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Deneysel Diyabet Oluşturulan Sıçanlarda Kalp ve İskelet Kası Nrf2 Yapımı ve Oksidatif Stres Üzerine Melatoninin Etkisinin İncelenmesi

Year 2020, Volume: 4 Issue: 1, 46 - 53, 23.04.2020
https://doi.org/10.25048/tudod.595479

Abstract

Amaç: Diabetes mellitus (DM) kronik hiperglisemi ile karakterize metabolik bir hastalıktır. Bu çalışmanın amacı, melatoninin DM’li
sıçanlarda iskelet kası ve kalp kası üzerindeki etkilerini değerlendirmektir.


Gereç ve Yöntemler: 36 erkek Wistar albino rat kontrol grubu, kontrol + melatonin grubu, Diyabet grubu, Diyabet + melatonin grubu
olarak 4 gruba ayrıldı. Melatonin (10 mg / kg, ip) tedavisi dört hafta süreyle uygulandı. Malondialdehit (MDA) seviyeleri ve indirgenmiş
glutatyon seviyeleri (GSH) ile Nrf2 ve tiyoredoksin (TRX) seviyeleri değerlendirildi.


Bulgular: Diyabetik grubun iskelet ve kalp kası MDA düzeyleri kontrol gruplarına göre yüksek bulunurken, melatonin tedavisi ile bu
değer anlamlı düzeyde azalmıştır (p<0,05). İskelet kası GSH seviyesi melatonin tedavili diyabet grubunda, diyabet grubuna göre yüksek
bulunmuştur. Diyabet grubunda iskelet kası Nrf2 düzeyleri kontrol gruplarına göre azalmıştır. Bu azalış melatonin uygulaması ile
kontrol değerlerine yükselmiştir. Kalp kası Nrf2 düzeyleri diyabet grubunda düşük görülmesine rağmen bu farklılık anlamlı değildir.
İskelet kası TRX seviyelerinde gruplar arasında farklılık saptanmamıştır. Kalp kası TRX seviyeleri diyabetik grupta düşük bulunurken
melatonin tedavisi ile yükselmiştir (p<0,05).


Sonuç: Çalışmamızın sonuçları melatonin tedavisinin hipergliseminin oluşturduğu oksidatif stresi iskelet kasında Nrf2 yolağı ile kalp
kasında ise TRX yolağı ile azaltabileceğini göstermektedir.

