Basic Requirements And Features Of Methodology Of The Vascular Permeability Model

DOI: 10.29296/2618723X-2018-03-06

D.S. Gajdaj(1), E.A. Gajdaj(1), K.L. Kryshen(2), М.N. Makarova(3), V.G. Makarov(3) 1-Institute of pre-clinical studies Leningradskiy region, Vsevolozhskiy district, Kuzmolovskiy, Zavodskaya st., b. 3, 245, 188663, Russia; 2-St.Petersbug institute of pharmacy Leningradskiy region, Vsevolozhskiy district, Kuzmolovskiy, Zavodskaya st., b. 3, 245, 188663, Russia; 3-Scientific-Production Organization «Houm оf Pharmacy» Leningradskiy region, Vsevolozhskiy district, Kuzmolovskiy, Zavodskaya st., b. 3, 245, 188663, Russia; Е-mail: [email protected]

Keywords: pre-clinical studies vascular permeability compound 48/80 Evans blue dye
For citation:

Gajdaj D.S., Gajdaj E.A., Kryshen K.L., Makarova М.N., Makarov V.G. Basic Requirements And Features Of Methodology Of The Vascular Permeability Model. Laboratory Animals for Science. 2018; 3. https://doi.org/10.29296/2618723X-2018-03-06

Abstract

This model is used to evaluate the inhibitory activity of drugs aimed at vascular permeability normalization. The barrier function of endothelium is disrupted on some pathologies. The factors affecting an acute increase vascular permeability include natural agents such as thrombin, histamine, bradykinin, reactive oxygen and nitrogen, vascular endothelial growth factor (VEGF), tumor necrosis factor, bacterial endotoxins, necrotic toxins and excessive mechanical stimulation. As a consequence, fluid and plasma proteins are extravasated and edemas are formed. These effects are counteracted by H1-antihistaminics, inhibitors of arachidonic acid metabolism, by leukotriene receptor antagonists and membrane stabilizing drugs are able to reduce capillary permeability. In experiment vascular permeability is increased by intracutaneous injection of the mast cell-degranulating compound 48/80. The vascular permeability can be assessed by Evans blue dye. The main requirements and peculiarities of methodology of vessels permeability model are considered in the article. Within this model, increase in vascular permeability is caused by intradermal injection of compound 48/80, and is confirmed by infiltration of Evans blue dye into the injected skin areas. The vessels permeability is assessed by measuring diameter of colored skin areas and extracting of Evans blue dye. The experimental model shows that intradermal administration of compound 48/80 leads to increase in the permeability of rat skin vessels. The standard object phenylephrine with intraperitoneal administration to rats at a dose 15 mg/kg statistically significant reduces vascular permeability. The dose of Evans blue dye optimal for this type of the study and the time interval at which noted the maximum concentration of dye in tissue, were determined. Based on the results of the studies, it can be concluded that this model is simple, uncomplicated and quite informative.

References

  1. Garbuzenko D.V. Mehanizmy adaptacii sosudistogo rusla k gemodinamicheskim narusheniyam pri portal`noy gipertenzii. Vestnik RAMN. 2013; 1: 52–7.
  2. Direktiva 2010/63/EU Evropeyskogo Parlamenta i Soveta Evropeyskogo Soyuza po ohrane zhivotnyh, ispol`zuemyh v nauchnyh celyah. NP «Ob``edinenie specialistov po rabote s laboratornymi zhivotnymi» (Rus-LASA). SPb. 2012: 48.
  3. Shirinskiy V.P. Molekulyarnaya fiziologiya e`ndoteliya i mehanizmy pronicaemosti sosudov. Uspehi fiziol. nauk. 2011; 42 (1): 18–32.
  4. Bennett A.J., G.B. West. Measurement of the changes in vascular permeability in rat skin. Journal of Pharmacological and Toxicological Methods. 1978; 1: 105–8.
  5. Huang H., Bhat A., Woodnutt G. et al. Targeting the ANGPT-TIE2 pathway in malignancy. Nature Reviews Cancer. 2010; 10 (8): 575–85.
  6. Katayama S., Shionoya H., Ohtake S. A new method for extraction of extravasated dye in the skin and the influence of fasting stress on passive cutaneous anaphylaxis in guinea pigs and rats. Microbiology and Immunology. 1978; 22 (2): 89–101.
  7. Lawrence A.C.K., Walters G. The extraction of Evans blue (T1824) from plasma and the measurement of plasma volume. Journal of Clinical Pathology. 1959; 12: 123.
  8. Ramesh B.N., Mahalakshmi A.M., Mallappa S. Vascular permeability and Evans blue dye a physiological and pharmacological approach. Journal of Applied Pharmaceutical Science. 2014; 4 (11): 106–13.
  9. Tsopelas C., Sutton R. Why certain dyes are useful for localizing the sentinel lymph node. The Journal of Nuclear Medicine. 2002; 43 (10): 1377–82.
  10. Vogel H.G. Drug Discovery and Evaluation:Pharmacological Assays. Springer. 2008.
  11. Wang H.-L., Lai T.W. Optimization of Evans blue quantitation in limited rat tissue samples.Scientific Reports.2014; 4: 6588.
  12. E`lektronnyy resurs: http://bono-esse.ru/blizzard/RPP/M/Infekcionka/pronicaemost_ kapilljarov.html
  13. E`lektronnyy resurs: http://www.ysam.ru/kras/80.html
  14. E`lektronnyy resurs: https://www.rlsnet.ru/mnn_index_id_931.htm

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