Preview

Transbaikalian Medical Bulletin

Advanced search

Use of 4-hyroxy-3,5-di-tretbutyl cinnamic acid reduces the intensity of neuroinflammation in rats with cerebral ischemia

https://doi.org/10.52485/19986173_2021_1_59

Abstract

The aim of the research. To evaluate the effect of 4-hydroxy-3,5-di-tretbutyl cinnamic acid on neuroinflammation in rats with cerebral ischemia in comparison with ethylmethylhydroxypyridine succinate.

Materials and Methods. Brain ischemia was reproduced in Wistar rats by irreversible right-sided coagulation of the middle cerebral artery. The test-compound-4-hydroxy-3,5-di-tretbutyl cinnamic acid and the reference drug-ethymethylhydroxypyridine succinate were administered orally at a dose of 100 mg / kg 30 minutes after the ischemia modeling and then once a day for 3 days. On the 4th day of the experiment, the degree of permeability of the blood-brain barrier in the Miles test was evaluated. Changes in cytokines (IL- 6; IL-1β; IL-10 and TNF-α) and nitrogen monoxide in brain tissue in animals were also studied. The content of cytokines was determined by enzyme-linked immunoassay, and the concentration of nitrogen monoxide was evaluated spectrophotometrically in reaction with the Griss reagent.

Results. During the study, it was found that the use of the test compound at a dose of 100 mg / kg contributed to a decrease in the concentration of pro-inflammatory cytokines: IL – 6-by 37.2% (p<0.05); IL – 1β-by 42.5% (p<0.05), TNF – α - by 33.4% (p<0.05). At the same time, the content of IL-10 increased by 3.1 (p<0.05). Also, against the background of the administration of 4-hydroxy-3,5-di-tretbutyl cinnamic acid, there was a decrease in the content of nitrogen monoxide in brain tissue and the permeability of the blood-brain barrier by 33.1% (p<0.05) and 38.2% (p<0.05), respectively. It should be noted that the effect of the test compound was superior to that of the reference drug.

Conclusion. 4-hydroxy-3,5-di-tretbutyl cinnamic acid reduces the intensity of neuroinflammatory reactions, which is expressed in a decrease in the content of pro-inflammatory cytokines, the concentration of nitrogen monoxide and the permeability of the blood-brain barrier, which may underlie the neuroprotective effect of this compound.

About the Author

D. I. Pozdnyakov
Pyatigorsk medical and pharmaceutical Institute is a branch of the Volgograd state medical University
Russian Federation

11 Kalinina Ave., Pyatigorsk, Stavropol region, 357532



References

1. Shi L, Rocha M., Leak R.K. A new era for stroke therapy: Integrating neurovascular protection with optimal reperfusion. J Cereb Blood Flow Metab. 2018. 38(12). 2073-2091. doi.10.1177/0271678X18798162

2. Hu X, De Silva T.M., Chen J., Faraci F.M. Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke. Circ Res. 2017. 120(3) .449-471. doi.10.1161/CIRCRESAHA.116.308427

3. Yang C., Hawkins K.E., Doré S., Candelario-Jalil E. Neuroinflammatory mechanisms of blood- brain barrier damage in ischemic stroke. Am J PhysiolCellPhysiol. 2019.316(2). 135-C153. doi.10.1152/ajpcell.00136.2018

4. DiSabato D.J., Quan N., Godbout J.P. Neuroinflammation. the devil is in the details. J Neurochem. 2016.139 Suppl 2(Suppl 2).136-153. doi.10.1111/jnc.13607.

5. Zhou M., Wang C.M., Yang W.L., Wang P. Microglial CD14 activated by iNOS contributes to neuroinflammation in cerebral ischemia. Brain Res. 2013. 1506. 105–114. doi. 10.1016/j.brainres.2013.02.010

6. Wilkins H.M., Swerdlow R.H. TNFα in cerebral ischemia. another stroke against you? Journal of neurochemistry. 2015. 132(4) .369–372. doi. 10.1111/jnc.13028.

