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Streptozotosin ile İndüklenmiş Diyabetik Sıçanlarda Melatoninin Antioksidan Aktivitesi; Kan ve Karaciğer Dokusunda

Year 2020, Volume: 10 Issue: 4, 608 - 614, 15.12.2020
https://doi.org/10.31832/smj.787622

Abstract

AMAÇ: Bu çalışmada Streptozotosin (STZ) ile deneysel tip 1 diyabet oluşturulan sıçanların kan ve karaciğer dokularında oluşan oksidatif hasara karşı melatonin takviyesinin koruyucu etkisinin araştırılması amaçlandı.
GEREÇ ve YÖNTEM: Kırk adet yetişkin Spraque Dawley erkek sıçan; grup 1- kontrol grubu, grup 2-diyabet oluşturulan grup, grup 3- melatonin takviye grubu ve grup 4- diyabet ve melatonin takviye grubu olmak üzere dört gruba ayrıldı. Sıçanlara tek doz 60 mg/kg STZ İntraperitoneal (i.p.) olarak uygulanması ile diyabet oluşturuldu. Melatonin takviyesi ise 10 mg/kg/gün dozunda subkutan olarak (s.c.) 6 hafta boyunca uygulandı. Deney sonunda alınan karaciğer ve serum örneklerinde; glutatyon (GSH), katalaz (CAT) ve malondialdehit (MDA) düzeyleri spektrofotometrik yöntem kullanılarak ölçüldü.
BULGULAR: Çalışma sonuçları diyabetik hayvanların serum ve karaciğer dokularında MDA düzeylerinin arttığını gösterdi. Melatonin uygulamasının her iki dokuda da MDA düzeylerini azaltıp, GSH ve CAT düzeylerini artırdığı veya düşmesini engelleyerek kararlı bir şekilde kalmasını sağladığı görüldü (p< 0,05).
SONUÇ: Bu çalışma sonuçları, diyabetin komplikasyonlarının temel nedenlerinden birinin de oksidatif stres olduğunu vurgulayan ve kabul eden ortak görüşle uyumludur. Sonuçlarımız melatoninin diyabette artan oksidatif stres üzerinde iyileştirici etkisinin bulunduğunu ve melatoninin terapötik bir ajan olarak kullanılabileceğini göstermektedir.

