The donor of carbon monoxide (CORM-2) affects the level of serum immunoglobulins and the state of the bone marrow during the immune response in mice

Authors

DOI:

https://doi.org/10.14739/2409-2932.2020.3.216229

Keywords:

gas transmitter, carbon monoxide, CORM-2, humoral immune response

Abstract

 

Toxic carbon monoxide in small concentrations has pro-apoptotic, anti-allergic, vasodilator effects, and stimulates angiogenesis. The problem with the therapeutic use of low doses of carbon monoxide is that it is difficult to dose. To control the amount and gradual release of carbon monoxide, non-toxic preparation is used - CO donor based on carbonyl compound of ruthenium (CORM-2).

The aim – is to identify the effect of CORM-2 on the level of immunoglobulins in the blood serum and bone marrow of mice under conditions of inducing an immune response.

Materials and methods. 3 groups of 15 white laboratory mice each were formed. Induction of the immune response was due to the intraperitoneal administration of xenogenic red blood cells. The first experimental group on the first day of immunization received CORM-2 (20 mg/kg), group No. 2 – on the 5th day after immunization (period of the productive phase). The control group consisted of immunized animals that did not receive CORM-2. The amount of IgA, IgM, and IgG in blood serum was determined by ELISA on the 2nd and 6th day after immunization. At the end of the experiment, bone marrow cell populations were counted.

Results. After the injection of CORM-2 during the induction phase of the immune response, it inhibits the production of immunoglobulins. In comparison with the control, the level of IgA and IgG is reduced, but the amount of IgM remains unchanged. In the bone marrow, the number of monocytes, erythroblasts, and normoblasts, as well as lymphoblasts and plasma cells, increased. At the same time, the number of myeloblasts, myelocytes, basophilic normoblasts, and megakaryocytes decreased. The use of CORM-2 during the productive phase caused a decrease in the level of IgM and IgG with a simultaneous increase in the level of IgA. The number of neutrophils, eosinophils, monocytes, polychromophilic and oxyphilic normoblasts, lymphocytes, and plasma cells in the bone marrow increased. However, the number of myeloblasts, promyelocytes, myelocytes, metamyelocytes, basophilic normoblasts, and megakaryocytes decreased.

Conclusions. The impact of the CORM-2 on the inductive phase of the immune response leads to inhibition of the production of immunoglobulins. The injection of CORM-2 during the productive phase of the immune response decreased the level of IgM and IgG, but at the same time, an increase in the level of IgA was observed. After the injection of CORM-2, in the bone marrow, the number of monocytes, lymphocytes, and plasma cells increased. The results indicate that CORM-2 is able to modulate the immune response.

 

References

Gladka, I. V., & Shkuropat, A. V. (2016). Efektyvnist khimichnykh ta biolohichnykh metodiv preventsii rozvytku bakterioziv plodiv Capsicum anuum [Effectiveness of chemical and biological methods of prevention of bacteriosis Capsicum anuum]. Pryrodnychyi almanakh. Seria: Biolohichni nauky, (23), 13-19. [in Ukrainian]. http://na.kspu.edu/index.php/na/article/view/462

Fayad-Kobeissi, S., Ratovonantenaina, J., Dabiré, H., Wilson, J. L., Rodriguez, A. M., Berdeaux, A., Dubois-Randé, J., Mann, B., Motterlini, R., & Foresti, R. (2016). Vascular and angiogenic activities of CORM-401, an oxidant-sensitive CO-releasing molecule. Biochemical Pharmacology, 102, 64-77. https://doi.org/10.1016/j.bcp.2015.12.014

Ji, X., Damera, K., Zheng, Y., Yu, B., Otterbein, L. E., & Wang, B. (2016). Toward Carbon Monoxide-Based Therapeutics: Critical Drug Delivery and Developability Issues. Journal of pharmaceutical sciences, 105(2), 406-416. https://doi.org/10.1016/j.xphs.2015.10.018

