MARKERS OF APOPTOSIS IN CHILDREN WITH VARICELLA, PATHOGENETIC APPROACH TO TREATMENT

Authors

DOI:

https://doi.org/10.11603/1681-2727.2022.1.13022

Keywords:

varicella, chickenpox, apoptosis, caspase-8, AIF, L-arginine

Abstract

The aim of the study was to determine the indicators of apoptosis by intrinsic and extrinsic pathways and possible methods of correction in patients with varicella.

Patients and methods. The study included 150 patients with chickenpox aged 1 month to 17 years hospitalized at the Vinnytsia Regional Clinical Pediatric Infectious Diseases Hospital in 2015-2019. Among the patients formed: comparison group patients with chickenpox who received traditional treatment (n=35), the main group patients with chickenpox who received traditional treatment and L-arginine (n=35), control group healthy children (n=30).

The research was performed in the research clinical and diagnostic laboratory of VNMU certified by the Ministry of Health of Ukraine (certificate of accreditation of the measuring laboratory series KDL No. 002087, certificate of re-certification No. 049/15 of March 2, 2015). Caspase 8 and AIF were determined in serum by enzyme-linked immunosorbent assay using commercial kits «Human CASP8 (Caspase 8) ELISA Kit» («Elabscience Biotechnology Inc.», USA) and «Human AIF (Apoptosis Inducing Factor) ELISA Kit» («Elabscience Biotechnology Inc., USA). The results were analyzed in accordance with the manufacturer’s recommendations.

Results. When assessing the rates of apoptosis in healthy and children with varicella, it was found that in patients with chickenpox serum caspase-8 content increased significantly by 43 % (p<0.05), and AIF content by 37.6 % (p<0.05), compared with a group of healthy children. Having clarified these patterns and considering the information that these indicators can adversely affect the course of the disease and cause complications (due to remodeling and vascular damage), we included in the treatment L-arginine, which affects NO synthesis and can simulate apoptosis process. It was found that in the main group before treatment the median content of caspase-8 is 0.522 (95 % CI 0.488–0.557) ng/ml and AIF 8.17 (95 % CI 7.828.70) pg/ml and after treatment, there was a significant decrease in the mean serum level of caspase-8 by 21.5 % (p<0.05), which was 0.410 (95 % CI 0.2920.531) ng/ml, and AIF by 22.7 % (p<0.05) and was 6.41 (95 % CI 5.68 6.93) pg/ml.

Conclusions. The use of caspase 8 and AIF determination revealed the initiation of a program of apoptosis of cells both extrinsic and intrinsic pathways in patients with varicella. Because of high risk developing vascular remodeling with subsequent complications in patients with varicella, we recommend to include L-arginine in the treatment regimen, which has an antiapoptic effect, which may further prevent complications associated with VZV-vasculopathy.

Author Biographies

I. I. Nezhoda, M. Pyrohov Vinnytsia National Medical University

Assistant at the Department of Pediatric Infectious Diseases, M. Pyrohov Vinnytsia National Medical University, Vinnytsia

L. I. Levytska, Вінницький національний медичний університет ім. М.І. Пирогова

Assistant at the Department of Pediatric Infectious Diseases, M. Pyrohov Vinnytsia National Medical University, Vinnytsia

References

Kramarev, S.A. (2011). Features of the current flow of chickenpox in children. Dytiachyi likar – Pediatrician, 6 (13), 1-4 [in Russian].

Riera-Montes, M., Bollaerts, K., Heininger, U., Hens, N., Gabutti, G., Gil, A., Nozad, B., Mirinaviciute, G., Flem, E., Souverain, A., Verstraeten, T., & Hartwig, S. (2017). Estimation of the burden of varicella in Europe before the introduction of universal childhood immunization. BMC Infectious Diseases, 17 (1), 353. Retrieved from: https://doi.org/10.1186/s12879-017-2445-2

Wu, Chuang, Y.-S., & Lin, Y.-T. (2019). Does Herpes Zoster increase the risk of stroke and myocardial infarction? A comprehensive review. Journal of Clinical Medicine, 8 (4), 547. Retrieved from: https://doi.org/10.3390/jcm8040547

Nagel, M.A., & Bubak, A.N. (2018). Varicella Zoster virus vasculopathy. The Journal of Infectious Diseases, 218 (suppl. 2), S107-S112.

Brazeau, E., Mahalingam, R., Gilden, D., Wellish, M., Kaufer, B. B., Osterrieder, N., & Pugazhenthi, S. (2010). Varicella-zoster virus-induced apoptosis in MeWo cells is accompanied by down-regulation of Bcl-2 expression. Journal of Neurovirology, 16 (2), 133-140. Retrieved from: https://doi.org/10.3109/13550281003682547

Pugazhenthi, S., Gilden, D.H., Nair, S., McAdoo, A., Wellish, M., Brazeau, E., & Mahalingam, R. (2009). Simian varicella virus induces apoptosis in monkey kidney cells by the intrinsic pathway and involves downregulation of bcl-2 expression. Journal of Virology, 83 (18), 9273-82. Retrieved from: https://doi.org/10.1128/JVI.00768-09

James, S.F., Mahalingam, R., & Gilden, D. (2012). Does apoptosis play a role in varicella zoster virus latency and reactivation? Viruses, 4 (9), 1509-14. Retrieved from: https://doi.org/10.3390/v4091509

Diatlova, A.S., Dudkov, A.V., & Linkova, N.S. (2018). Molecular markers of caspase-dependent and mitochondrial apoptosis: Role in the development of pathology and cellular senescence. Uspekhi sovremennoy biologii – Successes of Modern Biology, 138 (2), 126-127 [in Russian].

Staranko, U., Lyuta, M., Peretyatko, Yu., Dacyuk, L., & Sybirna, N. (2010). Influence of nitric oxide on proliferative activity and apoptosis of human peripheral blood mononuclears under x-ray irradiation. VISNYK OF LVIV UNIV. Biology Series, 54, 93-100 [in Ukrainian].

Fosse, J.H., Haraldsen, G., Falk, K., & Edelmann, R. (2021). Endothelial cells in emerging viral infections. Front. Cardiovasc. Med., 8 (619690). DOI: 10.3389/fcvm.2021.619690

Fosse, J.H., Haraldsen, G., Falk, K., & Edelmann, R. (2021). Endothelial cells in emerging viral infections. Front. Cardiovasc. Med., 8 (619690). DOI: 10.3389/fcvm.2021.619690

Published

2022-06-11

How to Cite

Nezhoda, I. I., & Levytska, L. I. (2022). MARKERS OF APOPTOSIS IN CHILDREN WITH VARICELLA, PATHOGENETIC APPROACH TO TREATMENT. Infectious Diseases – Infektsiyni Khvoroby, (1), 66–71. https://doi.org/10.11603/1681-2727.2022.1.13022

Issue

Section

Original investigations