Supporting Institution

Sakarya Üniversitesi

Project Number

2018-08-06-001

References

  • KAYNAKLAR 1. Matough FA, Budin SB, Hamid ZA, Alwahaibi N, Mohamed J. The role of oxidative stress and antioxidants in diabetic complications. Sultan Qaboos University Medical Journal 2012;12(1):1-5.
  • 2. El Faramawy SM, Rizk RA. Spectrophotometric studies on antioxidants-doped liposomes. J Am Sci 2011;7(7):363-369.
  • 3. Madawala SR, Andersson RE, Jastrebova JA, Almeida M, Dutta PC. Novel Conjugates of 1,3-Diacylglycerol and Lipoic Acid: Synthesis, DPPH Assay, and RP-LC-MS-APCI Analysis. J Lipids 2011:419809. doi: 10.1155/2011/419809.
  • 4. Niedowicz DM, Daleke DL. The role of oxidative stress in diabetic complications. Cell Biochem Biophys, 2005. 43(2):289-330.
  • 5. Rosen P, Nawroth P, King G, Moller W, Tritschler HJ, Packer L. The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCO-MCBN, the American Diabetes Association and the German Diabetes Society. Diabetes Metab Res Rev 2001;7(3):189-212. doi: 10.1002/dmrr.196.
  • 6. Kowluru RA, and Chan PS, Oxidative stress and diabetic retinopathy. Exp Diabetes Res 2007;43603. doi: 10.1155/2007/43603.
  • 7. Johansen JS, Harris AK, Rychly DJ, Ergul A. Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Cardiovasc Diabetol 2005;29;(4):5. doi: 10.1186/1475-2840-4-5.
  • 8. Sharafati-Chaleshtori R, Shirzad H, Rafieian-Kopaei M, Soltani A. Melatonin and human mitochondrial diseases. J Res Med Sci 2017;22:2. doi: 10.4103/1735-1995.199092.
  • 9. Acuna Castroviejo D, Lopez LC, Escames, López A, Garcia AJ, Reiter JR. Melatonin-mitochondria interplay in health and disease. Current topics in medicinal chemistry 2011;11(2):221-240.
  • 10. Anisimov VN., Effects of exogenous melatonin—a review. Toxicologic pathology, 2003. 31(6):589-603.
  • 11. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. Journal of biological chemistry 1951;193:265-275.
  • 12. Buege JA, Aust SD. Microsomal lipid peroxidation. Methods in enzymology 1978;52:302-310.
  • 13. Beutler E. Improved method for the determination of blood glutathione. J. lab. clin. Med 1963;61:882-888.
  • 14. Beers RF, Sizer IW. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol chem 1952;195(1):133-140.
  • 15. Gray SP, Jandeleit-Dahm K. The pathobiology of diabetic vascular complications—cardiovascular and kidney disease. Journal of Molecular Medicine 2014;92(5):441-452.
  • 16. Hamamcıoglu AC. Diyabette Oksidatif Stres ve Antioksidanların Rolü. Türkiye Diyabet ve Obezite Dergisi 2017;1(1):7-13.
  • 17. Elbe H, Vardi N, Esrefoglu M, Ates B, Yologlu S, Taskapan C. Amelioration of streptozotocin-induced diabetic nephropathy by melatonin, quercetin, and resveratrol in rats. Human & experimental toxicology 2015;34(1):100-113.
  • 18. Sekkin S, İpek ED, Boyacıoğlu M, et al. DNA protective and antioxidative effects of melatonin in streptozotocin-induced diabetic rats. Turkish Journal of Biology 2015;39(6):932-940.
  • 19. Bibak B, Khalili M, Rajaei Z, et al., Effects of melatonin on biochemical factors and food and water consumption in diabetic rats. Adv Biomed Res 2014;3:173. doi. 10.4103/2277-9175.139191.
  • 20. Andersson AK, Andler S, Melatonin protects against streptozotocin, but not interleukin‐1β‐induced damage of rodent pancreatic β‐cells. Journal of pineal research 2001;30(3):157-165.
  • 21. Avci E, Akaslan ZZ, Erten H, Coskun CS. Oxidative stress and cellular immunity in patients with recurrent aphthous ulcers. Brazilian Journal of Medical and Biological Research 2014;47(5):355-360.
  • 22. Öztürk AS, Ayekin İ, Özsoy ŞY, Öztğrk OH, Altuğ N, Yılmaz N. Effects of caffeic acid phenethyl ester on oxidative stress, hystopathology and some biochemical parameters in streptozotocin-induced diabetic rats/Streptozotocin ile indüklenen diyabetik sıçanlarda oksidatif stres, histopatolojik ve bazı biyokimyasal parametrelere kafeik asit fenetil esterin etkileri. Turkish Journal of Biochemistry 2015;40(2):149-156.
  • 23. Whiting PH, Kalansooriya A, Anura HI, Haddad F, Jennings PE. The relationship between chronic glycaemic control and oxidative stress in type 2 diabetes mellitus. British journal of biomedical science 2008;65(2):71-74.
  • 24. Jiménez-Osorio AS, Picazo A, González-Reyes S, Barrera-Oviedo D, Rodríguez-Arellano ME, Pedraza-Chaverri J. Nrf2 and redox status in prediabetic and diabetic patients. International journal of molecular sciences 2014;15(11):20290-20305.
  • 25. Annadurai T, Vasanthakumar A, Geraldine P, Thomas P. Variations in erythrocyte antioxidant levels and lipid peroxidation status and in serum lipid profile parameters in relation to blood haemoglobin A1c values in individuals with type 2 diabetes mellitus. Diabetes research and clinical practice 2014;105(1):58-69.
  • 26. Sajedianfard J, Behroozi Z, Nazifi S, Rajaian H. The effect of different oral doses of hydroalcoholic extract of silymarin on the blood oxidative stress indicators in streptozotocin induced diabetic rats. Int J Pept Res Ther 2013; 19:93–98.
  • 27. Zhang C, Lu X, Tan Y, et al. Diabetes-induced hepatic pathogenic damage, inflammation, oxidative stress, and insulin resistance was exacerbated in zinc deficient mouse model. PLoS One 2012;7(12):e49257.
  • 28. Petrović A, Bogojević D, Korać A, et al., Oxidative stress-dependent contribution of HMGB1 to the interplay between apoptosis and autophagy in diabetic rat liver. Journal of physiology and biochemistry 2017;73(4):511-521.
  • 29. Elbe H, Esrefoglu M, Vardi N, Taslıdere EÇ, Ozerol E, Tanbek K. Melatonin, quercetin and resveratrol attenuates oxidative hepatocellular injury in streptozotocin-induced diabetic rats. Human & experimental toxicology 2015;34(9):859-868.
  • 30. Allagui MS, Feriani A, Bouoni Z, Alimi H, Murat JC, El-Feki A. Protective effects of vitamins (C and E) and melatonin co-administration on hematological and hepatic functions and oxidative stress in alloxan-induced diabetic rats. Journal of physiology and biochemistry 2014;70(3):713-723.
  • 31. Yavuz O, Cam M, Bukan N, Guven AÇ, Silan F. Protective effect of melatonin on β-cell damage in streptozotocin-induced diabetes in rats. acta histochemica 2003;105(3):261-266.
  • 32. Şekeroğlu MR, Huyut Z, Çokluk E, Özbek H, Alp HH, The susceptibility to autoxidation of erythrocytes in diabetic mice: Effects of melatonin and pentoxifylline. Journal of biochemical and molecular toxicology 2017;31(12):e21976.

