Nitrosorbidi Stress and Apoptosis of Neurons in the CA1 Zone of the Hippocampus in the Conditions of Modeling Chronic Alcohol Intoxication: Neuroprotective Effects of Tietema

T. Kucher; L. Kucherenko; S. Morguntsova

doi:10.12737/5906

NITROSORBIDI STRESS AND APOPTOSIS OF NEURONS IN THE CA1 ZONE OF THE HIPPOCAMPUS IN THE CONDITIONS OF MODELING CHRONIC ALCOHOL INTOXICATION: NEUROPROTECTIVE EFFECTS OF TIETEMA Nitrosorbidi Stress and Apoptosis of Neurons in the CA1 Zone of the Hippocampus in the Conditions of Modeling Chronic Alcohol Intoxication: Neuroprotective Effects of Tietema

АА Аа

Published in Journal of New Medical Technologies · Volume 21, Issue 3 · Pages 85–91 · Rubric: Clinical Picture and Methods of Treatment. Functional and Instrumental Diagnostics. New Medicinal Forms

DOI: https://doi.org/10.12737/5906

Received: 06.10.2014 Accepted: 06.10.2014 Published: 06.10.2014 Language of publication: RUS

Authors

T. Kucher

L. Kucherenko

S. Morguntsova

T. Kucher

L. Kucherenko

S. Morguntsova

ABSTRACT

Fulfilled researches showed that modeling of chronic alcohol intoxication by daily intragastric ethanol administration to non-pedigreed male white rats (first 10 days – 15% ethanol solution in dose 4 g/kg, next 10 days – 15% ethanol solution in dose 6 g/kg, then 10 days – 25% ethanol solution in dose 4 g/kg) leads to activation of nitrosorbidi stress reactions and initiation of neuro-apoptosis. Thus, as compared with healthy animals group, in rats’ brain after chronic ethanol administration it was revealed significant increase of nitro-tyrosine (nitrosorbidi stress marker) in cytosolic and mitochondrial fractions of brain homogenate against the background of revealing of apoptosis molecular markers in hippocampal CA1 zone neurons (fragmentation of neuron´s nuclei of hippocampal CA1 zone, increase of density and ratio of apoptotic- and destructive-changed cells) as well as deprivation of anti-apoptotic mechanisms (decrease of density of Bcl-2-positive neurons in hippocampal CA1 zone and decrease of Bcl-2 protein concentration in hippocampus). Subsequent 14-day intragastric administration of complex neuro-metabolic cerebro-protector Thiocetam in dose 100 mg/kg to the animals after chronic alcoholization showed significant protective effect on hippocampal CA1 zone neurons. Thus, Thiocetam administration resulted in decrease of nitrotyrosine levels in mitochondrion and in cytosol of brain of animals with chronic alcoholization as compared with untreated animals and with animals receiving Piracetam. Thiocetam administration to experimental animals led to significant decrease of density of apoptotic- and destructive-changed neurons of hippocampal CA1 zone and ratio of apoptotic-changed cells as compared with control group and animals receiving Piracetam. Course of treatment with Thiocetam increases significantly the density of Bcl-2-positive neurons in CA1 zone of hippocampus and significantly increases concentration of Bcl-2 in brain tissue of experimental animals as compared with control group and animals which received Piracetam according the same schedule. The increase of Bcl-2 protein expression in animals received Thiocetam testifies to the activation of anti-apoptotic defense of damaged neurons under the influence of this preparation. We suppose that one of the molecular mechanisms of neuro-protective effect of Thiocetam in chronic intoxication is the breaking of NO-depended mechanisms of neuro-apoptosis.

KEYWORDS

Thiocetam, Piracetam, chronic alcoholism, neuro-apoptosis, hippocampus, nitrosorbidi stress.

1. Belenichev I.F., Cherniy V.I., Kolesnik Yu.M. Ra-tsional´naya neyroprotektsiya. Donetsk: Izd-l´ Zaslavskiy A.Yu. 2009. 248 s.

2. Belenichev I.F., Pavlov S.V., Sokolik E.P., Bukhtiyarova N.V. Novye vozmozhnosti lecheniya alkogol´noy bolezni. Perspektivy primeneniya tserebrokurina. Mezhdunarodnyy nevrologicheskiy zhurnal. 2009. №1(29). S. 116-128.

3. Belenichev I.F. , Fil´yanskiy E.O., Pavlov S.V., Bukhtiyarova N.V. , Kucherenko L.I., Egorov A.N. Vliyanie tiotsetama na pokazateli energeticheskogo metabolizma i sopryazhennogo s nim GAMK-shunta v golovnom mozge potomstva, rozhdennogo ot alkogol´zavisimykh materey. Zaporozhskiy meditsinskiy zhurnal. 2010. Tom 12. №5. S. 127-130.

4. Belenichev I.F., Chekman I.S., Gubskiy Yu.I. Doklinicheskoe izuchenie spetsificheskoy aktivnosti potentsial´nykh neyroprotektivnykh preparatov. Metodicheskie rekomendatsii Gosudarstvennogo Farmakologicheskogo Tsentra MZ Ukrainy. Kiev, 2010. 81 s.

5. Belenichev I.F., Bukhtiyarova N.V., Volkov V.P. Far-makologiya: kollektivnaya nauchnaya monografiya. Novosi-birsk: Izd. «SibAK», 2013. 194 s.

6. Belenichev I.F., Chekman I.S., Bukhtiyarova N.V., Gorbacheva S.V. Tiol-disul´fidnoe ravnovesie - opredelyayushchiy opredelyayushchiy faktor rezistentnosti neyronov k nitroziruyushchemu stressu v usloviyakh ishemii mozga. Zhurnal NAMN Ukraїni. 2013. T. 19. № 1. S. 3-11.

