Preview

Tuberculosis and socially significant diseases

Advanced search

STUDY OF CYTOTOXICITY AND ANTIBACTERIAL ACTIVITY OF HIKSOZID

Abstract

The anti-tuberculosis activity of Hiksozid versus Isoniazid was studied in vivo and their effect on the on the generation of antituberculosis and anti-drug antibodies in inoculated animals. M. tuberculosis H37Rv-infected mice given inhaled Hiksozid 2 and 4 weeks after initiation of therapy, as compared to the control ones, showed was a significant drop in MBT CFU in the lung. At 56 day of the study, there was a significant rise in anti-tuberculosis IgG2a antibody titers in the Hiksozid group as compared to the inoculated control group whereas the titers and levels of IgG2a antibodies increased during Isoniazid therapy. Hiksozid therapy leads to an increase in the titer of anti-tuberculosis antibodies, but not in their levels, as observed during Isoniazid therapy. Investigation of an anti-drug response to the conjugates of Isoniazid demonstrated the presence of IgG antibodies that increased during therapy with Hiksozid and isoniazid (at day 56), their affinity and avidity rose particularly during Hiksozid therapy. At the same time, there were rises in the titers and levels of anti-isoniazid IgG1 and the levels of anti-isoniazid IgG2b antibodies whereas a response to dioxidin was observed due to the increased titers and level of IgG2b. In the groups of inoculated animals treated with isoniazid and Hiksozid, the higher titers and level of IgG2b against dioxidin are indicative of a cross and nonspecific response to this drug, which occurs after inoculation. According to histological and biochemical studies, inhalational administration Hiksozid intact mice has no adverse effects on the structure of the lung parenchyma, and the infected animals shows a marked positive effect on the dynamics of the processes of healing foci of inflammation in the lungs and restore the structural and functional characteristics.

About the Authors

V. Ya. Gergert
ФГБУ «Центральный научно-исследовательский институт туберкулеза РАМН»
Russian Federation


O. A. Popova
ООО «Мир-Фарм»
Russian Federation


References

1. Манухов И. В., Котова В. Ю., Мальдов Д. Г. и др. Индукция окислительного стресса и SOS-ответа в бактериях Escherichia coli растительными экстрактами: роль гидроперекисей и эффект синергизма при совместном действии с цисплатиной // Микробиология. – 2008. – Т. 77. – № 5. – С. 1–8.

2. Манухов И. В., Котова В.Ю., Завильгельский Г. Б. Lux-биосенсоры для детекции SOS-ответа, теплового шока и окислительного стресса // Биотехнология. – 2009. – № 6. – С. 16-25.

3. Отраслевые показатели противотуберкулезной работы в 2010-2011 гг. Статистические материалы и аналитический обзор основных показателей.– М.: ООО «Колор Медиа», 2013. – 48 с.

4. Engvall E., Perlmann P. Enzyme-linked immunosorbent assay (ELISA). Quantitative assay of immunoglobulin G // Immunochemistry. – 1971. – Vol. 8. – N. 9. – P. 871-874.

5. Gadek J.E., Fells G.A., Zimmerman R.L., Crystal R.G. Role of connective tissue proteases in the pathogenesis of chronic inflammatory lung disease: review // Environ. Health Perspect. – 1984. – Vol. 55. – N. 4. – P. 297-306.

6. Global tuberculosis report 2012.- WHO (WHO/HTM/TB/ 2012.6). – 98 p.

7. Kapina M.A., Shepelkova G.S., Mischenko V.V. et al. CD27low CD4 T-lymphocytes that accumulate in the mouse lungs during mycobacterial infection differentiate from CD27high precursors in situ, produce IFN-gamma, and protect the host against tuberculosis infection // J. Immunol. – 2007. – Vol. 178. – N. 2. - P. 976-985.

8. Lyadova I.V., Oberdorf S., Kapina M.A. et al. CD4 T cells producing IFN-gamma in the lungs of mice challenged with mycobacteria express a CD27-negative phenotype // Clin. exp. Immunol. – 2004. – Vol. 138. – N. 1. – P. 21-29.

9. Twining S. S. Fluorescein isothiocyanate-labeled casein assay for proteolytic enzymes // Anal. Biochem. – 1984. – Vol. 143. – N. 1. – P. 30–34.

10. Zavilgelsky G.B., Kotova V.Yu., Manukhov I.V. Action of asymmetric 1,1-dimethylhydrazine on bacterial cells is determined by hydrogen peroxide // Mutation Res. – 2007. – Vol. 634. – N. 1-2. – P. 172-176.


Review

For citations:


Gergert V.Ya., Popova O.A. STUDY OF CYTOTOXICITY AND ANTIBACTERIAL ACTIVITY OF HIKSOZID. Tuberculosis and socially significant diseases. 2014;(4):18-31. (In Russ.)

Views: 29


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


ISSN 2413-0346 (Print)
ISSN 2413-0354 (Online)