Antioxidant Activity of Melatoninin in Streptozotocin-İnduced Diabetic Rats; Blood and Liver Tissue

Year 2020, Volume: 10 Issue: 4, 608 - 614, 15.12.2020
https://doi.org/10.31832/smj.787622

Abstract

OBJECTIVE: In this study, it was aimed to investigate the antioxidant protective effect of melatonin supplementation against oxidative damage in blood and liver tissues of rats with experimental type 1 diabetes with Streptozotocin (STZ).
MATERIALS AND METHODS: Forty adult Spraque Dawley male rats; Group 1-Control group, Group 2-diabetes group, Group 3- melatonin supplement group and Group 4- diabetes and melatonin supplement group were divided into four groups. Diabetes was induced in rats by administering a single dose of 60 mg / kg STZ intraperitoneally. Melatonin supplementation was administered at a dose of 10 mg / kg / day subcutaneously for 6 weeks. Glutathione (GSH), catalase (CAT) and malondialdehyde (MDA) levels were measured spectrophotometrically in the liver and serum samples taken at the end of the experiment.
RESULTS: The results of the study showed that MDA levels increased in the serum and liver tissues of diabetic animals. It was observed that melatonin administration decreased MDA levels in both tissues, increased GSH and CAT levels or kept them stable by preventing it from falling (p <0.05).
CONCLUSION: The results of this study are consistent with the consensus that emphasizes and accepts that one of the main causes of complications of diabetes is oxidative stress. Our results show that melatonin has an ameliorating effect on increased oxidative stress in diabetes and melatonin can be used as a therapeutic agent.