Supporting Institution

Zonguldak Bülent Ecevit Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi

Project Number

2016-26259946-02

References

  • Mollazadeh H et al. Effects of pomegranate seed oil on oxidative stress markers, serum biochemical parameters and pathological findings in kidney and heart of streptozotocin-induced diabetic rats. Ren Fail 2016; 38(8): 1256–66.
  • Tian X et al. Resveratrol limits diabetes-associated cognitive decline in rats by preventing oxidative stress and inflammation and modulating hippocampal structural synaptic plasticity. Brain Res 2016; 1650: 1–9.
  • Yang H et al. The protective effects of endogenous hydrogen sulfide modulator, S-propargyl-cysteine, on high glucose-induced apoptosis in cardiomyocytes: A novel mechanism mediated by the activation of Nrf2. Eur J Pharmacol 2015; 761: 135–43.
  • Chen J et al. Diabetic cardiomyopathy and its prevention by Nrf2: Current status. Diabetes Metab J 2014; 38(5): 337–45.
  • Guan Y et al. Celastrol attenuates oxidative stress in the skeletal muscle of diabetic rats by regulating the AMPK-PGC1α-SIRT3 signaling pathway. Int J Mol Med 2016; 37(5): 1229–38.
  • Cappellari GG et al. Unacylated ghrelin reduces skeletal muscle reactive oxygen species generation and inflammation and prevents high-fat diet-induced hyperglycemia and whole-body insulin resistance in rodents. Diabetes 2016; 65(4): 874–86.
  • Boden MJ et al. Overexpression of manganese superoxide dismutase ameliorates high-fat diet-induced insulin resistance in rat skeletal muscle. Am J Physiol Metab 2012; 303(6): E798–805.
  • Wu H, Ballantyne CM. Skeletal muscle inflammation and insulin resistance in obesity. J Clin Invest 2017; 127(1): 43–54.
  • D’Souza DM et al. Diabetic myopathy: Impact of diabetes mellitus on skeletal muscle progenitor cells. Frontiers in Physiology 2013; 4: 374.
  • Liu YW et al. Mangiferin Upregulates Glyoxalase 1 Through Activation of Nrf2/ARE Signaling in Central Neurons Cultured with High Glucose. Mol Neurobiol 2017; 54(6): 4060–70.
  • Sun Q et al. The role of DJ-1/Nrf2 pathway in the pathogenesis of diabetic nephropathy in rats. Ren Fail 2016; 38(2): 294–304.
  • Reiter RJ et al. Melatonin as an antioxidant: under promises but over delivers. J Pineal Res 2016; 61(3): 253–78.
  • Teodoro BG et al. Melatonin prevents mitochondrial dysfunction and insulin resistance in rat skeletal muscle. J Pineal Res 2014; 57(2): 155–67.
  • Jiang T et al. Protective Effects of Melatonin on Retinal Inflammation and Oxidative Stress in Experimental Diabetic Retinopathy. Oxid Med Cell Longev2016; 2016: 1–13.
  • Casini AF et al. Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene-intoxicated mice. Am J Pathol 1986; 123(3): 520–31.
  • Aykaç G et al. The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. Toxicology 1986; 36(1): 71–6.
  • Meng S et al. Silymarin ameliorates diabetic cardiomyopathy via inhibiting TGF-β1/Smad signaling. Cell Biol Int 2019; 43(1): 65–72.
  • Marwick TH et al. Implications of Underlying Mechanisms for the Recognition and Management of Diabetic Cardiomyopathy. Journal of the American College of Cardiology 2018; 71(3): 339-351.
  • Ge Z-D et al. Current Status and Challenges of NRF2 as a Potential Therapeutic Target for Diabetic Cardiomyopathy. Int Heart J 2019; 60(3): 512-520.
  • Trachanas K et al. Diabetic cardiomyopathy: From pathophysiology to treatment. Hellenic Journal of Cardiology 2014; 55(5): 411-421.
  • Kandemir Y et al. Melatonin protects against streptozotocin-induced diabetic cardiomyopathy through the mammalian target of rapamycin (mTOR) signaling pathway. Adv Clin Exp Med 2019; 28(9):0–0.
  • Jia G et al. Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy. Nature Reviews Endocrinology 2016; 12(3): 144–153.
  • Fuentes-Antras J et al. Updating experimental models of diabetic cardiomyopathy. J Diabetes Res 2015:656795.
