The possible protective effect of melatonin on streptozotocin induced experimental diabetes

Abstract

Objective: This experimental study aims to investigate the protective effect of melatonin on the enzymes\', which regulate glucose metabolism in liver tissue. Methods: In this experimental study, four-month-old male Wistar albino rats were used. The rats were divided into 4 groups as 7 rats in each group. Rats were grouped as control group, diabetic group, melatonin protecting group, as well as melatonin treatment group. Before the streptozotocin implementation to melatonin protecting group (seven days ago) everyday at 18.00 melatonin was implemented for seven days. On the other hand melatonin was implemented to melatonin treatment group after streptozotocin implementation everyday at 18.00 for seven days. Only a single dose of streptozotocin was implemented to diabetic group. Control group had no intervention throughout the study. In the end of the experiment, blood was taken and rats were sacrificed. Before the sacrifice process rats\' fasting blood pressure was measured. Hexokinases, pyruvate kinase, glucose-6-phosphatase, fructose - 1,6-bisphosphatase, glucose -6 phosphate dehydrogenase levels were measured in the liver samples. Results: Between control and experimental groups of rats, there are statistically significant differences between control and experimental groups for all parameters. Melatonin protecting group levels of investigated parameters were more close to that of control groups\' values and results are statistically significant. Moreover, melatonin treatment group showed a protective effect. However it is not effective as melatonin protecting group. Conclusion: It can be suggested that melatonin shows protective effect on enzymes related to glucose metabolism in the liver tissue in a model of streptozotocin-induced experimental diabetes. J Clin Exp Invest 2014; 5 (4): 592-598

Keywords

• Melatonin, liver, diabetes, streptozotocin.

Streptozotosin ile oluşturulan deneysel diyabette melatonin\'in olası koruyucu etkisinin araştırılması

Öz

Amaç: Bu deneysel çalışmada streptozotosin ile oluşturulmuş deneysel diyabette, melatoninin karaciğer dokusunda glikoz metabolizmasını düzenleyen enzimler üzerindeki koruyucu etkisini araştırmayı amaçladık. Yöntemler: Bu deneysel çalışmada dört aylık erkek Wistar albino sıçanlar kullanıldı. Çalışmamız için her grupta yedi hayvan olmak üzere dört grup oluşturuldu. Sıçanlar; kontrol grubu, diyabet grubu, melatonin koruyucu grup, melatonin tedavi grubu şeklinde gruplandırıldı. Melatonin koruyucu gruba streptozotosin uygulanmasından yedi gün öncesinden başlanılarak her gün saat 18.00\'da, melatonin tedavi grubuna ise streptozotosin uygulandıktan sonra yedi gün süresince her gün saat 18.00\'da melatonin uygulandı. Diyabet grubuna sadece streptozotosin tek doz uygulandı. Kontrol grubuna herhangi bir işlem yapılmadı. Çalışma sonunda sıçanların kalbinden kan alınarak sakrifiye edildi. Sakrifiye işlemi öncesinde açlık kan şekerleri ölçüldü. Alınan karaciğer örneklerinde Hekzokinaz, Pirüvat Kinaz, Glikoz - 6- Fosfataz, Fruktoz - 1,6- Bifosfataz, Glikoz -6- Fosfat Dehidrogenaz düzeyleri ölçüldü. Bulgular: Sıçanların kontrol ve deney grupları arasında tüm parametreler açısından istatistiksel olarak anlamlı fark saptandı. Melatonin koruyucu grup, araştırılan parametrelerimizin kontrol grubu değerlerine döndürmeye yardımcı olmuş ve sonuçlar istatistiksel olarak anlamlı bulunmuştur. Melatonin tedavi grubu da etkisini olumlu yönde göstermiş fakat istatistiksel olarak anlamlı sonuç vermemiştir. Sonuç: Streptozotosin ile oluşturulan deneysel diyabette, karaciğer dokusunda glikoz metabolizması ile ilgili enzimler üzerinde melatoninin koruyucu etki gösterdiği söylenebilir.

