Diyabetik Sıçanlarda Melatonin Uygulamasının Karaciğer, Böbrek, Mide, Pankreas ve Göz Dokularında Oksidatif Stres Üzerine Etkisi

Year 2017, Volume: 1 Issue: 3, 117 - 123, 03.12.2017

Meryem Ergenç Salim Özenoğlu İnci Turan Veysel Haktan Özaçmak Hale Sayan Özaçmak

Abstract

Amaç: Oksidatif stresin diyabetik komplikasyonların gelişiminde çok önemli rol oynadığı yaygın olarak kabul edilmektedir. Böylece koruyucu tedaviler hastalığın olası yan etkilerini hafifletebilir. Bu çalışmanın amacı melatonin tedavisinin diyabetik sıçanların karaciğer, böbrek, pankreas, mide ve retinal dokularındaki oksidan ve antioksidan durumuna etkisini incelemektir.

Gereç ve Yöntemler: Erkek Wistar albino cinsi sıçanlar 4 gruba ayrıldılar: Kontrol, kontrol+melatonin, diyabetik ve diyabet+melatonin uygulanan grup. Sıçanlarda intraperitoneal (i.p) olarak tek doz streptozotosin (STZ) (60 mg/kg) uygulaması ile diyabet oluşturulmuştur. Melatonin 10 mg/kg dozunda günde tek doz i.p olarak 30 gün boyunca uygulanmıştır. 30 günlük tedavinin sonunda indirgenmiş glutatyon (GSH) ve malondialdehid (MDA) düzeyleri karaciğer, böbrek, pankreas, mide ve retinada ölçülmüştür.

Bulgular: Sonuçlarımız diyabetik hayvanların dokularında MDA düzeylerinin arttığını ve GSH seviyelerinin azaldığını göstermiştir. Melatonin uygulaması karaciğer dışındaki dokularda MDA düzeylerini anlamlı olarak düşürmüştür. Melatonin tedavisi diyabet grubuna göre karşılaştırıldığında GSH düzeylerinde pankreas ve mide dışındaki dokularda artış bulunmuştur.

Sonuç: Bu çalışmada sunulan sonuçlar, diyabete, diyabetik komplikasyonların başlıca nedeni olarak kabul edilen oksidatif stresin eşlik ettiği ortak görüşüyle uyumludur. Sonuçlarımız melatoninin diyabette artan oksidatif stres üzerinde iyileştirici etkisi ile kullanılabileceğini göstermektedir.

Keywords

Diabetes mellitüs, Melatonin, Oksidatif stres, Glutatyon

The Effect of Melatonin Administration in Diabetic Rats on Oxidative Stress in Liver, Kidney, Stomach, Pancreas and Eye Tissues

Abstract

Aim: It is commonly accepted that oxidative stress plays a crucial role in the development of diabetic complication. Thus, preventive therapy can alleviate the possible side effects of the disease. The aim of the present study was to investigate the effect of melatonin administration on the oxidant and antioxidant system in the liver, kidney, pancreas, stomach and retinal tissues of diabetic rats.

Material and Methods: Male Wistar albino rats were randomly divided into 4 groups: control; control+Melatonin treatment; diabetic; diabetic+melatonin treatment. Rats were injected with a single intraperitoneal (i.p) injection of streptozotocin (STZ) (60 mg/kg) to induce diabetes mellitus. Melatonin (10 mg/kg) was given daily by i.p injection for 30 days. After 30 days of treatment, the contents of reduced glutathione (GSH) and malondialdehyde (MDA) in liver, kidney, pancreas, stomach and retina were assayed.

Results: Our results showed that diabetic rats exhibited significant decreases in GSH level and exhibited a high level of MDA in tissues. Melatonin treatment significantly reduced the elevated MDA level all tissues except liver tissue. GSH levels were found to increase in all tissues except pancreas and stomach after melatonin treatment compared diabetes group.

