Skip to main content
Log in

Effects of Melatonin on Streptozotocin-Induced Retina Neuronal Apoptosis in High Blood Glucose Rat

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

One of the main pathological symptoms of early diabetic retinal neuropathy is retina neuronal apoptosis. In the present work we investigated the effects of indoleamine hormone melatonin, a powerful free radical scavenger, on streptozotocin-induced retina neuronal cell apoptosis in high blood glucose rat. After melatonin treatment (10 mg/kg/day), tunel detection was used to monitor the apoptosis rate of neurons in the retinal ganglion cell layer; reversed quantitative PCR was used to measure the mRNA expression of retinal caspase-3, Mn superoxidase dismutase (SOD) and Cu–Zn SOD; and the activities of total SOD (T-SOD) and sub-type SOD was detected using xanthine oxidase enzymatic detection. Our data showed that melatonin treatment leads to a decrease of retinal cell apoptosis and the apoptotic index was (1.67 ± 0.54) % and (7.73 ± 0.95) % at 8 and 12 weeks after treatment. The relative quantitative (RQ) value for caspase-3 mRNA expression was (6.996 ± 1.192) and (7.267 ± 1.178) in melatonin group, which are much lower than the values of diabetic group (12.566 ± 2.272 and (14.297 ± 2.110) at 8 and 12 weeks, respectively) under the same condition. mRNA expression of Mn SOD and Cu–Zn SOD as well as their activities all decreased in the diabetic group compared with the control group. While melatonin treatment induced the expression of Mn SOD mRNA and a continual increase of Mn SOD activity as well as the activity and mRNA expression of Cu–Zn SOD at 12 weeks. Therefore, our results demonstrate that melatonin treatment prevented the decrease in mRNA expression of SOD and the increase in caspase-3 mRNA expression induced by diabetes thus exerts a beneficial effect on retina neuronal apoptosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54(6):1615–1625

    Article  PubMed  CAS  Google Scholar 

  2. Rolo AP, Palmeira CM (2006) Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress. Toxicol Appl Pharmacol 212(2):167–178. doi:10.1016/j.taap.2006.01.003

    Article  PubMed  CAS  Google Scholar 

  3. Russell JW, Golovoy D, Vincent AM, Mahendru P, Olzmann JA, Mentzer A, Feldman EL (2002) High glucose-induced oxidative stress and mitochondrial dysfunction in neurons. FASEB J 16(13):1738–1748. doi:10.1096/fj.01-1027com

    Article  PubMed  CAS  Google Scholar 

  4. Schmeichel AM, Schmelzer JD, Low PA (2003) Oxidative injury and apoptosis of dorsal root ganglion neurons in chronic experimental diabetic neuropathy. Diabetes 52(1):165–171

    Article  PubMed  CAS  Google Scholar 

  5. Anuradha CD, Kanno S, Hirano S (2001) Oxidative damage to mitochondria is a preliminary step to caspase-3 activation in fluoride-induced apoptosis in HL-60 cells. Free Radical Bio Med 31(3):367–373

    Article  CAS  Google Scholar 

  6. Phaneuf S, Leeuwenburgh C (2002) Cytochrome c release from mitochondria in the aging heart: a possible mechanism for apoptosis with age. Am J Physiol-Reg I 282(2):R423–R430

    CAS  Google Scholar 

  7. Haskins K, Bradley B, Powers K, Fadok V, Flores S, Ling X, Pugazhenthi S, Reusch J, Kench J (2003) Oxidative stress in type 1 diabetes. Ann N Y Acad Sci 1005:43–54

    Article  PubMed  CAS  Google Scholar 

  8. Stehle JH, Saade A, Rawashdeh O, Ackermann K, Jilg A, Sebesteny T, Maronde E (2011) A survey of molecular details in the human pineal gland in the light of phylogeny, structure, function and chronobiological diseases. J Pineal Res 51(1):17–43. doi:10.1111/j.1600-079X.2011.00856.x

