Tarçının Deneysel Olarak İndüklenen Diyabetli Sıçanların Akciğer Dokusunda VEGF ve NF-κB İmmünoreaksiyonu Üzerindeki Etkileri

Abstract

Amaç: Diabetes mellitus, insülin eksikliği veya direncinin neden olduğu hiperglisemi olarak tanımlanan metabolik bir hastalıktır. Çalışmalarda artan kanıtlar, akciğerin diyabetik komplikasyonların hedefi olduğunu göstermiştir. Geleneksel tıp teorilerine göre tarçın, şeker hastaları için destekleyici bir tedavi yöntemi olarak kabul edilmektedir. Bu çalışmanın amacı, tarçının streptozotosin ile indüklenen deneysel diyabetik sıçanların akciğer dokusunda VEGF ve NF-κB'nin immünohistokimyasal ekspresyonu üzerindeki etkisini araştırmaktır. Gereç ve Yöntem: Otuz iki erkek sıçan rastgele dört gruba ayrıldı: Diyabet, Diyabet + tarçın, Tarçın ve Kontrol. VEGF ve NF-κB'nin akciğer dokusunda immünohistokimyasal ekspresyonu, streptavidin-biotin kompleksi kullanılarak belirlendi. Bulgular: Tarçın uygulamasının tek başına akciğer dokusunda VEGF ekspresyonunu değiştirmezken, diyabet grubunda tarçın uygulaması ile azalmış VEGF ekspresyonunun arttığı belirlendi. Gruplardaki immün boyama incelendiğinde, kontrol ve tarçın grupları arasında NF-κB immünreaksiyonu açısından bir fark gözlenmedi. Dikkat çekici bir bulgu olarak, diyabetik grubun akciğer dokusunda güçlü pozitif NF-κB reaksiyonları vardı. Ayrıca diyabet+cinnamom grubunda zayıf pozitif NF-κB reaksiyonu tespit edildi. Sonuç: Sonuç olarak bizim çalışmamızda tarçın diyabetin neden olduğu NF-κB ekspresyonundaki artışın azalmasına, azalmış VEGF ekspresyonunun ise artmasına neden olmuştur. Sonuç olarak, bu çalışmanın diyabete bağlı olarak akciğer dokusunda meydana gelebilecek olası sitokin mekanizması değişikliklerinin anlaşılmasında ve tedavi yöntemlerinin geliştirilmesinde faydalı olacağı kanaatindeyiz.

Keywords

• Akciğer
• Diyabet
• NF-KB
• VEGF
• Tarçın

Effects of Cinnamon on VEGF and NF-κB Immunoreaction in The Lung Tissue of Rats with Experimentally Induced Diabetes

Abstract

Objective: Diabetes mellitus is a metabolic disorder described as hyperglycemia induced by insulin deficiency or resistance. Increasing evidence in studies has shown that the lung is the target of diabetic complications. According to traditional medicine theories, cinnamon is considered a supportive treatment method for diabetics. The aim of this study is to investigate the effect of cinnamon on the immunohistochemical expression of VEGF and NF-κB in lung tissue of streptozotocin-induced experimental diabetic rats. Material and Method: Thirty-two male rats were randomly divided into four groups: Diabetes, Diabetes + cinnamon, Cinnamon, and Control. The immunohistochemical expression of VEGF and NF-κB in the lung tissue was determined by using the streptavidin-biotin complex method. Results: It was determined that while cinnamon application alone did not change VEGF expression in lung tissue, the decreased VEGF expression in the diabetes group increased with the cinnamon application. When the immunostaining in the groups was examined no difference was observed in NF-κB immunoreaction between the control and cinnamon groups. As a remarkable finding, in the diabetic group's lung tissue, there were strong positive NF-κB reactions. In addition, a weak positive NF-κB reaction was detected in the diabetes+cinnamom group. Conclusion: As a result, in our study cinnamon caused decreased the increase in NF-κB expression caused by diabetes and increased the decreased VEGF expression. In conclusion, we believe that this study will be useful in understanding possible cytokine mechanism changes that may occur in the lung tissue due to diabetes and in the development of treatment methods.

