Efficacy of melatonin in restoring the antioxidant status in the lens of diabetic rats induced by streptozotocin

  • Marjan Khorsand
  • Masoumeh AkmaliEmail author
  • Morteza Akhzari
Research article



Melatonin is a well-known free radical scavenger. The present study aimed to investigate the effects of melatonin treatment on the antioxidant status in the lenticular tissue of streptozotocin (STZ)-induced diabetic rats.


Thirty-four male rats were randomly divided into four groups as follows: healthy control rats (group 1, n = 10); diabetic control rats (group 2, n = 10); melatonin-treated (5 mg/kg·day) diabetic rats (group 3, n = 10) and melatonin-treated (5 mg/kg·day) healthy rats (group 4, n = 4). Diabetes was induced by injection of streptozotocin (50 mg/kg, ip). Following 8-weeks of melatonin treatment, all rats were killed and the blood plasma and their lenses were stored at −70 °C for antioxidant enzyme activities assay and biochemical determination.


The plasma glucose and lens malondialdehyde (MDA) increased significantly in the rats of group 2 as compared to the group 1. Also, a significant decrease in the levels of catalase (CAT) and glutathione reductase (GR) activities in the lenses and plasma reduced glutathione (GSH) was found. However, the levels of lenticular MDA (not significant) and the plasma glucose significantly decreased in the rats of group 3 compared to the group 2. Besides, the levels of CAT, GR in the rats lens and plasma GSH increased significantly.


Diabetes mellitus induced hyperglycemia and oxidative stress, whereas melatonin decreased the blood glucose levels and lipid peroxidation and increased the activities of antioxidant enzymes in diabetic rat lenses.


Antioxidant enzymes Diabetes Melatonin Oxidative stress Streptozotocin 



Reactive oxygen species




β-Nicotinamide adenine dinucleotide phosphate-reduced form


2-thiobarbituric acid


1, 1, 3, 3-tetra ethoxy propane


Reduced glutathione


5, 5′-dithiobis-(2-nitrobenzoic acid)


Oxidized glutathione






Glutathione reductase


Reduced nicotinamide adenine dinucleotide phosphate




Reduced glutathione


Superoxide dismutase


Glutathione peroxidase


Reactive nitrogen species


Ethylenediaminetetraacetic acid


Bovine serum albumin, Non-insulin-dependent diabetes mellitus (NIDDM)



The authors thank from the biochemistry department of Shiraz University of Medical Sciences for technical assistance in this work.

Authors’ contributions

Masoumeh Akmali contributed to the design the study, and drafted the manuscript, Masoumeh Akmali, Marjan Khorsand and Morteza Akhzari conducted the analysis, wrote and revised manuscript, Marjan Khorsand performed the biochemical analysis and animal treatment.


The Shahid Sadoughi University of Medical Sciences (Yazd, Iran) and Shiraz University of Medical Sciences (Shiraz, Iran) funded this study, which is derived from the student thesis of Marjan Khorsand by grant number 1083.

Compliance with ethical standards

Ethics approval and consent to participate

All experiments in this study performed according to the guidelines of “Animal Care Ethics Committee” of Shiraz University of Medical Sciences, Shiraz, Iran (IR.SUMS.REC).

Conflict of interest

There is no financial or personal conflict of interest.