    Article  PubMed  CAS  Google Scholar 

  9. Reiter RJ, Tan DX, Burkhardt S (2002) Reactive oxygen and nitrogen species and cellular and organismal decline: amelioration with melatonin. Mech Ageing Dev 123(8):1007–1019

    Article  PubMed  CAS  Google Scholar 

  10. Korkmaz A, Reiter RJ, Topal T, Manchester LC, Oter S, Tan DX (2009) Melatonin: an established antioxidant worthy of use in clinical trials. Mol Med 15(1–2):43–50. doi:10.2119/molmed.2008.00117

    PubMed  CAS  Google Scholar 

  11. Bonnefont-Rousselot D, Collin F, Jore D, Gardes-Albert M (2011) Reaction mechanism of melatonin oxidation by reactive oxygen species in vitro. J Pineal Res 50(3):328–335. doi:10.1111/j.1600-079X.2010.00847.x

    Article  PubMed  CAS  Google Scholar 

  12. Galano A, Tan DX, Reiter RJ (2011) Melatonin as a natural ally against oxidative stress: a physicochemical examination. J Pineal Res 51(1):1–16. doi:10.1111/j.1600-079X.2011.00916.x

    Article  PubMed  CAS  Google Scholar 

  13. Chang HM, Huang YL, Lan CT, Wu UI, Hu ME, Youn SC (2008) Melatonin preserves superoxide dismutase activity in hypoglossal motoneurons of adult rats following peripheral nerve injury. J Pineal Res 44(2):172–180. doi:10.1111/j.1600-079X.2007.00505.x

    Article  PubMed  CAS  Google Scholar 

  14. Zwirska-Korczala K, Jochem J, Adamczyk-Sowa M, Sowa P, Polaniak R, Birkner E, Latocha M, Pilc K, Suchanek R (2005) Influence of melatonin on cell proliferation, antioxidative enzyme activities and lipid peroxidation in 3T3-L1 preadipocytes–an in vitro study. J Physiol Pharmacol 56(Suppl 6):91–99

    PubMed  Google Scholar 

  15. Klepac N, Rudes Z, Klepac R (2006) Effects of melatonin on plasma oxidative stress in rats with streptozotocin induced diabetes. Biomed Pharmacother 60(1):32–35. doi:10.1016/j.biopha.2005.08.005

    Article  PubMed  CAS  Google Scholar 

  16. Kim SH, Lee SM (2008) Cytoprotective effects of melatonin against necrosis and apoptosis induced by ischemia/reperfusion injury in rat liver. J Pineal Res 44(2):165–171. doi:10.1111/j.1600-079X.2007.00504.x

    Article  PubMed  CAS  Google Scholar 

  17. Baydas G, Tuzcu M, Yasar A, Baydas B (2004) Early changes in glial reactivity and lipid peroxidation in diabetic rat retina: effects of melatonin. Acta Diabetol 41(3):123–128

    Article  PubMed  CAS  Google Scholar 

  18. Kowluru RA, Atasi L, Ho YS (2006) Role of mitochondrial superoxide dismutase in the development of diabetic retinopathy. Invest Ophthalmol Vis Sci 47(4):1594–1599. doi:10.1167/iovs.05-1276

    Article  PubMed  Google Scholar 

  19. Colombrita C, Calabrese V, Stella AM, Mattei F, Alkon DL, Scapagnini G (2003) Regional rat brain distribution of heme oxygenase-1 and manganese superoxide dismutase mRNA: relevance of redox homeostasis in the aging processes. Exp Biol Med (Maywood) 228(5):517–524

    CAS  Google Scholar 

  20. Wu J, Gorman A, Zhou X, Sandra C, Chen E (2002) Involvement of caspase-3 in photoreceptor cell apoptosis induced by in vivo blue light exposure. Invest Ophthalmol Vis Sci 43(10):3349–3354

    PubMed  Google Scholar 

  21. Limaye PV, Raghuram N, Sivakami S (2003) Oxidative stress and gene expression of antioxidant enzymes in the renal cortex of streptozotocin-induced diabetic rats. Mol Cell Biochem 243(1–2):147–152