Kolupaev, Yu. E., Karpets, Yu. V., Beschasniy, S. P., & Dmitriev, A. P. (2019). Gasotransmitters and their role in adaptive reactions of plant cells. Cytology and Genetics. 53, 392-406. https://doi.org/10.3103/S0095452719050098

Rose, J. J., Wang, L., Xu, Q., McTiernan, C. F., Shiva, S., Tejero, J., & Gladwin, M. T. (2017). Carbon Monoxide Poisoning: Pathogenesis, Management, and Future Directions of Therapy. American journal of respiratory and critical care medicine, 195(5), 596-606. https://doi.org/10.1164/rccm.201606-1275CI

Olas, B. (2014). Carbon monoxide is not always a poison gas for human organism: Physiological and pharmacological features of CO. Chemico-biological interactions, 222, 37-43. https://doi.org/10.1016/j.cbi.2014.08.005

Beschasnyi, S., & Hasiuk, O. (2020). CO-Releasing Molecule (CORM-2) in the Regulation of Ca2+-Dependent K+-Permeability of Erythrocyte. Ukrainian Journal of Medicine, Biology and Sport, 5(2), 166-171. https://doi.org/10.26693/jmbs05.02.166

Park, J., Joe, Y., Ryter, S. W., Surh, Y. J., & Chung, H. T. (2019). Similarities and Distinctions in the Effects of Metformin and Carbon Monoxide in Immunometabolism. Molecules and cells, 42(4), 292-300. https://doi.org/10.14348/molcells.2019.0016

Motterlini, R., & Foresti, R. (2017). Biological signaling by carbon monoxide and carbon monoxide-releasing molecules. American journal of physiology. Cell physiology, 312(3), C302-C313. https://doi.org/10.1152/ajpcell.00360.2016

Ryter, S. W., & Choi, A. M. (2016). Targeting heme oxygenase-1 and carbon monoxide for therapeutic modulation of inflammation. Translational research : the journal of laboratory and clinical medicine, 167(1), 7-34. https://doi.org/10.1016/j.trsl.2015.06.011

Adach, W., & Olas, B. (2017). The role of CORM-2 as a modulator of oxidative stress and hemostatic parameters of human plasma in vitro. PloS one, 12(9), e0184787. https://doi.org/10.1371/journal.pone.0184787

Magierowski, M., Magierowska, K., Hubalewska-Mazgaj, M., Sliwowski, Z., Ginter, G., Pajdo, R., Chmura, A., Kwiecien, S., & Brzozowski, T. (2017). Carbon monoxide released from its pharmacological donor, tricarbonyldichlororuthenium (II) dimer, accelerates the healing of pre-existing gastric ulcers. British journal of pharmacology, 174(20), 3654-3668. https://doi.org/10.1111/bph.13968

Tashireva, L. A., Starikova, E. G., Novickij, V. V., & Rjazanceva, N. V. (2012). Vnutrikletochnye misheni proapoptoticheskogo vlijanija gazovyh transmitterov [Intracellular targets of proapoptotic influence of gaseous transmitters]. Annals of the Russian academy of medical sciences, 67(10), 77-81. [in Russian]. https://doi.org/10.15690/vramn.v67i10.420

Starikova, Ye. G. (2012). Antiproliferativnyi potentsial monooksida ugleroda [Antiproliferative potential of carbon monoxide]. Bulletin of Siberian Medicine, 11(4), 68-71. [in Russian]. https://doi.org/10.20538/1682-0363-2012-4-68-71

Mahan V. L. (2020). Cardiac function dependence on carbon monoxide. Medical gas research, 10(1), 37-46. https://doi.org/10.4103/2045-9912.279982

Downloads

How to Cite

1.
Beschasnyi SP, Hasiuk OM. The donor of carbon monoxide (CORM-2) affects the level of serum immunoglobulins and the state of the bone marrow during the immune response in mice. Current issues in pharmacy and medicine: science and practice [Internet]. 2020Nov.16 [cited 2024Oct.6];13(3). Available from: http://pharmed.zsmu.edu.ua/article/view/216229

Issue

Section

Original research