Abstract
Diabetes mellitus causes structural and functional impairment of the system in the organism by affecting various organs and structures. In this study, we aimed to examine the changes in female rat heart tissue histologically by creating experimental diabetes.
16 female adult rats were used in the study. Rats were randomly divided into two groups as control and 3- month diabetes. The diabetes group was formed from subjects with blood glucose levels above 250mg/dl 72 hours after 40 mg / kg streptozotocin administration. At the end of the experiment, the heart tissues of the subjects were removed and taken into formaldehyde solution. To examine the histological structure, hematoxylin-eosin (H-E) and immunohistochemically neuronal nitric oxide syntahase (nNOS) and inducible nitric oxide syntahase (iNOS) were stained.
Heart tissue sections belonging to the control group had histologically normal appearance. In the diabetes group heart tissue sections, vacuolization in some cells and eosinophilic increase in the cytoplasm of some cells were observed. The nNOS and iNOS immunreactivity was observed to be decreased in the diabetes group compared to the control group, but the decrease was not statistically significant.
As a chronic disease, DM causes histological damage to the heart tissue. The resulting damage causes a decrease in nNOS and iNOS expression. It is important to maintain NOS enzyme levels in order to protect tissue from the harmful effects of diabetes and ensure normal physiological conditions.
Keywords
Supporting Institution
Erciyes University BAP Unit
Project Number
TDK-4258
References
- 1. Kenny HC, Abel ED. Heart Failure in Type 2 Diabetes Mellitus. Circ Res. 2019;124(1):121-41.
- 2. Lee HW, Lee SJ, Lee MY, Park MW, Kim SS, Shin N, et al. Enhanced cardiac expression of two isoforms of matrix metalloproteinase-2 in experimental diabetes mellitus. PLoS One. 2019;14(8):e0221798.
- 3. Mutavdzin S, Gopcevic K, Stankovic S, Jakovljevic Uzelac J, Labudovic Borovic M, Djuric D. The Effects of Folic Acid Administration on Cardiac Oxidative Stress and Cardiovascular Biomarkers in Diabetic Rats. Oxid Med Cell Longev. 2019;2019:1342549.
- 4. Stuehr DJ, Kwon NS, Nathan CF, Griffith OW, Feldman PL, Wiseman J. N omega-hydroxy-L-arginine is an intermediate in the biosynthesis of nitric oxide from L-arginine. J Biol Chem. 1991;266(10):6259-63.
- 5. Lowenstein CJ, Dinerman JL, Snyder SH. Nitric oxide: a physiologic messenger. Ann Intern Med. 1994;120(3):227-37.
- 6. Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991;43(2):109-42.
- 7. Alderton WK, Cooper CE, Knowles RG. Nitric oxide synthases: structure, function and inhibition. Biochem J. 2001;357(Pt 3):593-615.
- 8. Massion PB, Pelat M, Belge C, Balligand JL. Regulation of the mammalian heart function by nitric oxide. Comp Biochem Physiol A Mol Integr Physiol. 2005;142(2):144-50.
- 9. Sonmez MF, Kilic E, Karabulut D, Cilenk K, Deligonul E, Dundar M. Nitric oxide synthase in diabetic rat testicular tissue and the effects of pentoxifylline therapy. Syst Biol Reprod Med. 2016;62(1):22-30.
- 10. Abdel-Hamid AA, Firgany Ael D. Atorvastatin alleviates experimental diabetic cardiomyopathy by suppressing apoptosis and oxidative stress. J Mol Histol. 2015;46(4-5):337-45.
- 11. Li J, Peng L, Du H, Wang Y, Lu B, Xu Y, et al. The Protective Effect of Beraprost Sodium on Diabetic Cardiomyopathy through the Inhibition of the p38 MAPK Signaling Pathway in High-Fat-Induced SD Rats. Int J Endocrinol. 2014;2014:901437.
- 12. Karabulut D, Ulusoy HB, Kaymak E, Sonmez MF. Therapeutic effects of pentoxifylline on diabetic heart tissue via NOS. Anatol J Cardiol. 2016;16(5):310-5.
- 13. Nasrolahi O, Khaneshi F, Rahmani F, Razi M. Honey and metformin ameliorated diabetes-induced damages in testes of rat; correlation with hormonal changes. Iran J Reprod Med. 2013;11(12):1013-20.
- 14. Ansley DM, Wang B. Oxidative stress and myocardial injury in the diabetic heart. J Pathol. 2013;229(2):232-41.