7. Murray K.N., Parry-Jones AR, Allan SM. Interleukin-1 and acute brain injury. FrontCellNeurosci. 2015.9.18. doi. 10.3389/fncel.2015.00018.

8. Fahmi R.M., Elsaid A.F. Infarction size, interleukin-6, and their interaction are predictors of short-term stroke outcome in young Egyptian adults. J Stroke Cerebrovasc Dis. 2016. 25(10). 2475–2481. doi. 10.1016/j.jstrokecerebrovasdis.2016.06.021.

9. Terpolilli N.A., Moskowitz M.A., Plesnila N. Nitric oxide: considerations for the treatment of ischemic stroke. J CerebBloodFlowMetab. 2012. 32(7). 1332–1346. doi. 10.1038/jcbfm.2012.12.

10. Nam M.H. Excessive Astrocytic GABA Causes Cortical Hypometabolism and Impedes Functional Recovery after Subcortical Stroke. Cell reports. 2020. 32 (1). 107861

11. Bechter K. The Challenge of Assessing Mild Neuroinflammation in Severe Mental Disorders. Front Psychiatry. 2020. 11. 773 doi.10.3389/fpsyt.2020.00773

12. Yuan Y., Zha H., Rangarajan P., Ling E.A., Wu C. Anti-inflammatory effects of Edaravone and Scutellarin in activated microglia in experimentally induced ischemia injury in rats and in BV-2 microglia. BMC Neurosci. 2014. 15. 125. doi. 10.1186/s12868-014-0125-3.

13. Duan J., Cui J., Yang Z. Neuroprotective effect of Apelin 13 on ischemic stroke by activating AMPK/GSK-3β/Nrf2 signaling. J Neuroinflammation. 2019. 16(1). n24.

14. Voronkov A.V., Pozdnyakov D.I., Khuri E.I., Kulbekova Yu.E., Kobin A.A. Evaluation of the antioxidant activity of 4-hydroxy-3,5-ditretbutyl cinnamic acid, Mexidol, and thioctic acid on a model of focal brain ischemia. Questions of biological, medical and pharmaceutical chemistry. 2017. 20(2). 48-52. in Russian

15. Radu M., Chernoff J. An in vivo assay to test blood vessel permeability. J Vis Exp. 2013.(73).e50062. Published 2013 Mar 16. doi.10.3791/50062

16. Muhammad T, Ikram M, Ullah R., Rehman S.U., Kim M.O. Hesperetin, a Citrus Flavonoid, Attenuates LPS-Induced Neuroinflammation, Apoptosis and Memory Impairments by Modulating TLR4/NF-κB Signaling. Nutrients. 2019. n11(3). n648. Published 2019 Mar 17. doi.10.3390/nu11030648

17. Pozdnyakov D.I., Voronkov A.V., Zolotych D.S. Possible mechanisms of endothelioproteсtion 4-hydroxy-3,5-di-tretbutyl cinnamic acid in the cerebral ischemia in experiment International Journal of Toxicological and Pharmacological Research. 2018. 10(2). 189-193.

18. Voronkov A.V., Pozdnyakov D.I., Zolotykh D.S., Efremova M.P. Effect of atacl compound on the anti-inflammatory potential of the endothelium of rat brain vessels in experimental ischemia. Crimean therapeutic journal. 2017. 4 (35). 60-63. in Russian.

19. Lepeta K., Kaczmarek L. Matrix Metalloproteinase-9 as a Novel Player in Synaptic Plasticity and Schizophrenia. Schizophr Bull. 2015. 41(5). 1003-1009. doi.10.1093/schbul/sbv036

20. Wajant H. TRAIL- and TNF-induced signaling complexes-so similar yet so different. EMBO J. 2017 .36(9).1117-1119.


Review

For citations:


Pozdnyakov D.I. Use of 4-hyroxy-3,5-di-tretbutyl cinnamic acid reduces the intensity of neuroinflammation in rats with cerebral ischemia. Transbaikalian Medical Bulletin. 2021;(1):59-67. (In Russ.) https://doi.org/10.52485/19986173_2021_1_59

Views: 90


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1998-6173 (Online)