Anahtar Kelimeler

• Melatonin, karaciğer, diyabet, streptozotosin

References

1. 1. Deshpande A. D, Harris-Hayes M, and Schootman M. Epidemiology of diabetes and diabetes-related complications. Phys Ther 2008; 88:1254-1264.
2. 2. Szkudelski T. The mechanism of alloxan and streptozotocin action in b cells of the rat pancreas. Physiol Res 2001;50:536-546.
3. 3. Lerner AB, Case JD, Takahashi Y, et al. Isolation of melatonin, the pineal gland factor that lightens melanocytes. J Am Chem Soc 1958;80:2587-2592.
4. 4. Reiter RJ, Tan DX, Kim SJ, Wenbo QI. Melatonin as a pharmacological agent against oxidative damage to lipids and DNA. Proc West Pharm Soc 1998;41:229- 236.
5. 5. Ferbeyre G, Lowe SW, The price of tumour suppression, Nature 2002;415:26-27.
6. 6. Shima T, Chun SJ, Niijima A, et al. Melatonin suppress hyperglisemia caused by intracerebroventricular injection of 2-Deoxy- D-Glucose in rats. Neuroscience Letters 1997;226:119-122.
7. 7. Yavuz O, Cam M, Bukan N, et al. Protective effect of melatonin on β-cell damage in streptozotocin-induced diabetes in rats. Acta Histochem 2003;105 :261-266.
8. 8. M. E. Montano, Molpeceres V, Mauriz J.L. Effect of melatonin supplementation on food and water intake in streptozotocin-diabetic and non-diabetic male wistar rats. Nutr Hosp 2010;25:247-254.