  • Hernández-Ochoa EO et al. The Underlying Mechanisms of Diabetic Myopathy. J Diabetes Res 2017:1–3.
  • Maritim AC et al. Diabetes, oxidative stress, and antioxidants: A review. J Biochem Mol Toxicol 2003; 17(1): 24–38.
  • Soliman GZ. Blood lipid peroxidation (superoxide dismutase, malondialdehyde, glutathione) levels in Egyptian type 2 diabetic patients. Singapore Med J 2008;Feb;49(2): 129-36.
  • Armstrong AM et al. The effect of dietary treatment on lipid peroxidation and antioxidant status in newly diagnosed noninsulin dependent diabetes. Free Radic Biol Med 1996; 21(5): 719–26.
  • Tan DX et al. Melatonin as a potent and inducible endogenous antioxidant: Synthesis and metabolism. Molecules 2015; 20(10): 18886–906.
  • Reiter RJ et al. Reducing oxidative/nitrosative stress: A newly-discovered genre for melatonin melatonin as an antioxidant. Critical Reviews in Biochemistry and Molecular Biology 2009; 44(4): 175-200.
  • Bonnefont-Rousselot D, Collin F. Melatonin: Action as antioxidant and potential applications in human disease and aging. Toxicology 2010; 278(1): 55–67.
  • Onk D et al. Effect of melatonin on antioxidant capacity, inflammation and apoptotic cell death in lung tissue of diabetic rats. Acta Cir Bras 2018; 33(4): 375–85.
  • Bicer M et al. Melatonin has a protective effect against lipid peroxidation in the bone tissue of diabetic rats subjected to acute swimming exercise. Hormone Molecular Biology and Clinical Investigation 2018; 34(2).
  • Mehrzadi S et al. Protective effect of melatonin in the diabetic rat retina. Fundam Clin Pharmacol 2018; 32(4): 414–21.
  • Rodriguez C et al. Regulation of antioxidant enzymes: A significant role for melatonin. J Pineal Res 2004; 36(1): 1–9.
  • Uruno A et al. The Keap1-Nrf2 system and diabetes mellitus. Archives of Biochemistry and Biophysics 2015; 566: 76-84.
  • Coleman V et al. Partial involvement of Nrf2 in skeletal muscle mitohormesis as an adaptive response to mitochondrial uncoupling. Sci Rep 2018; 8(1): 2446.
  • Shi S et al. Melatonin attenuates acute kidney ischemia/reperfusion injury in diabetic rats by activation of the SIRT1/Nrf2/HO-1 signaling pathway. Biosci Rep 2019; 39(1): BSR20181614.
  • Negi G et al. Melatonin modulates neuroinflammation and oxidative stress in experimental diabetic neuropathy: Effects on NF-κB and Nrf2 cascades. J Pineal Res 2011; 50(2): 124–31.
  • He X et al. Nrf2 is critical in defense against high glucose-induced oxidative damage in cardiomyocytes. J Mol Cell Cardiol 2009; 46(1): 47–58.
  • Ding K et al. Melatonin stimulates antioxidant enzymes and reduces oxidative stress in experimental traumatic brain injury: The Nrf2-ARE signaling pathway as a potential mechanism. Free Radic Biol Med 2014; 73: 1–11.
  • Zhang Y et al. Melatonin protects H9c2 cells against ischemia/reperfusion-induced apoptosis and oxidative stress via activation of the Nrf2 signaling pathway. Mol Med Rep 2018; 18(3): 3497–505.
  • Liu Y et al. Melatonin improves cardiac function in a mouse model of heart failure with preserved ejection fraction. Redox Biol 2018; 18: 211–21.
  • Okatan EN et al. Cardioprotective effect of selenium via modulation of cardiac ryanodine receptor calcium release channels in diabetic rat cardiomyocytes through thioredoxin system. J Nutr Biochem 2013; 24(12): 2110–2118.
  • Li H et al. Thioredoxin 2 offers protection against mitochondrial oxidative stress in H9c2 cells and against myocardial hypertrophy induced by hyperglycemia. Int J Mol Sci 2017; 18(9): 1958.
  • Schulze PC et al. Hyperglycemia promotes oxidative stress through inhibition of thioredoxin function by thioredoxin-interacting protein. J Biol Chem 2004; 279(29): 30369–74.
  • Yu L et al. Melatonin rescues cardiac thioredoxin system during ischemia-reperfusion injury in acute hyperglycemic state by restoring Notch1/Hes1/Akt signaling in a membrane receptor-dependent manner. J Pineal Res 2017; 62(1): e12375.