Conclusion: The results presented in this study are in agreement with the common view that diabetes is accompanied by oxidative stress, which is regarded as the main cause of diabetic complications. Our results suggests that melatonin could be used for its ameliorative effect against oxidative stress in diabetes

Keywords

Diabetes mellitus, Melatonin, Oxidative stress, Glutathione

References

• 1. Sheweita SA, Mashaly S, Newairy AA, Abdou HM, Eweda SM. Changes in Oxidative Stress and Antioxidant Enzyme Activities in Streptozotocin-Induced Diabetes Mellitus in Rats: Role of Alhagi maurorum Extracts. Oxid Med Cell Longev. 2016; 2016:1-8 5264064.
• 2. Giugliano D, Ceriello A, Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care. 1996; 19: 257– 267.
• 3. Abdulmonim A Alqasim, Essam Eldin M Noureldin, Sami H Hammadi, Ghada E Esheba. Effect of melatonin versus vitamin D as antioxidant and Hepatoprotective agents in STZinduced diabetic rats. J. Diabetes Metab. Disord. 2017; 16: 41.
• 4. Yilmaz-Ozden T, Kurt-Sirin O, Tunali S, Akev N, Can A, Yanardag R. Ameliorative effect of vanadium on oxidative stress in stomach tissue of diabetic rats. Bosn. J. Basic Med. Sci. 2014; 14: 105-109.
• 5. Xu L, Li Z, Guo F. Curcumin improves expression of ghrelin through attenuating oxidative stress in gastric tissues of streptozotocin-induced diabetic gastroparesis rats. Eur. J. Pharmacol. 2013; 718: 219-225.
• 6. Onk D, Onk OA, Turkmen K, Erol HS, Ayazoglu TA, Keles ON, Halici M, Topal E. Melatonin Attenuates Contrast-Induced Nephropathy in Diabetic Rats: The Role of Interleukin-33 and Oxidative Stress. Mediators Inflamm. 2016; 2016: 1-20.
• 7. Derlacz RA, Sliwinska M, Piekutowska A, Winiarska K, Drozak J, Bryla J. Melatonin is more effective than taurine and 5-hydroxytryptophan against hyperglycemia-induced kidneycortex tubules injury. J. Pineal Res. 2007; 42: 203-209.
• 8. Zhang J, Yang S, Li H, Chen F, Shi J. Naringin ameliorates diabetic nephropathy by inhibiting NADPH oxidase 4. Eur. J. Pharmacol. 2017; 804: 1-6.
• 9. Al-Dosari DI, Ahmed MM, Al-Rejaie SS, Alhomida AS, Ola MS. Flavonoid Naringenin Attenuates Oxidative Stress, Apoptosis and Improves Neurotrophic Effects in the Diabetic Rat Retina. Nutrients. 2017; 9: E1161.
• 10. Kumar B, Gupta SK, Nag TC, Srivastava S, Saxena R, Jha KA, Srinivasan BP. Retinal neuroprotective effects of quercetin in streptozotocin-induced diabetic rats. Exp Eye Res. 2014; 125: 193-202.
• 11. Jiang T, Chang Q, Cai J, Fan J, Zhang X, Xu G. Protective Effects of Melatonin on Retinal Inflammation and Oxidative Stress in Experimental Diabetic Retinopathy. Oxid. Med. Cell Longev. 2016; 2016: 1-13.
• 12. Allagui MS, Feriani A, Bouoni Z, Alimi H, Murat JC, El Feki A. Protective effects of vitamins (C and E) and melatonin coadministration on hematological and hepatic functions and oxidative stress in alloxan-induced diabetic rats. J Physiol. Biochem. 2014; 70: 713-723.
• 13. Casini A, Ferrali M, Pampella A, Maellaro E, Comporti M. Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene-intoxicated mice. Am J Pathol. 1986; 123: 520-531.
• 14. Aykac G, Uysal M, Yalan AS, et al. The effects of chronic ethanol injection on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. Toxicology 1985; 36:71-76.
• 15. Montilla PL, Vargas JF, Tunez IF, Muñoz de Agueda MC, Valdelvira ME, Cabrera ES. Oxidative stress in diabetic rats induced by streptozotocin: protective effects of melatonin. J Pineal Res. 1998; 25: 94–100.
• 16. Dominguez C, Ruiz E, Gussinye M, Carrascosa A. Oxidative stress at onset and in early stages of type 1 diabetes in children and adolescents. Diabetes Care 1998; 21: 1736–1742.
• 17. Meral I, Yener Z, Kahraman T, Mert N. Effect of Nigella sativa on glucose concentration, lipid peroxidation, anti-oxidant defence system and liver damage in experimentally-induced diabetic rabbits. J Vet Med A Physiol Pathol Clin Med. 2001; 48: 593–599.
