Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Ellagic acid attenuates oxidative stress on brain and sciatic nerve and improves histopathology of brain in streptozotocin-induced diabetic rats

  • 863 Accesses

  • 66 Citations

Abstract

The aim of this study was to investigate the possible effects of ellagic acid in brain and sciatic nerve tissues of diabetic rats. Also, the impact of ellagic acid on catalase and paraoxonase (PON-1) activities, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), malondialdehyde (MDA) and nitric oxide (NO) were examined. The rats were randomly divided into four groups, with eight rats each: Normal controls (not diabetic), only ellagic acid treated (ellagic acid controls, not diabetic), Diabetic controls (streptozotocin, diabetic), ellagic acid-treated diabetic (streptozotocin + ellagic acid). After a 4 week experiment, rats were sacrificed, and biomarkers for oxidative stress in the brain and sciatic nerve tissues of the rats were measured. There was significant depletion in the PON-1, catalase, and TAS levels in the brain and sciatic nerve tissues compared to the control groups (for both parameters, p < 0.05). The values of catalase, PON-1 and TAS reversed back to normal levels in ellagic acid-treated diabetic rats compared to untreated diabetic rats (for both parameters, p < 0.05). The levels of MDA, TOS, NO and, OSI in the brain and sciatic nerve tissues were higher in untreated diabetic rats compared to control group (for both parameters p < 0.05). However, MDA, TOS, OSI, and NO levels were found to be significantly reduced in the ellagic acid-treated diabetic group compared to the untreated diabetic group in these tissues (for both parameters, p < 0.05). In conclusion, the results of the present study suggested that ellagic acid exhibits neuroprotective effects against oxidative damage in diabetic rats.

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

Fig. 1

References

  1. 1.

    Manschot SM, Biessels GJ, Rutten GE, Kessels RP, Gispen WH, Kappelle LJ, Utrecht Diabetic Encephalopathy Study Group (2008) Peripheral and central neurologic complications in type 2 diabetes mellitus: no association in individual patients. J Neurol Sci 264:157–162

  2. 2.

    Ozkul A, Ayhan M, Yenisey C, Akyol A, Guney E, Ergin FA (2010) The role of oxidative stress and endothelial injury in diabetic neuropathy and neuropathic pain. Neuro Endocrinol Lett 31:261–264

  3. 3.

    Osawa T, Kato Y (2005) Protective role of antioxidative food factors in oxidative stress caused by hyperglycemia. Ann N Y Acad Sci 1043:440–451

  4. 4.

    Gumieniczek A (2005) Effects of pioglitazone on hyperglycemia-induced alterations in antioxidative system in tissues of alloxan-treated diabetic animals. Exp Toxicol Pathol 56:321–326

  5. 5.

    Chandrasekharan B, Anitha M, Blatt R, Shahnavaz N, Kooby D, Staley C, Mwangi S, Jones DP, Sitaraman SV, Srinivasan S (2011) Colonic motor dysfunction in human diabetes is associated with enteric neuronal loss and increased oxidative stress. Neurogastroenterol Motil 23:131–138

  6. 6.

    Okouchi M, Okayama N, Aw TY (2009) Preservation of cellular glutathione status and mitochondrial membrane potential by N-acetylcysteine and insulin sensitizers prevent carbonyl stress-induced human brain endothelial cell apoptosis. Curr Neurovasc Res 6:267–278

  7. 7.

    Bakkalbasi E, Mentes O, Artik N (2009) Food ellagitannins-occurrence, effects of processing and storage. Crit Rev Food Sci Nutr 49:283–298

  8. 8.

    Seeram NP, Adams LS, Henning SM, Niu Y, Zhang Y, Nair MG, Heber D (2005) In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J Nutr Biochem 16:360–367

  9. 9.

    Ou HC, Lee WJ, Lee SD, Huang CY, Chiu TH, Tsai KL, Hsu WC, Sheu WH (2010) Ellagic acid protects endothelial cells from oxidized low-density lipoprotein-induced apoptosis by modulating the PI3 K/Akt/eNOS pathway. Toxicol Appl Pharmacol 248:134–143

  10. 10.

    Ueda H, Kawanishi K, Moriyasu M (2004) Effects of ellagic acid and 2-(2, 3, 6-trihydroxy-4-carboxyphenyl) ellagic acid on sorbitol accumulation in vitro and in vivo. Biol Pharm Bull 27:1584–1587

  11. 11.

    Shanmugam KR, Mallikarjuna K, Kesireddy N, Sathyavelu Reddy K (2011) Neuroprotective effect of ginger on anti-oxidant enzymes in streptozotocin-induced diabetic rats. Food Chem Toxicol 49:893–897

  12. 12.

    Alp H, Aytekin I, Atakisi O, Hatipoglu NK, Basarali K, Ogun M, Buyukbas S, Altintas L, Ekici H, Alp A (2011) The effects of caffeic acid phenethyl ester and ellagic acid on the levels of malondialdehyde, reduced glutathione and nitric oxide in the lung, liver and kidney tissues in acute diazinon toxicity in rats. J Anim Vet Adv 10:1488–1494

  13. 13.