The Effects of Melatonin on Nrf2 Expression and Oxidative Stress in Heart Muscle and Skeletal Muscle in Rats with Experimental Diabetes

Year 2020, Volume: 4 Issue: 1, 46 - 53, 23.04.2020
https://doi.org/10.25048/tudod.595479

Abstract

Aim: Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycemia. The goal of this study was to assess the effects of melatonin on skeletal muscle and heart muscle in rats with DM.


Material and Methods: 36 male Wistar albino rats were divided into 4 groups as control group, control+melatonin group, Diabetes group, Diabetes+melatonin group. Melatonin (10 mg/kg, ip) treatment was administered for four weeks. Malondialdehyde (MDA) level, reduced glutathione levels (GSH), Nrf2 and thioredoxin (TRX) levels were assessed.


Results: Skeletal and heart muscle MDA levels of the diabetic group were increased than the control groups and melatonin treatment was remarkably decreased this value. (p<0.05). Skeletal muscle GSH levels in the melatonin treated diabetic group was significantly higher than the diabetic group. In the diabetic group, skeletal muscle Nrf2 levels were found lower than control groups. This value increased to control levels with Melatonin treatment. Nrf2 levels of heart muscle in the diabetes group was found to be decreased, but grupit was not statistically significant. There was no differences between the groups in skeletal muscle in TRX levels. In the diabetes group, heart muscle TRX levels were lower than control groups and melatonin treatment increased this level (p<0.05).

Conclusion: Our results showed that melatonin treatment can reduce the oxidative stress induced with hyperglycemia by Nrf2 pathway in skeletal muscle and by TRX pathway in cardiac muscle.