  1. 1.
    De Oliveira AC, Andreotti S, Farias Tda S, Torres-Leal FL, de Proença AR, Campaña AB, et al. Metabolic disorders and adipose tissue insulin responsiveness in neonatally STZ-induced diabetic rats are improved by long-term melatonin treatment. Endocrinology. 2012;153(5):2178–88. Scholar
  2. 2.
    Andrew W, Siu MM, Sanchez-Hidalgo M, Tan DX, Reiter RJ. Protective effects of melatonin in experimental free radical-related ocular diseases. J Pineal Res. 2006;40:101–9. Scholar
  3. 3.
    Tuzcu M, Baydas G. Effect of melatonin and vitamin E on diabetes-induced learning and memory impairment in rats. Eur J Pharmacol. 2006;537:106–10. Scholar
  4. 4.
    Vural H, Sabuncu T, Arslan SO, Aksoy N. Melatonin inhibits lipid peroxidation and stimulates the antioxidant status of diabetic rats. J Pineal Res. 2001;31:193–8.CrossRefGoogle Scholar
  5. 5.
    Tarek A, Elkenawy A, Elbasuony M, Abskharon A. Antioxidant activities of cinnamon extract on diabetic rats. Tanta Med Sci J. 2010;5(1):42–9.Google Scholar
  6. 6.
    El-Bahr SM. Curcumin regulates gene expression of insulin like growth factor, B-cell CLL/lymphoma 2 and antioxidant enzymes in streptozotocin induced diabetic rats. BMC Complement Altern Med. 2013;13:368. Scholar
  7. 7.
    Klepac N, Rudes Z, Klepac R. Effects of melatonin on plasma oxidative stress in rats with streptozotocin induced diabetes. Biomed Pharmacother. 2006;60(1):32–5. Scholar
  8. 8.
    Karslioglu I, Ertekin MV, Taysi S, Koçer I, Sezen O, Gepdiremen A, et al. Radioprotective effects of melatonin on radiation-induced cataract. J Radiat Res. 2005;46:277–82.CrossRefGoogle Scholar
  9. 9.
    Kyselova Z, Stefek M, Bauer V. Pharmacological prevention of diabetic cataract. J Diabetes Complicat. 2004;18:129–40.CrossRefGoogle Scholar
  10. 10.
    Zhang J, Yan H, Lou MF. Does oxidative stress play any role in diabetic cataract formation? Re-evaluation using a thioltransferase gene knockout mouse model. Exp Eye Res. 2017;161:36–42.CrossRefGoogle Scholar
  11. 11.
    Hegde KR, Varma SD. Combination of glycemic and oxidative stress in lens: implications in augmentation of cataract formation in diabetes. Free Radic Res. 2005;39(5):513–7.CrossRefGoogle Scholar
  12. 12.
    Gürpınar T, Ekerbiçer N, Uysal N, Barut T, Tarakçı F, Tuglu MI. The effects of the melatonin treatment on the oxidative stress and apoptosis in diabetic eye and brain. Sci World J. 2012. Scholar
  13. 13.
    Agarkov AA, Popova TN, Verevkin AN, Matasova LV. Activity of the glutathione antioxidant system and NADPH-generating enzymes in blood serum of rats with type 2 diabetes mellitus after administration of melatonin-correcting drugs. Bull Exp Biol Med. 2014;157(2):198–201. Scholar
  14. 14.
    Shirazi A, Haddadi GH, Asadi-Amoli F, Sakhaee S, Ghazi-Khansari M, Avand A. Radioprotective effect of melatonin in reducing oxidative stress in rat lenses. Cell J (Yakhteh). 2011;13(2):79–82.Google Scholar
  15. 15.
    Xiaoyan L, Maonian Z, Weiqiang T. Effects of melatonin on Streptozotocin-induced retina neuronal apoptosis in high blood glucose rat. Neurochem Res. 2013;38:669–76. Scholar
  16. 16.
    Abdel-Wahab MH, Abd-Allah ARA. Possible protective effect of melatonin and/or desferrioxamine against streptozotocin-induced hyperglycaemia in mice. Pharmacol Res. 2001;41(5):533–7. Scholar
  17. 17.
    Kocer I, Taysi S, Ertekin MV, Karslioglu I, Gepdiremen A, Sezen O, et al. The effect of L-carnitine in the prevention of ionizing radiation-induced cataracts: a rat model. Graefes Arch Clin Exp Ophthalmol. 2007;245:588–94. Scholar
  18. 18.
    Massey V, Charles H, Williams JR. On the reaction mechanism of yeast glutathione reductase. J Biochem. 1965;240:4470–80.Google Scholar
  19. 19.
    Zal F, Mostafavipour Z, Vessal M. Comparison of vitamin E and/or quercetin in attenuating chronic cyclosporine induced nephrotoxicity in male rats. J Clin Exp Pharmacol Physiol. 2007;34:720–4. Scholar
  20. 20.
    Paulo SM, Barros AC. Antioxidant profile of cataractous English cocker spaniels. Vet Ophthalmol. 1999;2:83–6.CrossRefGoogle Scholar
  21. 21.
