Neuroprotective effects of α-lipoic acid on the development of oxidative stress and astrogliosis in the brain of STZ-diabetic rats


  • S. Kyrychenko Oles Honchar Dnipropetrovsk National University
  • I. Prishchepa Oles Honchar Dnipropetrovsk National University
  • V. Lagoda Oles Honchar Dnipropetrovsk National University
  • M. Velika Oles Honchar Dnipropetrovsk National University
  • V. Nedzvetsky Oles Honchar Dnipropetrovsk National University
Keywords: streptozotocin (STZ), alpha-lipoic acid (alpha-LA), glial fibrillary acidic protein, lipid peroxidation

Abstract

The aim of this study was to examine whether the antioxidant alpha-lipoic acid protects neurons from diabetic-reperfusion injury. The streptozotocin (STZ) rat model was used to study the glial reactivity and prevention of gliosis by alpha-lipoic acid (alpha-LA) administration. The expression of glial fibrillary acidic protein (GFAP) was determined, as well as lipid peroxidation (LPO) and glu-tathione (GSH) levels in some brain tissues. We observed significant increasing of lipid peroxidation products in both hippocampus and cortex. Changesof polypeptide GFAP were observed in hippocampus and cortex. Both soluble and filamentous forms of GFAP featured the increase in hippocampus of rat with hyperthyreosis. In the filamentfractions, increase in the intensity of 49 kDa polypeptide band was found. In the same fraction of insoluble cytoskeleton proteins degraded HFKB polypeptides with molecular weight in the range of 46–41 kDa appeared. Markedincrease of degraded polypeptides was found in the soluble fraction of the brain stem. The intensity of the intact polypeptide – 49 kDa, as well as in the filament fraction, significantly increased. It is possible that increasing concentrations of soluble subunits glial filaments may be due to dissociation of own filaments during the reorganization of cytoskeleton structures. Given the results of Western blotting for filament fraction, increased content of soluble intact 49 kDa polypeptide is primarily the result of increased expression of HFKB and only partly due to redistribution of existing filament structures. Calculation and analysis of indicators showed high correlation between the increase in content and peroxidation products of HFKB.These results indicate the important role of oxidative stress in the induction of astroglial response under conditions of diabet encefalopathia. Administration of alpha-LA reduced the expression both of glial and neuronal markers. In addition, alpha-LA significantly prevented the increase in LPO levels found in diabetic rats. GSH levels increased by the administration of alpha-LA. This study suggests that alpha-LA prevents neural injury by inhibiting oxidative stress and suppressing reactive gliosis. All these changes were clearly counteracted by alpha-lipoic acid. The results of this study demonstrate that alpha-lipoic acid provides for protection to the GFAP, as a whole, from diabet -reperfusion injuries. 

References

Baydas, G., Donder, E., Kiliboz, M., Sonkaya, E., Tuzcu, M., Yasar, A., Nedzvetskii, V.S., 2004. Neuroprotection by α-lipoic acid in streptozotocin-induced diabetes. Biochemistry (Moscow) 69(9) 1233–1238.
Bernal, J., Nunez, J., 1995. Thyroid hormones and brain development. Eur. J. Endocrinol. 133(4), 390–398. >>doi: 10.1530/eje.0.1330390
Bonnefont-Rousselot, D., 2004. The role of antioxidant micronutrients in the prevention of diabetic complications. Treat Endocrinol. 3(1), 41–52. >>doi: 10.2165/00024677-200403010-00005
Bruckner, I., Bustan, C., Adamescu, E., Dobjanschi, C., 2002. Diabetic neuropathy-choices of treatment. Rom. J. Intern. Med. 40(1–4), 53–60.
Eng, L.F., 2000. Glial fibrillary acidic protein: GFAP-thirty-one years (1969–2000). Neurochem. Res. 25(9–10), 1439–1451. >>doi: 10.1023/A:1007677003387
Gandhi, G.K., Ball, K.K., Cruz, N.F., Dienel, G.A., 2010. Hyperglycaemia and diabetes impair gap junctional communication among astrocytes. ASN Neuro 15(2), e00030. >>doi: 10.1042/AN20090048
Gonzalez-Perez, O., Gonzalez-Castaneda, R.E., Huerta, M., Luquin, S., Gomez-Pinedo, U., Sanchez-Almaraz, E., Navarro-Ruiz, A., Garcia-Estrada, J., 2002. Beneficial effects of alpha-lipoic acid plus vitamin E on neurological deficit, reactive gliosis and neuronal remodeling in the penumbra of the ischemic rat brain. Neurosci. Lett. 321(1–2), 100–104. >>doi: 10.1016/S0304-3940(02)00056-3
Graham, D.G., 1999. Neurotoxicants and the cytoskeleton. Curr. Opin. Neurol. 12(6), 733–737. >>doi: 10.1097/00019052-199912000-00013
Lepekhin, E.A., Eliasson, C., Berthold, C.H., Berezin, V., Bock, E., Pekny, M., 2001. Intermediate filaments regulate astrocyte motility. J. Neurochem. 79(3), 617–625.
O'Callaghan, J.P., Jensen, K.F., Miller, D.B., 1995. Quantitative aspects of drug and toxicant-induced astrogliosis. Neurochem. Int. 26(2), 115–124. >>doi: 10.1016/0197-0186(94)00106-5
Panickar, K.S., Jayakumar, A.R., Rama Rao, K.V., 2007. Downregulation of the 18-kDa translocator protein: Effects on the ammonia-induced mitochondrial permeability transition and cell swelling in cultured astrocytes. Glia 55(16), 1720–1727. >>doi: 10.1002/glia.20584
Pekny, M., Pekna, M., 2004. Astrocyte intermediate filaments in CNS pathologies and regeneration. J. Pathol. 204(4), 428–437. >>doi: 10.1002/path.1645
Poon, H.F., Farr, S.A., Thongboonkerd, V., Lynn, B.C., Banks, W.A., Morley, J.E., Klein, J.B., Butterfield, D.A., 2005. Proteomic analysis of specific brain proteins in aged SAMP8 mice treated with alpha-lipoic acid: Implications for aging and age-related neurodegenerative disorders. Neurochem. Int. 46(2), 159–168. >>doi: 10.1016/j.neuint.2004.07.008
Rose, C., 2006. Effect of ammonia on astrocytic glutamate uptake/release mechanisms. J. Neurochem. 97, 11–15. >>doi: 10.1111/j.1471-4159.2006.03796.x
Song, K.H., Lee, W.J., Koh, J.M., Kim, H.S., Youn, J.Y., Park, H.S., Koh, E.H., Kim, M.S., Youn, J.H., Lee, K.U., Park, J.Y., 2005. alpha-Lipoic acid prevents diabetes mellitus in diabetes-prone obese rats. Biochem. Biophys. Res. Commun. 326(1), 197–202.
Yang, Z., Li, K., Yan, X., Dong, F., Zhao, C., 2010. Amelioration of diabetic retinopathy by engrafted human adipose-derived mesenchymal stem cells in streptozotocin diabetic rats. Graefes. Arch. Clin. Exp. Ophthalmol. 2, 345–349. >>doi: 10.1007/s00417-010-1384-z
Published
2014-07-12
How to Cite
Kyrychenko, S., Prishchepa, I., Lagoda, V., Velika, M., & Nedzvetsky, V. (2014). Neuroprotective effects of α-lipoic acid on the development of oxidative stress and astrogliosis in the brain of STZ-diabetic rats. Regulatory Mechanisms in Biosystems, 5(2), 143-147. https://doi.org/https://doi.org/10.15421/021427