- 15. Palmer RM, Moncada S. A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem Biophys Res Commun. 1989;158(1):348-52.
- 16. Kılınç A, Kılınç K. Nitirik oksit Biyolojik Fonksiyonları ve Toksik Etkileri. Ankara: Palme Yayıncılık. 2003:1-50.
- 17. ÇEKMEN MB, TURGUT M, TÜRKÖZ Y, AYGÜN AD, GÖZÜKARA EM. Nitrik Oksit (NO) ve Nitrik Oksit Sentaz (NOS)'ınFizyolojik ve Patolojik Özellikleri. Turkiye Klinikleri Journal of Pediatrics. 2001;10(4):226-35.
- 18. Hoang HH, Padgham SV, Meininger CJ. L-arginine, tetrahydrobiopterin, nitric oxide and diabetes. Curr Opin Clin Nutr Metab Care. 2013;16(1):76-82.
- 19. Hamilton SJ, Watts GF. Endothelial dysfunction in diabetes: pathogenesis, significance, and treatment. Rev Diabet Stud. 2013;10(2-3):133-56.
- 20. Li M, Fang H, Hu J. Apelin13 ameliorates metabolic and cardiovascular disorders in a rat model of type 2 diabetes with a highfat diet. Mol Med Rep. 2018;18(6):5784-90.
- 21. Atta MS, El-Far AH, Farrag FA, Abdel-Daim MM, Al Jaouni SK, Mousa SA. Thymoquinone Attenuates Cardiomyopathy in Streptozotocin-Treated Diabetic Rats. Oxid Med Cell Longev. 2018;2018:7845681.
- 22. Said MA. Vitamin D attenuates endothelial dysfunction in streptozotocin induced diabetic rats by reducing oxidative stress. Arch Physiol Biochem. 2020:1-5.
Abstract
Diyabetes mellitus organizmada çeşitli organ ve yapıları etkileyerek sistemin yapısal ve fonksiyonel olarak bozulmasına sebep olur. Bu çalışmada deneysel diyabet oluşturularak dişi sıçan kalp dokusundaki değişiklikleri hstolojik olarak incelemeyi amaçladık. Çalışmada 16 adet dişi erişkin sıçan kullanıldı. Sıçanlar kontrol (n=8) ve 3 aylık diyabet olmak üzere rastgele iki gruba ayrıldı. Diyabet grubu 40 mg/kg streptozotosin uygulamasından 72 saat sonra kan glukoz değerleri 250mg/dl üzerinde olan deneklerden oluşturuldu. Deney sonunda deneklerin kalp dokuları çıkarılarak formaldehid solüsyonuna alındı. Histolojik yapıyı incelemek amacıyla hematoksilen-eozin ve immunohistokimyasal olarak neuronal nitric oxide syntahase (nNOS) and inducible nitric oxide synthase (iNOS) boyandı. Kontrol grubuna ait kalp dokusu kesitleri histolojik olarak normal görünüme sahipti. Diyabet grubu kalp dokusu kesitlerinde bazı hücrelerde vakuolizasyon, bazı hücrelerin sitoplazmasında eozinofilik artış olduğu gözlendi. nNOS ve iNOS immunreaktivitesi kontrol grubuna kıyasla diyabet grubunda azaldığı gözlendi, fakat bu azalma istatistiksel olarak anlamlı değildi. DM kronik bir hastalık olarak kalp dokusunda histolojik hasara sebep olmaktadır. Ortaya çıkan hasar nNOS ve iNOS ekspresyonunun azalmasına sebep olmaktadır. Diyabetin zararlı etkilerinden dokunun korunması ve normal fizyolojik şartların sağlanması için NOS enzim seviyelerinin korunması önemlidir.
Keywords
Project Number
TDK-4258
References
- 1. Kenny HC, Abel ED. Heart Failure in Type 2 Diabetes Mellitus. Circ Res. 2019;124(1):121-41.
- 2. Lee HW, Lee SJ, Lee MY, Park MW, Kim SS, Shin N, et al. Enhanced cardiac expression of two isoforms of matrix metalloproteinase-2 in experimental diabetes mellitus. PLoS One. 2019;14(8):e0221798.
- 3. Mutavdzin S, Gopcevic K, Stankovic S, Jakovljevic Uzelac J, Labudovic Borovic M, Djuric D. The Effects of Folic Acid Administration on Cardiac Oxidative Stress and Cardiovascular Biomarkers in Diabetic Rats. Oxid Med Cell Longev. 2019;2019:1342549.
