptozotocin-treated diyabetic rats. Free Radical Biology & Medicine, 43,1124–1131.
• 13. Sundaram, B, Aggarwal, A, Sandhir, R. (2013). Chromium picolinate attenuates hyperglycemia-induced oxidative stress in streptozotocin-induced diabetic rats. Journal of Trace Elements in Medicine and Biology, 27(2),117-121.
• 14. Pechova, A, Pavlata, L. (2007). Chromium as an essential nutrient: A review. Veterinarni Medicina, 52(1),1-18.
• 15. Anderson, RA, Bryden, NA, Polansky, MM, Reiser, S. (1990). Urinary chromium excretion and insulinogenie properties of carbohydrates. Am J Clin Nun, 55,864.
• 16. Borel, JS, Majerus, TC, Polansky, MM, Moser, PB, Anderson, RA. (1984). Chromium intake and urinary chromium excretion of trauma patients. Biol. Trace Element Res, 6(4),317-326.
• 17. Furst, DE, Ulrich, RW, Prakash, S. (2012). Nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, nonopioid analgesics and drugs used in gout (Chapter 36). In: Katzung BG, Masters SB, Trevor AJ, editors. Basic and clinical pharmacology. 12nd edition. United States: McGraw Hill.
• 18. Boyacioglu, M, Kum, C, Sekkin, S, Yalinkilinc, HS, Avci, H, Epikmen, ET et al. (2016). The effects of lycopene on DNA damage and oxidative stress on indomethacin-induced gastric ulcer in rats. Clinical Nutrition, 35(2),428-435.
• 19. Crofford, LJ, Lipsky, PE, Brooksi P, Abramsoni SB, Simoni LS, Van De Puttei L. (2000). Basic biology and clinical application of specific cyclooxygenase‐2 inhibitors. Arthritis & Rheumatology, 43(1),4-13.
• 20. Chatterjee, M, Saluja, R, Kanneganti, S. Chinta, S, Dikshit, M. (2007). Biochemical and molecular evaluation of neutrophil NOS in spontaneously hypertensive rats. Mol. Cell. Bio, 53, 84–93.
• 21. Choi, JI, Raghavendran, HRB, Sung, NY, Kim, JH, Chun, BS, Ahn, DH et al. (2010). Effect of fucoidan on aspirin-induced stomach ulceration in rats. Chem. Biol. Interact, 183,249–254.
• 22. Hussein, S.A, Karousa, MM, Amin, A, Awadalla, MA. (2016). Curcumin ameliorates Ethanol induced Gastric Mucosal Erosion in Rats via alleviation of Oxidative Stress and Regulation of Pro-Inflammatory Cytokines and NF-kappa B activation. Natural Science, 4(4),466-476.
• 23. Özbakiş-Dengiz, G, Hekimoğlu, A, Kandemir, N, Kurcer, Z. (2012). Effects of statins in an indomethacin-induced gastric injury model in rats. The Turkish Journal of Gastroenterology, 23(5),456-462.
• 24. Tekin, ME. (2010), Sağlık Bilimleri için Örneklerle Bilgisayarda istatistik, Selçuk Üniversitesi Basımevi, 2. Baskı, Konya, 71-88.
• 25. Mertz, W, Abernathy, CO, Olin, SS. (1994). Risk Assessment of Essential Elements, ILSI Press, Washington, DC, 19-38.
• 26. Anderson, RA, Bryden, NA, Polansky, MM. (1997). Lack of toxicity of chromium chloride and chromium picolinate. J Am Coll Nutr, 16,273-279.
• 27. Jain, SK, Kannan, K. (2001). Chromium Chloride Inhibits Oxidative Stress and TNF-a Secretion Caused by Exposure to High Glucose in Cultured U937 Monocytes. Biochemical and Biophysical Research Communications, 289,687–691.
• 28. Jain, SK, Patel, P, Rogier, K, Jain, SK. (2006). Trivalent chromium inhibits protein glycation and lipid peroxidation in high glucose treated erythrocytes. Antioxidant Redox Signaling, 8,238–241.
• 29. Shimizu, N, Watanabe, T, Arakawa, T, Fujiwara, Y, Higuchi, K, Kuroki, T. (2000). Pentoxifylline accelerates gastric ulcer healing in rats: Roles of tumor necrosis factor alpha and neutrophils during the early phase of ulcer healing. Digestion, 61(3),157–164.
• 30. Gao, Y, Zhou, S, Wen, J, Huang, M, Xu, A. (2002). Mechanism of the antiulcerogenic effect of Ganoderma lucidum polysaccharides on indomethacin-induced lesions in the rat. Life sciences, 72(6),731-745.
• 31. Wallace, JL, Mcknight, W, Miyasaka, M, Tamatani, T, Paulson, J, Anderson, DC. (1993). Role of endothelial adhesion molecules in NSAID-induced gastric mucosal injury. Am J Physiol, 265,G993–998.
• 32. Okada, A, Kinoshita, Y, Waki, S, Fukui, H, Maekawa, T, Matsushima, Y, et al. (1998). Rat gastric mucosal cells express ICAM-1 and proinflammatory cytokines during indomethacin induced mucosal injury. J Lab Clin Med, 131(6),538–547.
• 33. Kurt, H, Özbayer, C, Değirmenci, İ, Burukoğlu, D, Saadat, SM, Üstüner, MC et al. (2016). İndomethazine Bağlı Oluşan Gastrik Mukozal Hasar Üzerine Hypericum Perforatum Yağının Koruyucu Etkisi. Bozok Tıp Derg, 6(3),62-68.
• 34. Heeba, GH, Hassan, MK, Amin, RS. (2009). Gastroprotective effect of simvastatin against indomethacin-induced gastric ulcer in rats: role of nitric oxide and prostaglandins. European journal of pharmacology, 607(1),188-193.
• 35. Halter, F, Tarnawski, AS, Schmassmann, A, Peskar, BM. (2001). Cyclooxygenase 2-implications on maintenance of gastric mucosal integrity and ulcer healing: controversial issues and perspectives. Gut, 49(3),443-453.
• 36. Warner, TD, Giluliano, F, Vojnovic, I, Bukasa, A, Mitchell, JA, Vane, JR. (1999). Nonsteroid drug selectivities for cyclo-oxygenase rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. Proc Natl Acad Sci USA, 96,7563–7568.
• 37. Süleyman, H, Akçay, F, Altinkaynak, K. (2002). The effect of nimesulide on the indomethacin-and ethanol-induced gastric ulcer in rats. Pharmacological Research, 45(2),155-158.
• 38. Mitchell, JA, Warner, TD. (1999). Cyclo-oxygenase-2: pharmacology, physiology, biochemistry and relevance to NSAID therapy. Br J Pharmacol, 128,1121–1132.
• 39. Shigeta, JI, Takahashi, S, Okabe, S. (1998). Role of cyclooxygenase-2 in the healing of gastric ulcers in rats. Journal of Pharmacology and Experimental Therapeutics, 286(3),1383-1390.