Project Number

2018-08-06-001

References

  • KAYNAKLAR 1. Matough FA, Budin SB, Hamid ZA, Alwahaibi N, Mohamed J. The role of oxidative stress and antioxidants in diabetic complications. Sultan Qaboos University Medical Journal 2012;12(1):1-5.
  • 2. El Faramawy SM, Rizk RA. Spectrophotometric studies on antioxidants-doped liposomes. J Am Sci 2011;7(7):363-369.
  • 3. Madawala SR, Andersson RE, Jastrebova JA, Almeida M, Dutta PC. Novel Conjugates of 1,3-Diacylglycerol and Lipoic Acid: Synthesis, DPPH Assay, and RP-LC-MS-APCI Analysis. J Lipids 2011:419809. doi: 10.1155/2011/419809.
  • 4. Niedowicz DM, Daleke DL. The role of oxidative stress in diabetic complications. Cell Biochem Biophys, 2005. 43(2):289-330.
  • 5. Rosen P, Nawroth P, King G, Moller W, Tritschler HJ, Packer L. The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCO-MCBN, the American Diabetes Association and the German Diabetes Society. Diabetes Metab Res Rev 2001;7(3):189-212. doi: 10.1002/dmrr.196.
  • 6. Kowluru RA, and Chan PS, Oxidative stress and diabetic retinopathy. Exp Diabetes Res 2007;43603. doi: 10.1155/2007/43603.
  • 7. Johansen JS, Harris AK, Rychly DJ, Ergul A. Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Cardiovasc Diabetol 2005;29;(4):5. doi: 10.1186/1475-2840-4-5.
  • 8. Sharafati-Chaleshtori R, Shirzad H, Rafieian-Kopaei M, Soltani A. Melatonin and human mitochondrial diseases. J Res Med Sci 2017;22:2. doi: 10.4103/1735-1995.199092.
  • 9. Acuna Castroviejo D, Lopez LC, Escames, López A, Garcia AJ, Reiter JR. Melatonin-mitochondria interplay in health and disease. Current topics in medicinal chemistry 2011;11(2):221-240.
  • 10. Anisimov VN., Effects of exogenous melatonin—a review. Toxicologic pathology, 2003. 31(6):589-603.
  • 11. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. Journal of biological chemistry 1951;193:265-275.
  • 12. Buege JA, Aust SD. Microsomal lipid peroxidation. Methods in enzymology 1978;52:302-310.
  • 13. Beutler E. Improved method for the determination of blood glutathione. J. lab. clin. Med 1963;61:882-888.
  • 14. Beers RF, Sizer IW. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol chem 1952;195(1):133-140.
  • 15. Gray SP, Jandeleit-Dahm K. The pathobiology of diabetic vascular complications—cardiovascular and kidney disease. Journal of Molecular Medicine 2014;92(5):441-452.
  • 16. Hamamcıoglu AC. Diyabette Oksidatif Stres ve Antioksidanların Rolü. Türkiye Diyabet ve Obezite Dergisi 2017;1(1):7-13.
  • 17. Elbe H, Vardi N, Esrefoglu M, Ates B, Yologlu S, Taskapan C. Amelioration of streptozotocin-induced diabetic nephropathy by melatonin, quercetin, and resveratrol in rats. Human & experimental toxicology 2015;34(1):100-113.
  • 18. Sekkin S, İpek ED, Boyacıoğlu M, et al. DNA protective and antioxidative effects of melatonin in streptozotocin-induced diabetic rats. Turkish Journal of Biology 2015;39(6):932-940.
  • 19. Bibak B, Khalili M, Rajaei Z, et al., Effects of melatonin on biochemical factors and food and water consumption in diabetic rats. Adv Biomed Res 2014;3:173. doi. 10.4103/2277-9175.139191.
  • 20. Andersson AK, Andler S, Melatonin protects against streptozotocin, but not interleukin‐1β‐induced damage of rodent pancreatic β‐cells. Journal of pineal research 2001;30(3):157-165.
  • 21. Avci E, Akaslan ZZ, Erten H, Coskun CS. Oxidative stress and cellular immunity in patients with recurrent aphthous ulcers. Brazilian Journal of Medical and Biological Research 2014;47(5):355-360.
