Original Scientific Article
Study of mutagenic and antitoxic properties of gentabiferon-B
Sergey Shabunin
,
Vasilina Gritsyuk
,
Galina Vostroilova
,
Dmitriy Shabanov
,
Nina Khokhlova
*
,
Anastasiya Korchagina
Received: 15 September 2021
Received in revised form: 08 February 2022
Accepted: 09 February 2022
Available Online First: 02 March 2022
Published on: 15 March 2022
Correspondence: Nina Khokhlova, nina_xoxlova@mail.ru
Abstract
The combination of immunomodulators and antibiotics in the treatment of animals with diseases of bacterial etiology is one of the effective strategies for animal therapy. The drug gentabiferon-B combines antibiotic gentamicin and speciesspecific (bovine) recombinant interferons -α and -γ. The study aimed to evaluate the effect of course application of gentabiferon-B on the cytogenetic stability of bone marrow cells of outbred mice after administering mitomycin C (MMC). The proportion of polychromatophilic erythrocytes in the bone marrow was assessed. There was no effect of gentabiferon-B on the frequency of polychromatophilic erythrocytes with micronuclei in both healthy animals and mice with MMC-induced cytogenetic instability. The course application of gentabiferon-B before the administration of MMC led to an increase in the proportion of polychromatophilic erythrocytes (46.03±2.61%) which was non-significantly different than the negative control group. The administration of MMC alone caused a decrease in the proportion of polychromatophilic erythrocytes to 33.33±1.83%. The antitoxic effect of gentabiferon-B led to an increase in the level of polychromatophilic erythrocytes by 38.1% compared to the group that received only MMC. Studies have shown that gentabiferon-B does not have mutagenic activity and anticlastogenic properties, however, it reduces the toxic effect of MMC. In conclusion, it is indicative that gentabiferon-B has antitoxic properties and can be safely used in animal therapy.
Keywords: gentabiferon-B, micronucleus test, mitomycin, mutagenicity
References
- Miroshnikova, M.S. (2021). Study of the potentiated effect of antimicrobial drugs against probiotic strains of microorganisms. Izvestia Orenburg State Agrarian University 2(88): 168-173. [in Russian] https://doi.org/10.37670/2073-0853-2021-88-2-168-173
- Vostroilova, G.A., Shakhov, A.G., Shabunin, S.V., Sashnina, L.Yu., Parshin, P.A., Cheskidova, L.V., Kantorovich, Yu.A. (2018). Сorrective influence of hentabiferon-С on the immune status of postweaned piglets snd its rffectiveness in the prevention of intestinal infections. Russ Agric Sci. 6, 58-61.
- Cheskidova, L.V., Briukhova, I.V., Grigoreva, N.A. (2019). Advanced research directions of creation of new generation medicines for animals with application of biotechnologies (Review). Bulletin Vet Pharmacol. 2(7): 29-38. [in Russian] https://doi.org/10.17238/issn2541-8203.2019.2.29
- Mironov, A.N., Bunatyan, N.D., Vasil’ev, A.N., Verstakova, O.L., Zhuravleva, M.V., Lepahin, V.K., Korobov, N.V., et al. (2012). Guidelines for conducting preclinical studies of drugs. Part one. p. 944. Moscow, Russia: Grief and K
- Engalycheva, G.N., Syubaev, R.D., Goryachev, D.V. (2019). Quality standards of preclinical pharmacological studies. The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products 9(4): 248-255. https://doi.org/10.30895/1991-2919-2019-9-4-248-255
- Parlakpinar, H., Tasdemir, S., Polat, A., Bay-Karabulut, A., Vardi, N., Ucar, M., Yanilmaz, M., Kavakli, A., Acet, A. (2006). Protective effect of chelerythrine on gentamicin-induced nephrotoxicity. Cell Biochem Funct. 24(1):41-48. https://doi.org/10.1002/cbf.1182 PMid:15584091