Project Number

2016-26259946-02

References

  • Mollazadeh H et al. Effects of pomegranate seed oil on oxidative stress markers, serum biochemical parameters and pathological findings in kidney and heart of streptozotocin-induced diabetic rats. Ren Fail 2016; 38(8): 1256–66.
  • Tian X et al. Resveratrol limits diabetes-associated cognitive decline in rats by preventing oxidative stress and inflammation and modulating hippocampal structural synaptic plasticity. Brain Res 2016; 1650: 1–9.
  • Yang H et al. The protective effects of endogenous hydrogen sulfide modulator, S-propargyl-cysteine, on high glucose-induced apoptosis in cardiomyocytes: A novel mechanism mediated by the activation of Nrf2. Eur J Pharmacol 2015; 761: 135–43.
  • Chen J et al. Diabetic cardiomyopathy and its prevention by Nrf2: Current status. Diabetes Metab J 2014; 38(5): 337–45.
  • Guan Y et al. Celastrol attenuates oxidative stress in the skeletal muscle of diabetic rats by regulating the AMPK-PGC1α-SIRT3 signaling pathway. Int J Mol Med 2016; 37(5): 1229–38.
  • Cappellari GG et al. Unacylated ghrelin reduces skeletal muscle reactive oxygen species generation and inflammation and prevents high-fat diet-induced hyperglycemia and whole-body insulin resistance in rodents. Diabetes 2016; 65(4): 874–86.
  • Boden MJ et al. Overexpression of manganese superoxide dismutase ameliorates high-fat diet-induced insulin resistance in rat skeletal muscle. Am J Physiol Metab 2012; 303(6): E798–805.
  • Wu H, Ballantyne CM. Skeletal muscle inflammation and insulin resistance in obesity. J Clin Invest 2017; 127(1): 43–54.
  • D’Souza DM et al. Diabetic myopathy: Impact of diabetes mellitus on skeletal muscle progenitor cells. Frontiers in Physiology 2013; 4: 374.
  • Liu YW et al. Mangiferin Upregulates Glyoxalase 1 Through Activation of Nrf2/ARE Signaling in Central Neurons Cultured with High Glucose. Mol Neurobiol 2017; 54(6): 4060–70.
  • Sun Q et al. The role of DJ-1/Nrf2 pathway in the pathogenesis of diabetic nephropathy in rats. Ren Fail 2016; 38(2): 294–304.
  • Reiter RJ et al. Melatonin as an antioxidant: under promises but over delivers. J Pineal Res 2016; 61(3): 253–78.
  • Teodoro BG et al. Melatonin prevents mitochondrial dysfunction and insulin resistance in rat skeletal muscle. J Pineal Res 2014; 57(2): 155–67.
  • Jiang T et al. Protective Effects of Melatonin on Retinal Inflammation and Oxidative Stress in Experimental Diabetic Retinopathy. Oxid Med Cell Longev2016; 2016: 1–13.
  • Casini AF et al. Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene-intoxicated mice. Am J Pathol 1986; 123(3): 520–31.
  • Aykaç G et al. The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. Toxicology 1986; 36(1): 71–6.
  • Meng S et al. Silymarin ameliorates diabetic cardiomyopathy via inhibiting TGF-β1/Smad signaling. Cell Biol Int 2019; 43(1): 65–72.
  • Marwick TH et al. Implications of Underlying Mechanisms for the Recognition and Management of Diabetic Cardiomyopathy. Journal of the American College of Cardiology 2018; 71(3): 339-351.
  • Ge Z-D et al. Current Status and Challenges of NRF2 as a Potential Therapeutic Target for Diabetic Cardiomyopathy. Int Heart J 2019; 60(3): 512-520.
  • Trachanas K et al. Diabetic cardiomyopathy: From pathophysiology to treatment. Hellenic Journal of Cardiology 2014; 55(5): 411-421.
  • Kandemir Y et al. Melatonin protects against streptozotocin-induced diabetic cardiomyopathy through the mammalian target of rapamycin (mTOR) signaling pathway. Adv Clin Exp Med 2019; 28(9):0–0.
  • Jia G et al. Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy. Nature Reviews Endocrinology 2016; 12(3): 144–153.
  • Fuentes-Antras J et al. Updating experimental models of diabetic cardiomyopathy. J Diabetes Res 2015:656795.
  • Hernández-Ochoa EO et al. The Underlying Mechanisms of Diabetic Myopathy. J Diabetes Res 2017:1–3.
  • Maritim AC et al. Diabetes, oxidative stress, and antioxidants: A review. J Biochem Mol Toxicol 2003; 17(1): 24–38.
  • Soliman GZ. Blood lipid peroxidation (superoxide dismutase, malondialdehyde, glutathione) levels in Egyptian type 2 diabetic patients. Singapore Med J 2008;Feb;49(2): 129-36.
  • Armstrong AM et al. The effect of dietary treatment on lipid peroxidation and antioxidant status in newly diagnosed noninsulin dependent diabetes. Free Radic Biol Med 1996; 21(5): 719–26.
  • Tan DX et al. Melatonin as a potent and inducible endogenous antioxidant: Synthesis and metabolism. Molecules 2015; 20(10): 18886–906.
  • Reiter RJ et al. Reducing oxidative/nitrosative stress: A newly-discovered genre for melatonin melatonin as an antioxidant. Critical Reviews in Biochemistry and Molecular Biology 2009; 44(4): 175-200.
  • Bonnefont-Rousselot D, Collin F. Melatonin: Action as antioxidant and potential applications in human disease and aging. Toxicology 2010; 278(1): 55–67.
  • Onk D et al. Effect of melatonin on antioxidant capacity, inflammation and apoptotic cell death in lung tissue of diabetic rats. Acta Cir Bras 2018; 33(4): 375–85.
  • Bicer M et al. Melatonin has a protective effect against lipid peroxidation in the bone tissue of diabetic rats subjected to acute swimming exercise. Hormone Molecular Biology and Clinical Investigation 2018; 34(2).
  • Mehrzadi S et al. Protective effect of melatonin in the diabetic rat retina. Fundam Clin Pharmacol 2018; 32(4): 414–21.
  • Rodriguez C et al. Regulation of antioxidant enzymes: A significant role for melatonin. J Pineal Res 2004; 36(1): 1–9.
  • Uruno A et al. The Keap1-Nrf2 system and diabetes mellitus. Archives of Biochemistry and Biophysics 2015; 566: 76-84.
  • Coleman V et al. Partial involvement of Nrf2 in skeletal muscle mitohormesis as an adaptive response to mitochondrial uncoupling. Sci Rep 2018; 8(1): 2446.
  • Shi S et al. Melatonin attenuates acute kidney ischemia/reperfusion injury in diabetic rats by activation of the SIRT1/Nrf2/HO-1 signaling pathway. Biosci Rep 2019; 39(1): BSR20181614.
  • Negi G et al. Melatonin modulates neuroinflammation and oxidative stress in experimental diabetic neuropathy: Effects on NF-κB and Nrf2 cascades. J Pineal Res 2011; 50(2): 124–31.
  • He X et al. Nrf2 is critical in defense against high glucose-induced oxidative damage in cardiomyocytes. J Mol Cell Cardiol 2009; 46(1): 47–58.
  • Ding K et al. Melatonin stimulates antioxidant enzymes and reduces oxidative stress in experimental traumatic brain injury: The Nrf2-ARE signaling pathway as a potential mechanism. Free Radic Biol Med 2014; 73: 1–11.
  • Zhang Y et al. Melatonin protects H9c2 cells against ischemia/reperfusion-induced apoptosis and oxidative stress via activation of the Nrf2 signaling pathway. Mol Med Rep 2018; 18(3): 3497–505.
  • Liu Y et al. Melatonin improves cardiac function in a mouse model of heart failure with preserved ejection fraction. Redox Biol 2018; 18: 211–21.
  • Okatan EN et al. Cardioprotective effect of selenium via modulation of cardiac ryanodine receptor calcium release channels in diabetic rat cardiomyocytes through thioredoxin system. J Nutr Biochem 2013; 24(12): 2110–2118.
  • Li H et al. Thioredoxin 2 offers protection against mitochondrial oxidative stress in H9c2 cells and against myocardial hypertrophy induced by hyperglycemia. Int J Mol Sci 2017; 18(9): 1958.
  • Schulze PC et al. Hyperglycemia promotes oxidative stress through inhibition of thioredoxin function by thioredoxin-interacting protein. J Biol Chem 2004; 279(29): 30369–74.
  • Yu L et al. Melatonin rescues cardiac thioredoxin system during ischemia-reperfusion injury in acute hyperglycemic state by restoring Notch1/Hes1/Akt signaling in a membrane receptor-dependent manner. J Pineal Res 2017; 62(1): e12375.
There are 46 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Research Article
Authors