Keywords

• Cinnamon
• Diabetes
• Lung
• NF-KB

References

1. Daryabor G, Kabelitz D, Kalantar K. An update on immune dysregulation in obesity-related insulin resistance. Scand J Immunol. 2019;89:12747. doi: 10.1111/sji.12747.
2. Wu J, Jin Z, Yan L-J. Redox imbalance and mitochondrial abnormalities in the diabetic lung. Redox Biol. 2017;11:51-59. doi: 10.1016/j.redox.2016.11.003.
3. Zheng H, Wu J, Jin Z, Yan L-J. Potential biochemical mechanisms of lung injury in diabetes. Aging Dis. 2017;8(1):7-16. doi: 10.14336/AD.2016.0627.
4. Kuzmicki M, Telejko B, Lipinska D, Pliszka J, Szamatowicz M, Wilk J, et al. Serum irisin concentration in women with gestational diabetes. Gynecol Endocrinol. 2014;30(9):636-639. doi: 10.3109/09513590.2014.920006.
5. Zare R, Nadjarzadeh A, Zarshenas MM, Shams M, Mojtaba Heydari M. Efficacy of cinnamon in patients with type II diabetes mellitus: A randomized controlled clinical trial. Clin Nutr. 2019;38(2):549-556.doi: 10.1016/j.clnu.2018.03.003.
6. Udayaprakash NK, Ranjithkumar M, Deepa S, Sripriya N, Al-Arfaj AA, Bhuvaneswari S. Antioxidant, free radical scavenging and GC–MS composition of Cinnamomum iners Reinw. ex Blume. Ind Crops Prod. 2015;69:175-179. doi.org/10.1016/j.indcrop.2015.02.018.
7. Jitomir J, Willoughby DS. Cassia cinnamon for the attenuation of glucose intolerance and insulin resistance resulting from sleep loss. J Med Food. 2009;12(3):467-472. doi: 10.1089/jmf.2008.0128.
8. Shishodia S, Aggarwal BB. Nuclear factor-kappaB activation: a question of life or death. J Biochem Mol Biol. 2002;35(1):28-40. doi.org/10.5483/bmbrep.2002.35.1.028.