9. 9. Levinthal GN, Tavill AS. Liver Disease and Diabetes Mellitus. Clin Diabet 1999;17:245-250.
10. 10. Keembiyehetty C, Augustin R, Carayannopoulos M. O, et al. Mouse glucose transporter 9 splice variants are expressed in adult liver and kidney and are up-regulated in diabetes. Mol Endocrinol, 2006;20:686-697.
11. 11. Arendt J. Melatonin. Clin Endocrinol 1988;29:205- 229. 12. Vardı N, Iraz M, Öztürk F, ve ark. Deneysel diyabetin sıçan böbreklerinde meydana getirdiği histolojik deği- şiklikler üzerine melatoninin iyileştirici etkileri. İnönü Üniversitesi Tıp Fakültesi Dergisi 2005;12:145-152.
12. 13. Tiedge M, Lortz S, Drinkgern J, et al. Relation between antioxidant enzyme gene expression and antioxidative defense status of insulinproducing cells. Diabetes 1997;46:1733-1742.
13. 14. Ebelt H, Peschke D, Bromme HJ, et al. Influence of melatonin on free radical-induced changes in rat pancreatic beta-cells in vitro. J. Pineal Res 2000;28:65-72.
14. 15. Eşrefoğlu M, Gül M, Ateş B, et al; Antioksidative effect of melatonin, ascorbic acid and N-acetylcysteine on caerulein induced pancreatitis and associated liver injury in rats; World J Gastroenterol 2006;12:259-264.
15. 16. Tresguerres JA, Kireev R, Tresguerres AF, et al. Molecular mechanisms involved in the hormonal prevention of aging in the rat. J Steroid Biochem Mol Biol 2008;108:318-326.
16. 17. Reiter J. Functional pleiotropy of the neurohormone melatonin: antioxidant protection and neuroendocrine regulation. Front Neuroendocrinol 1995;16:383-415.
17. 18. Melchiorri D, Reiter RJ, Attia AM, et al. Potent protective effect of melatonin on in vivo paraquat-induced oxidative damage in rats, Life Sci 1994;56:83-89.
18. 19. Reiter Rj, Tan Dx, Osuna C, Gitto E. Actions of melatonin in the reduction of oxidative stress. J Biomed Sci 2000;7:444- 458.
19. 20. Beyer Ce, Steketee Jd, Saphier D. Antioxidant properties of melatonin-an emerging mystery. Biochem Pharmacol 1998;56:1265-1272.
20. 21. Baynes JW, Thorpe SR Role of oxidative stress in diabetic complications: A new perspective on an old paradigm. Diabetes 1999;48:1-9.
21. 22. Altan N, Ongun CÖ, Hasanoğlu E, et al. effects of the sulfonylurea glyburide on superoxide dismutase activity ın alloxan-ınduced diabetic rat hepatocytes. Diabetes Res Clin Prac 1994;22:95-98.
22. 23. Altan N, Ongun CÖ, Elmalı E, et al. Effects of the Sulfonylurea Glyburide on Glutathione and Glutathione perioxidase activity in Alloxan Induced Diabetic Rat Hepatocytes. Gen Pharma 1994;25:875-887.
23. 24. Saxena AK, Srivastava P, Kale RK, Baquer NZ. Impaired antioxidant status in diabetic rat liver. Effect of vanadate. Biochem Pharma 1993;45 :539-542.
24. 25. Casares FCM, Javier FJP, Collado BJA, et al.; Melatonin reduces apoptosis and necrosis induced by ischemia/reperfusion injury of the pancreas, J Pineal Res 2006;40 :195-203.
25. 26. Elmar Peschke. Melatonin, endocrine pancreas and diabetes. J. Pineal Res 2008;44:26-40
26. 27. Thomas L, Drew JE, Abramovich DR, Williams LM. The role of melatonin in the human fetus (review). Int J Mol Med 1998;1:539-543.
27. 28. Jaworek J, Leja-Szpak A, Bonior J, et al. Protective effect of melatonin and its precursor L- tryptophan on acute pancreatitis induced by caerulein overstimulation or ischemia/reperfusion J Pineal Res 2003;34:40- 52.
28. 29. Kabuto H, Yokoi I, Ogawa N. Melatonin inhibits ironinduced epileptic dischanges in rats by supressing proxidation. Epilepsia 1998;39:237-243.
29. 30. Şener G, Sehirli AO, Satiroğlu H, et al. Melatonin improves oxidative organ damage in a rat model of thermal injury. Burns 2002;28:419-425.
30. 31. Şener G, Tosun O, Sehirli AO, et al. Melatonin and N-acetylcysteine have beneficial effects during hepatic ischemia and reperfusion. Life Sci 2003;72:2707-2718.
31. 32. Şener G, Toklu H, Kapucu C, et al. Melatonin protects against oxidative organ injury in a rat model of sepsis. Surg Today 2005;35:52-59.
32. 33. Kaçmaz A, User EY, Sehirli AO, et al. Protective effect of melatonin against ischemia/ reperfusioninduced oxidative remote organ injury in the rat. Surg Today 2005;35:744-750.
33. 34. Reiter Rj. Antioxidant action of melatonin. Adv Pharmacol 1997;38:103-108.
34. 35. Cevat Y, Kader K. Melatonin: karanlığın antioksidan gücü melatonin. Erciyes Üniversitesi Sağlık Bilimleri Dergisi 2004;13:56-65.
35. 36. Ballı E. Melatoninin fonksiyonları. Mersin Üniversitesi Tıp Fakültesi Dergisi 2003;4:380-385.
36. 37. Vijayalaxmi TCR, Reiter RJ, Herman TS. Melatonin: from basic research to cancer treatment clinics. J Clin Oncology 2002;20:2575- 2601.
37. 38. Kilańczyk E, Bryszewska M. Effect of melatonin on antioxidant enzymes in human diabetic skin. Fıbroblastscellular & Molecular Biology Letters 2003;8:333-336.
38. 39. Fadillioglu E, Kurcer Z, Parlakpinar H, et al. Melatonin treatment against remote organ injury induced by renal ischemia reperfusion injury in diabetes mellitus. Arch Pharm Res 2008 31:705-712.
39. 40. Arendt J. Mammalian pineal rhythms. J Pineal Res 1985;3:161-213.
40. 41. Akıl M. Effect of melatonin administration on lipid peroxidation in the bone tissue of diabetic rats subjected to acute swimming exercise. 11th International Sports Sciences Congress 10-12 October 2010, Antalya.