Salim Özenoğlu This is me 0000-0002-1911-269X

İnci Turan 0000-0003-2211-3914

Hale Sayan Özaçmak 0000-0002-3564-0468

Veysel Haktan Özaçmak 0000-0003-2651-8353

Project Number 2016-26259946-02
Publication Date April 23, 2020
Acceptance Date April 22, 2020
Published in Issue Year 2020 Volume: 4 Issue: 1

Cite

APA Özenoğlu, S., Turan, İ., Sayan Özaçmak, H., Özaçmak, V. H. (2020). Deneysel Diyabet Oluşturulan Sıçanlarda Kalp ve İskelet Kası Nrf2 Yapımı ve Oksidatif Stres Üzerine Melatoninin Etkisinin İncelenmesi. Türkiye Diyabet Ve Obezite Dergisi, 4(1), 46-53. https://doi.org/10.25048/tudod.595479
AMA Özenoğlu S, Turan İ, Sayan Özaçmak H, Özaçmak VH. Deneysel Diyabet Oluşturulan Sıçanlarda Kalp ve İskelet Kası Nrf2 Yapımı ve Oksidatif Stres Üzerine Melatoninin Etkisinin İncelenmesi. Turk J Diab Obes. April 2020;4(1):46-53. doi:10.25048/tudod.595479
Chicago Özenoğlu, Salim, İnci Turan, Hale Sayan Özaçmak, and Veysel Haktan Özaçmak. “Deneysel Diyabet Oluşturulan Sıçanlarda Kalp Ve İskelet Kası Nrf2 Yapımı Ve Oksidatif Stres Üzerine Melatoninin Etkisinin İncelenmesi”. Türkiye Diyabet Ve Obezite Dergisi 4, no. 1 (April 2020): 46-53. https://doi.org/10.25048/tudod.595479.
EndNote Özenoğlu S, Turan İ, Sayan Özaçmak H, Özaçmak VH (April 1, 2020) Deneysel Diyabet Oluşturulan Sıçanlarda Kalp ve İskelet Kası Nrf2 Yapımı ve Oksidatif Stres Üzerine Melatoninin Etkisinin İncelenmesi. Türkiye Diyabet ve Obezite Dergisi 4 1 46–53.
IEEE S. Özenoğlu, İ. Turan, H. Sayan Özaçmak, and V. H. Özaçmak, “Deneysel Diyabet Oluşturulan Sıçanlarda Kalp ve İskelet Kası Nrf2 Yapımı ve Oksidatif Stres Üzerine Melatoninin Etkisinin İncelenmesi”, Turk J Diab Obes, vol. 4, no. 1, pp. 46–53, 2020, doi: 10.25048/tudod.595479.
ISNAD Özenoğlu, Salim et al. “Deneysel Diyabet Oluşturulan Sıçanlarda Kalp Ve İskelet Kası Nrf2 Yapımı Ve Oksidatif Stres Üzerine Melatoninin Etkisinin İncelenmesi”. Türkiye Diyabet ve Obezite Dergisi 4/1 (April 2020), 46-53. https://doi.org/10.25048/tudod.595479.
JAMA Özenoğlu S, Turan İ, Sayan Özaçmak H, Özaçmak VH. Deneysel Diyabet Oluşturulan Sıçanlarda Kalp ve İskelet Kası Nrf2 Yapımı ve Oksidatif Stres Üzerine Melatoninin Etkisinin İncelenmesi. Turk J Diab Obes. 2020;4:46–53.
MLA Özenoğlu, Salim et al. “Deneysel Diyabet Oluşturulan Sıçanlarda Kalp Ve İskelet Kası Nrf2 Yapımı Ve Oksidatif Stres Üzerine Melatoninin Etkisinin İncelenmesi”. Türkiye Diyabet Ve Obezite Dergisi, vol. 4, no. 1, 2020, pp. 46-53, doi:10.25048/tudod.595479.
Vancouver Özenoğlu S, Turan İ, Sayan Özaçmak H, Özaçmak VH. Deneysel Diyabet Oluşturulan Sıçanlarda Kalp ve İskelet Kası Nrf2 Yapımı ve Oksidatif Stres Üzerine Melatoninin Etkisinin İncelenmesi. Turk J Diab Obes. 2020;4(1):46-53.

Turkish Journal of Diabetes and Obesity (Turk J Diab Obes) is a scientific publication of Zonguldak Bulent Ecevit University Obesity and Diabetes Research and Application Center.

This is a refereed journal, which is published in printed and electronic forms. It aims at achieving free knowledge to the related national and international organizations and individuals.

This journal is published annually three times (in April, August and December).

The publication language of the journal is Turkish and English.