    Lowry OH, Rosebrough NJ, Farr AL, Randal RJ (1951) Protein measurement with the Folin phenol reagent. J Biochem Chem 19:265–275

  14. 14.

    Ohkawa H, Ohishi N, Tagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

  15. 15.

    Cortas NK, Wakid NW (1990) Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. Clin Chem 36:1440–1443

  16. 16.

    Eckerson HW, Wyte CM, La Du BN (1983) The human serum paraoxonase/arylesterase polymorphism. Am J Hum Genet 35:1126–1138

  17. 17.

    Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

  18. 18.

    Erel O (2004) A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem 37:112–119

  19. 19.

    Erel O (2005) A new automated colorimetric method for measuring total oxidant status. Clin Biochem 38:1103–1111

  20. 20.

    Ozturk E, Balat O, Acılmıs YG, Ozcan C, Pence S, Erel O (2011) Measurement of the placental total antioxidant status in preeclamptic women using a novel automated method. J Obstet Gynaecol Res 37:337–342

  21. 21.

    Aslan M, Sabuncu T, Kocyigit A, Celik H, Selek S (2007) Relationship between total oxidant status and severity of diabetic nephropathy in type 2 diabetic patients. Nutr Metab Cardiovasc Dis 17:734–740

  22. 22.

    Yilmaz HR, Uz E, Yucel N, Altuntas I, Ozcelik N (2004) Protective effect of caffeic acid phenethyl ester (CAPE) on lipid peroxidation and antioxidant enzymes in diabetic rat liver. J Biochem Mol Toxicol 18:234–238

  23. 23.

    Kumar A, Kaundal RK, Iyer S, Sharm SS (2007) Effects of resveratrol on nerve functions, oxidative stress and DNA fragmentation in experimental diabetic neuropathy. Life Sci 80:1236–1244

  24. 24.

    Umesalma S, Sudhandiran G (2010) Differential inhibitory effects of the polyphenol ellagic acid on inflammatory mediators NF-kappaB, iNOS, COX-2, TNF-alpha, and IL-6 in 1, 2-dimethylhydrazine-induced rat colon carcinogenesis. Basic Clin Pharmacol Toxicol 107:650–655

  25. 25.

    Maes M, Galecki P, Chang YS, Berk M (2011) A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro) degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiat 35:676–692

  26. 26.

    Chao PC, Hsu CC, Yin MC (2009) Anti-inflammatory and anti-coagulatory activities of caffeic acid and ellagic acid in cardiac tissue of diabetic mice. Nutr Metab (Lond). doi:10.1186/1743-7075-6-33

  27. 27.

    Chao CY, Mong MC, Chan KC, Yin MC (2010) Anti-glycative and anti-inflammatory effects of caffeic acid and ellagic acid in kidney of diabetic mice. Mol Nutr Food Res 54:388–395

  28. 28.

    Kawanishi K, Ueda H, Moriyasu M (2003) Aldose reductase inhibitors from the nature. Curr Med Chem 10:1353–1374

  29. 29.

    Nambu H, Kubo E, Takamura Y, Tsuzuki S, Tamura M, Akagi Y (2008) Attenuation of aldose reductase gene suppresses high-glucose-induced apoptosis and oxidative stress in rat lens epithelial cells. Diabetes Res Clin Pract 82:18–24

  30. 30.

    Inoue M, Suehiro T, Nakamura T, Ikeda Y, Kumon Y, Hashimoto K (2000) Serum arylesterase/diazoxonase activity and genetic polymorphisms in patients with type 2 diabetes. Metabolism 49:1400–1405

  31. 31.

    Stefanovic A, Kotur-Stevuljevic J, Spasic S et al (2010) HDL 2 particles are associated with hyperglycaemia, lower PON1 activity and oxidative stress in type 2 diabetes mellitus patients. Clin Biochem 43:1230–1235

  32. 32.

    Jafarnejad A, Bathaie SZ, Nakhjavani M, Hassan MZ (2008) Effect of spermine on lipid profile and HDL functionality in the streptozotocin-induced diabetic rat model. Life Sci 82:301–307

  33. 33.

    Rosenblat M, Hayek T, Aviram M (2006) Anti-oxidative effects of pomegranate juice (PJ) consumption by diabetic patients on serum and on macrophages. Atherosclerosis 187:363–371

  34. 34.

    Kabay SC, Ozden H, Guven G et al (2009) Protective effects of vitamin E on central nervous system in streptozotocin-induced diabetic rats. Clin Invest Med 32:314–321

Download references

Author information

Correspondence to Ertugrul Uzar.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Uzar, E., Alp, H., Cevik, M.U. et al. Ellagic acid attenuates oxidative stress on brain and sciatic nerve and improves histopathology of brain in streptozotocin-induced diabetic rats. Neurol Sci 33, 567–574 (2012). https://doi.org/10.1007/s10072-011-0775-1

Download citation

Keywords

  • Diabetic brain
  • Nerve
  • Oxidative stress
  • Ellagic acid
  • Neuroprotective