- 4. Stuehr DJ, Kwon NS, Nathan CF, Griffith OW, Feldman PL, Wiseman J. N omega-hydroxy-L-arginine is an intermediate in the biosynthesis of nitric oxide from L-arginine. J Biol Chem. 1991;266(10):6259-63.
- 5. Lowenstein CJ, Dinerman JL, Snyder SH. Nitric oxide: a physiologic messenger. Ann Intern Med. 1994;120(3):227-37.
- 6. Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991;43(2):109-42.
- 7. Alderton WK, Cooper CE, Knowles RG. Nitric oxide synthases: structure, function and inhibition. Biochem J. 2001;357(Pt 3):593-615.
- 8. Massion PB, Pelat M, Belge C, Balligand JL. Regulation of the mammalian heart function by nitric oxide. Comp Biochem Physiol A Mol Integr Physiol. 2005;142(2):144-50.
- 9. Sonmez MF, Kilic E, Karabulut D, Cilenk K, Deligonul E, Dundar M. Nitric oxide synthase in diabetic rat testicular tissue and the effects of pentoxifylline therapy. Syst Biol Reprod Med. 2016;62(1):22-30.
- 10. Abdel-Hamid AA, Firgany Ael D. Atorvastatin alleviates experimental diabetic cardiomyopathy by suppressing apoptosis and oxidative stress. J Mol Histol. 2015;46(4-5):337-45.
- 11. Li J, Peng L, Du H, Wang Y, Lu B, Xu Y, et al. The Protective Effect of Beraprost Sodium on Diabetic Cardiomyopathy through the Inhibition of the p38 MAPK Signaling Pathway in High-Fat-Induced SD Rats. Int J Endocrinol. 2014;2014:901437.
- 12. Karabulut D, Ulusoy HB, Kaymak E, Sonmez MF. Therapeutic effects of pentoxifylline on diabetic heart tissue via NOS. Anatol J Cardiol. 2016;16(5):310-5.
- 13. Nasrolahi O, Khaneshi F, Rahmani F, Razi M. Honey and metformin ameliorated diabetes-induced damages in testes of rat; correlation with hormonal changes. Iran J Reprod Med. 2013;11(12):1013-20.
- 14. Ansley DM, Wang B. Oxidative stress and myocardial injury in the diabetic heart. J Pathol. 2013;229(2):232-41.
- 15. Palmer RM, Moncada S. A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem Biophys Res Commun. 1989;158(1):348-52.
- 16. Kılınç A, Kılınç K. Nitirik oksit Biyolojik Fonksiyonları ve Toksik Etkileri. Ankara: Palme Yayıncılık. 2003:1-50.
- 17. ÇEKMEN MB, TURGUT M, TÜRKÖZ Y, AYGÜN AD, GÖZÜKARA EM. Nitrik Oksit (NO) ve Nitrik Oksit Sentaz (NOS)'ınFizyolojik ve Patolojik Özellikleri. Turkiye Klinikleri Journal of Pediatrics. 2001;10(4):226-35.
- 18. Hoang HH, Padgham SV, Meininger CJ. L-arginine, tetrahydrobiopterin, nitric oxide and diabetes. Curr Opin Clin Nutr Metab Care. 2013;16(1):76-82.
- 19. Hamilton SJ, Watts GF. Endothelial dysfunction in diabetes: pathogenesis, significance, and treatment. Rev Diabet Stud. 2013;10(2-3):133-56.
- 20. Li M, Fang H, Hu J. Apelin13 ameliorates metabolic and cardiovascular disorders in a rat model of type 2 diabetes with a highfat diet. Mol Med Rep. 2018;18(6):5784-90.
- 21. Atta MS, El-Far AH, Farrag FA, Abdel-Daim MM, Al Jaouni SK, Mousa SA. Thymoquinone Attenuates Cardiomyopathy in Streptozotocin-Treated Diabetic Rats. Oxid Med Cell Longev. 2018;2018:7845681.
- 22. Said MA. Vitamin D attenuates endothelial dysfunction in streptozotocin induced diabetic rats by reducing oxidative stress. Arch Physiol Biochem. 2020:1-5.
Details
| Primary Language | English |
|---|---|
| Subjects | Clinical Sciences |
| Journal Section | Research Articles |
| Authors | |
| Project Number | TDK-4258 |
| Publication Date | June 29, 2020 |
| Published in Issue | Year 2020 Volume: 1 Issue: 1 |