    Article  PubMed  CAS  Google Scholar 

  22. Kim J, Yokoyama K, Araki S (2000) The effects of Ginkgo biloba extract (GBe) on axonal transport microvasculature and morphology of sciatic nerve in streptozotocin-induced diabetic rats. Environ Health Prev Med 5(2):53–59. doi:10.1007/BF02932004

    Article  PubMed  CAS  Google Scholar 

  23. Sudnikovich EJ, Maksirachik YZ, Zabrodskaya SV, Kubyshin VL, Lapshina EA, Bryszewska M, Reiter RJ, Zavodnik IB (2007) Melatonin attenuates metabolic disorders due to streptozotocin-induced diabetes in rats. Eur J Pharmacol 569(3):180–187. doi:10.1016/j.ejphar.2007.05.018

    Article  PubMed  CAS  Google Scholar 

  24. Esparza JL, Gomez M, Rosa Nogues M, Paternain JL, Mallol J, Domingo JL (2005) Melatonin reduces oxidative stress and increases gene expression in the cerebral cortex and cerebellum of aluminum-exposed rats. J Pineal Res 39(2):129–136. doi:10.1111/j.1600-079X.2005.00225.x

    Article  PubMed  CAS  Google Scholar 

  25. Kanter M, Uysal H, Karaca T, Sagmanligil HO (2006) Depression of glucose levels and partial restoration of pancreatic beta-cell damage by melatonin in streptozotocin-induced diabetic rats. Arch Toxicol 80(6):362–369. doi:10.1007/s00204-005-0055-z

    Article  PubMed  CAS  Google Scholar 

  26. Sharma S, Haldar C (2009) Comparative effect of melatonin and vitamin E on phenylhydrazine-induced toxicity in the Spleen of Funambulus pennanti. Environ Toxicol 24(1):1–9. doi:10.1002/Tox.20383

    Article  PubMed  CAS  Google Scholar 

  27. Vural H, Sabuncu T, Arslan SO, Aksoy N (2001) Melatonin inhibits lipid peroxidation and stimulates the antioxidant status of diabetic rats. J Pineal Res 31(3):193–198

    Article  PubMed  CAS  Google Scholar 

  28. Marshall KA, Reiter RJ, Poeggeler B, Aruoma OI, Halliwell B (1996) Evaluation of the antioxidant activity of melatonin in vitro. Free Radic Biol Med 21(3):307–315

    Article  PubMed  CAS  Google Scholar 

  29. Allegra M, Reiter RJ, Tan DX, Gentile C, Tesoriere L, Livrea MA (2003) The chemistry of melatonin’s interaction with reactive species. J Pineal Res 34(1):1–10

    Article  PubMed  CAS  Google Scholar 

  30. Rodriguez C, Mayo JC, Sainz RM, Antolin I, Herrera F, Martin V, Reiter RJ (2004) Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res 36(1):1–9

    Article  PubMed  CAS  Google Scholar 

  31. Batcioglu K, Karagozler AA, Genc M, Celik S (2002) Comparison of the chemopreventive potentials of melatonin and vitamin E plus selenium on 7,12-dimethylbenz[a]anthracene-induced inhibition of mouse liver antioxidant enzymes. Eur J Cancer Prev 11(1):57–61

    Article  PubMed  CAS  Google Scholar 

  32. Aktoz T, Aydogdu N, Alagol B, Yalcin O, Huseyinova G, Atakan IH (2007) The protective effects of melatonin and vitamin E against renal ischemia-reperfusion injury in rats. Ren Fail 29(5):535–542. doi:10.1080/08860220701391738

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maonian Zhang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, X., Zhang, M. & Tang, W. Effects of Melatonin on Streptozotocin-Induced Retina Neuronal Apoptosis in High Blood Glucose Rat. Neurochem Res 38, 669–676 (2013). https://doi.org/10.1007/s11064-012-0966-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-012-0966-z

Keywords

Navigation