  • 22. Öztürk AS, Ayekin İ, Özsoy ŞY, Öztğrk OH, Altuğ N, Yılmaz N. Effects of caffeic acid phenethyl ester on oxidative stress, hystopathology and some biochemical parameters in streptozotocin-induced diabetic rats/Streptozotocin ile indüklenen diyabetik sıçanlarda oksidatif stres, histopatolojik ve bazı biyokimyasal parametrelere kafeik asit fenetil esterin etkileri. Turkish Journal of Biochemistry 2015;40(2):149-156.
  • 23. Whiting PH, Kalansooriya A, Anura HI, Haddad F, Jennings PE. The relationship between chronic glycaemic control and oxidative stress in type 2 diabetes mellitus. British journal of biomedical science 2008;65(2):71-74.
  • 24. Jiménez-Osorio AS, Picazo A, González-Reyes S, Barrera-Oviedo D, Rodríguez-Arellano ME, Pedraza-Chaverri J. Nrf2 and redox status in prediabetic and diabetic patients. International journal of molecular sciences 2014;15(11):20290-20305.
  • 25. Annadurai T, Vasanthakumar A, Geraldine P, Thomas P. Variations in erythrocyte antioxidant levels and lipid peroxidation status and in serum lipid profile parameters in relation to blood haemoglobin A1c values in individuals with type 2 diabetes mellitus. Diabetes research and clinical practice 2014;105(1):58-69.
  • 26. Sajedianfard J, Behroozi Z, Nazifi S, Rajaian H. The effect of different oral doses of hydroalcoholic extract of silymarin on the blood oxidative stress indicators in streptozotocin induced diabetic rats. Int J Pept Res Ther 2013; 19:93–98.
  • 27. Zhang C, Lu X, Tan Y, et al. Diabetes-induced hepatic pathogenic damage, inflammation, oxidative stress, and insulin resistance was exacerbated in zinc deficient mouse model. PLoS One 2012;7(12):e49257.
  • 28. Petrović A, Bogojević D, Korać A, et al., Oxidative stress-dependent contribution of HMGB1 to the interplay between apoptosis and autophagy in diabetic rat liver. Journal of physiology and biochemistry 2017;73(4):511-521.
  • 29. Elbe H, Esrefoglu M, Vardi N, Taslıdere EÇ, Ozerol E, Tanbek K. Melatonin, quercetin and resveratrol attenuates oxidative hepatocellular injury in streptozotocin-induced diabetic rats. Human & experimental toxicology 2015;34(9):859-868.
  • 30. Allagui MS, Feriani A, Bouoni Z, Alimi H, Murat JC, El-Feki A. Protective effects of vitamins (C and E) and melatonin co-administration on hematological and hepatic functions and oxidative stress in alloxan-induced diabetic rats. Journal of physiology and biochemistry 2014;70(3):713-723.
  • 31. Yavuz O, Cam M, Bukan N, Guven AÇ, Silan F. Protective effect of melatonin on β-cell damage in streptozotocin-induced diabetes in rats. acta histochemica 2003;105(3):261-266.
  • 32. Şekeroğlu MR, Huyut Z, Çokluk E, Özbek H, Alp HH, The susceptibility to autoxidation of erythrocytes in diabetic mice: Effects of melatonin and pentoxifylline. Journal of biochemical and molecular toxicology 2017;31(12):e21976.
There are 32 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Articles
Authors

Songül Doğanay 0000-0002-1730-1331

Şeyma Trabzon 0000-0001-9030-7804

Nurten Bahtiyar 0000-0003-2420-8415

Derya Güzel 0000-0002-7618-5043

Ayla Eren Özdemir 0000-0002-0555-7049

Arzu Şahin 0000-0002-8789-4582

Project Number 2018-08-06-001
Publication Date December 15, 2020
Submission Date August 29, 2020
Published in Issue Year 2020 Volume: 10 Issue: 4

Cite

AMA Doğanay S, Trabzon Ş, Bahtiyar N, Güzel D, Eren Özdemir A, Şahin A. Streptozotosin ile İndüklenmiş Diyabetik Sıçanlarda Melatoninin Antioksidan Aktivitesi; Kan ve Karaciğer Dokusunda. Sakarya Tıp Dergisi. December 2020;10(4):608-614. doi:10.31832/smj.787622

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