7. Gershteyn L.M., Korneva I.M., Rakhmanova V.I. Morfokhimicheskie osbennosti neyronov gippokampa u krys, razlichayushchikhsya po povedeniyu. Byul. eksperim. biologii i meditsiny. 2007. T. 144. №12. S. 696-698.

8. Egorov A.N., Belenichev I.F., Sokolik E.P. Sostoyanie glutationovoy sistemy golovnogo mozga prenatal´no alkogolizirovannykh krys na fone kursovogo naznacheniya tserebrokurina i tiotsetama. Farmakologiya i vrachebnaya toksikologiya. 2012. №. 2(27). C. 36-39.

9. Mazur I.A., Voloshin N.A., Belenichev I.F. Tiot-riazolin, tiodaron v lechenii serdechno-sosudistykh pato-logiy. Zaporozh´e: Pechatnyy Mir, 2012. 300 s.

10. Al-Moundhri M., Nirmala V., Al-Mawaly K. Al-Moundhri M. Significance of p53, Bcl-2, and HER-2/neu protein expression in Omani Arab females with breast cancer. Pathol Oncol Res. 2011. Vol. 9. №. 4. P. 226-231.

11. Bassik M.C. Exercise-induced Bcl-2-regulated autophagy is required for muscle glucose homeostasis. Nature. 2012. Vol.18. №.481(7382). P. 511-535.

12. Belenichev I.F., Sokolik E.P. Nitrozine stress and neurological discorders in experimental alcohol intoxication and their pharmacological correction by neuropeptides. Inventi Rapid Molekular Pharmacology. 2011. №4. P. 11-18.

13. Belenichev I.F.,Sokolik E.P., Abramov A.V. Pharmacological modulation of apoptosis signaling in neurons of CA1-zone of hippocampus of rats with chronic alcohol intoxication. Innovative Journal of Medical and Health Science. 2011. Vol.1. №1. P. 12-16.

14. Belenichev I.F., Egorov A., Sokolik A. The impact of neurotrophic cerebroprotection on the expression of hsp70 in the brain of rats with prenatal chronic alcoholism. Conference: XXVIth International Symposium on Cerebral Blood Flow, Metabolism and Function & XIth International Conference on Quantification of Brain Function with PET Shanghai, China, May 20. 23. 2013. R.591

15. Ben-Neriah S. Concurrent expression of MYC and bcl-2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J. Clin. Oncol. 2012. Vol 1. №30(28). P. 34-52

16. Boghaert E.R. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013. Vol.19. №2. P. 220-228.

17. Chertin B., Rolle U., Farkas H. The role of nitric oxide in reflux nephropathy. Pediatr Surg Int. 2009. Vol. 18. P. 630-634.

18. Chen R.M., Tai Y.T., Chen T.G., Lin T.H., Chang H.C., Chen T.L., Wu G.J. Chen R.M. Propofol protects against nitrosative stress-induced apoptotic insults to cerebrovascular endothelial cells via an intrinsic mitochondrial mechanism. Surgery. 2013. Vol.6. №1(154). P. 58-68.

19. Neelam A. Role of oxidative/nitrosative stress-mediated Bcl-2 regulation in apoptosis and malignant trans-formation. Annals of the New York Academy of Sciences. 2010. Vol.8. №1203. P. 1-6.

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Editor-in-Chief, editorial board chair

GOST

Kucher T., Kucherenko L., Morguntsova S. Nitrosorbidi Stress and Apoptosis of Neurons in the CA1 Zone of the Hippocampus in the Conditions of Modeling Chronic Alcohol Intoxication: Neuroprotective Effects of Tietema // Journal of New Medical Technologies. 2014. no. 3. pp. 85-91. DOI: https://doi.org/10.12737/5906. (Date of access 02.10.2026).

MLA

T. Kucher, Kucherenko L., Morguntsova S.. "Nitrosorbidi Stress and Apoptosis of Neurons in the CA1 Zone of the Hippocampus in the Conditions of Modeling Chronic Alcohol Intoxication: Neuroprotective Effects of Tietema." Journal of New Medical Technologies 21.3 (2014): 85-91. DOI: https://doi.org/10.12737/5906.

APA

Kucher T., Kucherenko L., Morguntsova S. (2014). Nitrosorbidi Stress and Apoptosis of Neurons in the CA1 Zone of the Hippocampus in the Conditions of Modeling Chronic Alcohol Intoxication: Neuroprotective Effects of Tietema. Journal of New Medical Technologies, 21(3), 85-91. https://doi.org/10.12737/5906

Chicago

T. Kucher, Kucherenko L., Morguntsova S.. "Nitrosorbidi Stress and Apoptosis of Neurons in the CA1 Zone of the Hippocampus in the Conditions of Modeling Chronic Alcohol Intoxication: Neuroprotective Effects of Tietema." Journal of New Medical Technologies 21, no. 3 (2014): 85-91. https://doi.org/10.12737/5906.

WIKI

{{cite journal | author = Kucher T., Kucherenko L., Morguntsova S. | title = Nitrosorbidi Stress and Apoptosis of Neurons in the CA1 Zone of the Hippocampus in the Conditions of Modeling Chronic Alcohol Intoxication: Neuroprotective Effects of Tietema | journal = Journal of New Medical Technologies | year = 2014 | volume = 21 | issue = 3 | pages = 85-91 | doi = 10.12737/5906 }}

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