• 18. Aksoy N, Vural H, Sabuncu T, Aksoy S. Effects of melatonin on oxidative-antioxidative status of tissues in streptozotocininduced diabetic rats. Cell Biochem Funct. 2003; 21: 121–125.
• 19. Baydas G, Reiter RJ, Yasar A, Tuzcu M, Akdemir I, Nedzvetskii VS. Melatonin reduces glial reactivity in the hippocampus, cortex, and cerebellum of streptozotocin-induced diabetic rats. Free Radic Biol Med. 2003; 35: 797–804.
• 20. Winiarska K, Fraczyk T, Malinska D, Drozak J, Bryla J. Melatonin attenuates diabetes-induced oxidative stress in rabbits. J Pineal Res. 2006; 40: 168-176.
• 21. Gobbo MG, Costa CF, Silva DG, de Almeida EA, Góes RM. Effect of Melatonin Intake on Oxidative Stress Biomarkers in Male Reproductive Organs of Rats under Experimental Diabetes. Oxid Med Cell Longev. 2015; 2015: 1-11
• 22. Elbe H, Esrefoglu M, Vardi N, Taslidere E, Ozerol E, Tanbek K. Melatonin, quercetin and resveratrol attenuates oxidative hepatocellular injury in streptozotocin-induced diabetic rats.Hum Exp Toxicol. 2015; 34: 859-868.
• 23. Yanardag R, Ozsoy-Sacan O, Bolkent S, Orak H, Karabulut- Bulan O. Protective effects of metformin treatment on the liver injury of streptozotocin-diabetic rats. Human Exp Toxicol. 2005; 24: 129
• 24. Guven A, Yavuz O, Cam M, Ercan F, Bukan N, Comunoglu C, Gokce F. Effects of melatonin on streptozotocin-induced diabetic liver injury in rats. Acta Histochemica. 2006; 108: 85–93.
• 25. Korkmaz GG, Uzun H, Cakatay U, Aydin S. Melatonin ameliorates oxidative damage in hyperglycemia-induced liver injury. Clin Invest Med. 2012; 35: 370–377.
• 26. Cam M, Yavuz O, Guven A, Ercan F, Bukan N, Ustundag N. Protective effects of chronic melatonin treatment against renal injury in streptozotocin-induced diabetic rats. J Pineal Res. 2003; 35: 212-220
• 27. Oktem F, Ozguner F, Yilmaz HR, Uz E, Dündar B. Melatonin reduces urinary excretion of N-acetyl-beta-D-glucosaminidase, albumin and renal oxidative markers in diabetic rats. Clin Exp Pharmacol Physiol. 2006; 33: 95-101.
• 28. Tosini G, Menaker M. The clock in the mouse retina: melatonin synthesis and photoreceptor degeneration. Brain Research. 1998; 789: 221–228.
• 29. do Carmo Buonfiglio D, Peliciari-Garcia RA, do Amaral FG, Peres R, Nogueira TC, Afeche SC, Cipolla-Neto J. Early-stage retinal melatonin synthesis impairment in streptozotocininduced diabetic wistar rats. Investigative Ophthalmology and Visual Science. 2011; 52: 7416–7422.
• 30. Gürpinar T, Ekerbiçer N, Uysal N, Barut T, Tarakçi F, Tuglu MI. The effects of the melatonin treatment on the oxidative stress and apoptosis in diabetic eye and brain. The Scientific World Journal. 2012; 2012: 1-5.
• 31. Bathina S, Srinivas N, Das UN. Streptozotocin produces oxidative stress, inflammation and decreases BDNF concentrations to induce apoptosis of RIN5F cells and type 2 diabetes mellitus in Wistar rats. Biochem Biophys Res Commun. 2017; 486: 406-413.
• 32. Yavuz O, Cam M, Bukan N, Guven A, Silan F. Protective effect of melatonin on beta-cell damage in streptozotocin-induced diabetes in rats. Acta Histochem. 2003; 105: 261-266.
• 33. Coskun ZM, Sacan O, Karatug A, Turk N, Yanardag R, Bolkent S, Bolkent S. Regulation of oxidative stress and somatostatin, cholecysto-kinin, apelin gene expressions by ghrelin in stomach of newborn diabetic rats. Acta Histochem. 2013; 115: 740–747.
• 34. Pradeepkumar Singh L, Vivek Sharma A, Swarnakar S. Upregulation of collagenase-1 and -3 in indomethacininduced gastric ulcer in diabetic rats: role of melatonin. J Pineal Res. 2011; 51(1):61-74.
• 35. Grigorov I, Bogojević D, Jovanović S, Petrović A, Ivanović- Matić S, Zolotarevski L, Poznanović G, Martinović V. Hepatoprotective effects of melatonin against pronecrotic cellular events in streptozotocin-induced diabetic rats. J Physiol Biochem. 2014; 70: 441-450.