9. Davari M, Hashemi R, Mirmiran P, Hedayati M, Sahranavard S, Bahreini S, et al. Effects of cinnamon supplementation on expression of systemic inflammation factors, NF-kB and Sirtuin-1 (SIRT1) in type 2 diabetes: a randomized, double blind, and controlled clinical trial. Nutr J. 2020;19(1):1-8.
10. Zhang L, Jiang L-L, Cao Z-W. Interleukin-33 promotes the inflammatory reaction in chronic rhinosinusitis with nasal polyps by NF-κB signaling pathway. Eur Rev Med Pharmacol Sci. 2017;21(20):4501-4508.
11. Shay T, Lederer JA, Benoist C. Genomic responses to inflammation in mouse models mimic humans: we concur, apples to oranges comparisons won’t do. Proc Natl Acad Sci USA. 2015;112(4):e346. doi: 10.1073/pnas.1416629111.
12. Xie K, Wei D, Shi Q, Huang S. Constitutive and inducible expression and regulation of vascular endothelial growth factor. Cytokine Growth Factor Rev. 2004;15(5):297-324. doi: 10.1016/j.cytogfr.2004.04.003.
13. Papaioannou AI, Kostikas K, Kollia P, Gourgoulianis KI. Clinical implications for vascular endothelial growth factor in the lung: friend or foe?. Respir Res. 2006;7(1):128. doi: 10.1186/1465-9921-7-128.
14. Barratt S, Medford AR, Millar AB. Vascular endothelial growth factor in acute lung injury and acute respiratory distress syndrome. Respiration. 2014;87:329-342. doi: 10.1159/000356034.
15. Mura M, Han B, Andrade CF, Seth R, Hwang D, Waddell TK, et al. The early responses of VEGF and its receptors during acute lung injury: implication of VEGF in alveolar epithelial cell survival. Crit Care. 2006;10(5):R130. doi: 10.1186/cc5042.
16. Çetin A, Vardı N, Orman D. Deneysel diyabetin sıçan kalp dokusunda meydana getirdiği histolojik değişiklikler üzerine aminoguanidinin iyileştirici etkileri. İnönü Üniversitesi Sağlık Hizmetleri Meslek Yüksekokulu Dergisi. 2013;1(1), 17-26.
17. Hemayatkhah JV, Baqerzadeh P. The effect of cinnamon extract on ovary in adult rats treated lead acetate. Journal of Anımal Biology. 2017;9(2):1-9.
18. True LD. Principles of immunohistochemistry. New York: Gower Medical Publishing; 1990.
19. Ertuğrul T, Ceylan A. The expression profiles of NFκB, Hsp70, and TNF-α in swine urinary bladder: an immunohistochemical study. Eurasian J Vet Sci. 2022; 38(1):1-6.
20. Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev. 2002; 23(5):599-622. doi: 10.1210/er.2001-0039.
21. Zhang B, Wang D, Ji T-F, Shi L, Yu J-L.Overexpression of lncRNA ANRIL up-regulates VEGF expression and promotes angiogenesis of diabetes mellitus combined with cerebral infarction by activating NF-κB signaling pathway in a rat model. Oncotarget. 2017;8(10):17347-17359. doi: 10.18632/oncotarget.14468.
22. Sahin K, Pala R, Tuzcu M, Ozdemir O, Orhan C, Sahin N, et al. Curcumin prevents muscle damage by regulating NF-κB and Nrf2 pathways and improves performance: an in vivo model. J Inflamm Res. 2016;29(9)147-154. doi: 10.2147/JIR.S110873.
23. Warren HS, Tompkins RG, Moldawer LL, Seok J, Xu W, Mindrinos MN, et al. Mice are not men. Proc Natl Acad Sci USA. 2015;112(4):e345.
24. Taniguchi K, Karin M. NF-κB, inflammation, immunity and cancer: Coming of age. Nat Rev Immunol. 2018;18(5):309-324. doi: 10.1038/nri.2017.142.
25. Quehenberger P, Bierhaus A, Fasching P, Muellner C, Klevesath M, Hong M, et al. Endothelin 1 transcription iscontrolled by nuclear factor-kappaB in AGE-stimulated culturedendothelial cells. Diabetes. 2000;49(9):1561-1570. doi: 10.2337/diabetes.49.9.1561.
26. Zhong L, Luo Y, Huang C, Liu L. Effect of NF-κB decoy on insulin resistance of adipocytes from patients with type 2 diabetes mellitus. Diabetes Metab. 2011;37(6):520-526. doi: 10.1016/j.diabet.2011.04.004.
27. Pala HG, Erbaş O, Oltulu F, Pala EE, Aktuğ H, Yavaşoğlu A. Diyabetik sıçan overlerindeki glikoz hasarı ve NF-kappa B yolunun etkisi. Ege Journal of Medicine. 2013;52(1):32-36.
28. Coşkun ZM, Beydogan AB, Bolkent S. The effect of ghrelin treatment on cell survival and ınflammation in type 2 diabetic rat liver. Okmeydanı Tıp Dergisi. 2017;33(4):253-260. doi:10.5222/otd.2017.1099.
29. Wang G, Hu Y-X, He M-Y, Xie Y-H, Su W, Long D. Gut-lung dysbiosis accompanied by diabetes mellitus leads to pulmonary fibrotic change through the NF-κB signaling pathway. Am J Pathol. 2021;191(5):838-856. doi: 10.1016/j.ajpath.2021.02.019.
30. Ranasinghe P, Perera S, Gunatilake M, Abeywardene E, Gunapala N, Premakumara S, et al. Effects of Cinnamomum zeylanicum (Ceylon cinnamon) on blood glucose and lipids in a diabetic and healthy rat model. Pharmacognosy Res. 2012;4(2):73-9. doi: 10.4103/0974-8490.94719.
31. Mura M, dos Santos CC, Stewart D, Liu M. Vascular endothelial growth factor and related molecules in acute lung injury. J Appl Physiol. 2004;97(5):1605-1617. doi: 10.1152/japplphysiol.00202.2004.
32. Jakkula M, Le Cras TD, Gebb S, Hirth KP, Tuder RM, Voelkel NF, et al. Inhibition of angiogenesis decreases alveolarization in the developing rat lung. Am J Physiol Lung Cell Mol Physiol. 2000;279(3):600-607. doi.org/10.1152/ajplung.2000.279.3.L600.
33. Compernolle V, Brusselmans K, Acker T, Hoet P, Tjwa M, Beck H, et al. Loss of HIF-2alpha and inhibition of VEGF impair fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice. Nat Med. 2002;8(7):702-710. doi.org/10.1038/nm721.
34. Rivard A, Silver M, Chen D, Kearney M, Magner M, Annex B. Rescue of diabetes-related impairment of angiogenesis by intramuscular gene therapy with adeno-VEGF. Am J Pathol. 1999;154(2):355-63. doi: 10.1016/S0002-9440(10)65282-0.
35. İrtegün S, Deveci E. Diyabetik sıçanların testis dokusunda VEGF ve Bcl-2 ekspresyon düzeylerinin immünohistokimya ve western blot yöntemleri ile incelenmesi. Dicle Tıp Dergisi. 2016;43(4):527-533. doi: 10.5798/diclemedj.0921.2016.04.0724.
36. Şahin İnan ZD, Ünver Saraydin S: Evaluation of VEGF, cytokeratin-19 and caspase 3 immunolocalization in the lung tissue of rat with experimentally induced diabetes. Kafkas Univ Vet Fak Derg. 2019;25(3):415-420. doi: 10.9775/kvfd.2018.21141.
37. Waltenberger J, Lange J, Kranz A. Vascular endothelial growth factor- A-induced chemotaxis of monocytes is attenuated in patients with diabetes mellitus: a potential predictor for the individual capacity to develop collaterals. Circulation. 2000;102(2):185-90. doi: 10.1161/01.cir.102.2.185.
38. Han B, Baliga R, Huang H, Giannone JP, Bauer JA. Decreased cardiac expression of vascular endothelial growth factor and redox imbalance in murine diabetic cardiomyopathy. Am J Physiol Heart Circ Physiol. 2009;297(2):H829-35. doi: 10.1152/ajpheart.00222.2009.
39. Yoon YS, Uchida S, Masuo O, Cejna M, Park JS, Gwon HC, et al. Progressive attenuation of myocardial vascular endothelial growth factor expression is a seminal event in diabetic cardiomyopathy: restoration of microvascular homeostasis and recovery of cardiac function in diabetic cardiomyopathy after replenishment of local vascular endothelial growth factor. Circulation. 2005;111(16):2073-85. doi: 10.1161/01.CIR.0000162472.52990.36.
40. Subash-Babu P, Alshatwi AA, Ignacimuthu S. Beneficial anti-oxidative and antiperoxidative effect of cinnamaldehyde protect streptozotocin-induced pancreatic β-cells damage in wistar rats. Biomol Ther. 2014;22(1):47-54. doi: 10.4062/biomolther.2013.100.