    Tietze F. Enzymic method for quantitative determination of Nanogram amount of total and oxidative glutathione. Anal Biochem. 1969;27:502–22.CrossRefGoogle Scholar
  22. 22.
    Reinhold JG. Total protein, albumin. And globulin.Stand methods. Clin Chem. 1952;1:88–97.Google Scholar
  23. 23.
    Barham D, Trinder P. An improved color reagent for the determination of blood glucose by the oxidase system. Analyst. 1972;97:142–5.CrossRefGoogle Scholar
  24. 24.
    Suryanarayana P, Saraswat M, Petrash JM, Reddy GB. Emblica officinalis and its enriched tannoids delay streptozotocin-induced diabetic cataract in rats. Mol Vis. 2007;13:1291–7.PubMedGoogle Scholar
  25. 25.
    Thiraphatthanavong P, Wattanathorn J, Muchimapura S, Wipawee TM, Wannanon P, Terdthai TU et al. Preventive effect of Zea mays L. (purple waxy corn) on experimental diabetic cataract. BiomedResInt; 2014:1-8. doi: Scholar
  26. 26.
    Armagan A, Uz E, Yilmaz HR, Soyupek S, Oksay T, Ozcelik N. Effects of melatonin on lipid peroxidation and antioxidant enzymes in streptozotocin-induced diabetic rat testis. Asian J Androl. 2006;8(5):595–600. Scholar
  27. 27.
    Ozlem Y, Meryem C, Neslihan B, Aysel G, Fatma S. Protective effect of melatonin on ß-cell damage in streptozotocin-induced diabetes in rats. Acta Histochem. 2003;105(3):261–6.CrossRefGoogle Scholar
  28. 28.
    Anwar M, Meki AMA. Oxidative stress in streptozotocin- induced diabetic rats: effects of garlic oil and melatonin. Comp Biochem Physiol A Mol Integr Physiol. 2003;135:539–47.CrossRefGoogle Scholar
  29. 29.
    Mohamed SA, Anouer F, Zouhour B, Hichem A, Jean C, Abdelfattah E. Protective effects of vitamins (C and E) and melatonin co-administration on hematological and hepatic functions and oxidative stress in alloxan-induced diabetic rats. J Physiol Biochem. 2014;70:713–23. Scholar
  30. 30.
    Akmali M, Ahmadi R, Vessal M. Pre- and post-treatment of streptozocin administered rats with melatonin: effects on some hepatic enzymes of carbohydrate metabolism. Arch Iran Med. 2010;13:105–10.PubMedGoogle Scholar
  31. 31.
    Khorsand M, Akmali M, Sharzad S, Beheshtitabar M. Melatonin reduces cataract formation and aldose reductase activity in Streptozotocin-induced diabetic rat lenses. Iran J Med Sci 2016.Google Scholar
  32. 32.
    Sudnikovich EJ, Maksimchik YZ, Zabrodskaya SV, Kubyshin VL, Lapshina EA, Bryszewska M, et al. Melatonin attenuates metabolic disorders due to streptozotocin-induced diabetes in rats. Eur J Pharmacol. 2007;569(3):180–7. Scholar
  33. 33.
    Negi G, Kumar A, Kaundal RK, Gulati A, Sharma SS. Functional and biochemical evidence indicating beneficial effect of melatonin and nicotinamide alone and in combination in experimental diabetic neuropathy. Neuropharmacology. 2010;58:585–92. Scholar
  34. 34.
    Sekkin S, Ipek E, Boyacioğlu M, Kum C, Karademir U, Yalinkilinç H, et al. DNA protective and antioxidative effects of melatonin in streptozotocin-induced diabetic rats. Turk J Biol. 2015;39:932–40.CrossRefGoogle Scholar
  35. 35.
    Zhang S, Chai FY, Yan H, Guo Y, Harding JJ. Effects of N-acetylcysteine and glutathione ethyl ester drops on streptozotocin induced diabetic cataract in rats. Mol Vis. 2008;14:862–70.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Koziróg M, Poliwczak AR, Duchnowicz P, Koter-Michalak M. Melatonin treatment improves blood pressure, lipid profile, and parameters of oxidative stress in patients with metabolic syndrome. J Pineal Res. 2011;50:261–6.CrossRefGoogle Scholar
  37. 37.
    Kedziora-Kornatowska K, Szewczyk-Golec K, Kozakiewicz M, Pawluk H, Czuczejko J, Kornatowski T, et al. Melatonin improves oxidative stress parameters measured in the blood of elderly type 2 diabetic patients. J Pineal Res. 2009;46:333–7.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Marjan Khorsand
    • 1
    • 2
  • Masoumeh Akmali
    • 2
    Email author
  • Morteza Akhzari
    • 2
  1. 1.Department of Biochemistry and Molecular BiologyShahid Sadoughi University of Medical SciencesYazdIran
  2. 2.Department of BiochemistryShiraz University of Medical Sciences, Medical SchoolShirazIran

Personalised recommendations