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BioNanoScience

, Volume 9, Issue 1, pp 224–234 | Cite as

Pyrimidine Derivative Ameliorates Spinal Cord Injury via Anti-apoptotic, Anti-inflammatory, and Antioxidant Effects and by Regulating Rho GTPases

  • Tatyana V. PovyshevaEmail author
  • Syumbel R. Sabirova
  • Michael S. Shashin
  • Irina V. Galyametdinova
  • Vyacheslav E. Semenov
  • Yuri A. Chelyshev
Article
  • 32 Downloads

Abstract

One of the most important strategies for the treatment of spinal cord injury is searching for new and effective pharmacological neuroprotectors and regeneration stimulators. The derivatives of pyrimidine are universal stimulators of the regeneration of various tissues as they support the recovery of nervous structures. The protective effect of the cocrystal of 1,2-dihydro-4,6-dimethyl-1-(2-hydroxyethyl)-pyrimidinone-2 with para-aminobenzoic acid (compound conjugate III, CCIII) was explored on a rat model with a contusion spinal cord injury. Injection of CCIII significantly reduced the expression of tumor necrosis factor α (TNF-α), inhibited the synthesis of myeloperoxidase (MPO), matrix metalloproteinase 9 (MPP9), cyclooxygenase-2 (COX2), and macrophage marker CD68, and increased the level of superoxide dismutase 1 (SOD1). Additionally, the expression of caspase-7 markers in the damaged tissue decreased under the action of CCIII. Treatment with the CCIII maintained a population of Olig2-positive myelin-forming cells at 30 days post-injury. The detected therapeutic effect is comparable with that of riluzole.

Keywords

Spinal cord injury Pyrimidine derivative Riluzole TNF-α SOD1 Rho GTPases Antiinflammatory drugs 

Notes

Acknowledgements

We would like to thank D. N. Fattakhova, Kazan State Medical University (Kazan, Russia) for their assistance in some experiments.

Funding

This work was funded by grant №14-50-00014 from the Russian Science Foundation and supported by Program of Competitive Growth of KFU.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Kazan Federal UniversityKazanRussia
  2. 2.Kazan State Medical UniversityKazanRussia
  3. 3.A.E. Arbuzov Institute of Organic and Physical Chemistry Kazan Scientific CenterRussian Academy of ScienceKazanRussia

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