- Gozhenko, A.I., Vladimirova, M.P., Topor, E.A. (2005). Renal dysfunctions in white rats after a single administration of gentamicin. Nephrology. 9(4): 75-79. [in Russian]
- Hosaka, E.M., Santos, O.F.P., Seguro, A.C., Vattimo, M.F.F. (2004). Effect of cyclooxygenase inhibitors on gentamicin induced nephrotoxicity in rats. Braz J Med Biol Res. 37(7): 979-985. https://doi.org/10.1590/S0100-879X2004000700006 PMid: 15264004
- Durnev, A.D. (2018). Antimutagenesis and antimutagens. Hum Physiol. 44(3): 116-137. [in Russian] https://doi.org/10.1134/S0362119718030052
- Horisberger, M.A., de Staritzky, K. (1987). A recombinant human interferon-alpha B/D hybrid with a broad host-range. J Gen Virol. 68(Pt 3): 945- 948. https://doi.org/10.1099/0022-1317-68-3-945 PMid:3029315
- Martal, J.L., Chêne, N.M., Huynh, L.P., L’Haridon, R.M., Reinaud, P.B., Guillomot, M.W., Charlier, M.A., Charpigny, S.Y. (1998). IFN-tau: a novel subtype I IFN1. Structural characteristics, non-ubiquitous expression, structure-function relationships, a pregnancy hormonal embryonic signal and crossspecies therapeutic potentialities. Biochimie 80(8- 9): 755-777. https://doi.org/10.1016/S0300-9084(99)80029-7
- Blankenstein, T., Qin, Z. (2003). The role of IFNgamma in tumor transplantation immunity and inhibition of chemical carcinogenesis. Curr Opin Immunol. 15(2): 148-154. https://doi.org/10.1016/S0952-7915(03)00007-4
- Makedonov, G.P., Chekova, V.V., Yakubovskaya, E.L., Zasukhina, G.D. (1990). Modification of DNA repair by human interferons. Acta Biol Hung. 41(1- 3): 187-197.
- Kumari, S., Naik, P., Vishma, B.L., Salian, S.R., Devkar, R.A., Khan, S., Mutalik, S., Kalthur, G., Adiga, S.K. (2016). Mitigating effect of Indian propolis against mitomycin C induced bone marrow toxicity. Cytotechnology 68(5): 1789-1800. https://doi.org/10.1007/s10616-015-9931-4 PMid:26590833 PMCid:PMC5023552
- Sinitsky, M.Y., Kutikhin, A.G., Tsepokina, A.V., Shishkova, D.K., Asanov, M.A., Yuzhalin, A.E., Minina, V.I., Ponasenko, A.V. (2020). Mitomycin C induced genotoxic stress in endothelial cells is associated with differential expression of proinflammatory cytokines. Mutat Res Genet Toxicol Environ Mutagen. 858-860: 503252. https://doi.org/10.1016/j.mrgentox.2020.503252 PMid:33198933
- Hayashi, M. (2016). The micronucleus test-most widely used in vivo genotoxicity test. Genes Environ. 38, 18. https://doi.org/10.1186/s41021-016-0044-x PMid:27733885 PMCid:PMC5045625
- Agarwal, D.K., Chauhan, L.K. (1993). An improved chemical substitute for fetal calf serum for the micronucleus test. Biotech Histochem. 68(4): 187-188. https://doi.org/10.3109/10520299309104695 PMid:8218570
- The European agency for the evaluation of medicinal products, veterinary medicines and inspections (2001). Committee for veterinary medicinal products. Gentamicin summary report. EMEA/ MRL/803/01-FINAL. November 2001. 1-9. https://www.ema.europa.eu/en/documents/mrl-report/gentamicin-summary-report-3-committee-veterinary-medicinal-products_en.pdf
- El-Ashmawy, I.M., El-Nahas, A.F., Salama, O.M. (2006). Grape seed extract prevents gentamicininduced nephrotoxicity and genotoxicity in bone marrow cells of mice. Basic Clin Pharmacol Toxicol. 99(3): 230-236. https://doi.org/10.1111/j.1742-7843.2006.pto_497.x PMid:16930296
- Velasco-Velázquez, M.A., Maldonado, P.D., Barrera, D., Torres, V., Zentella-Dehesa, A., Pedraza-Chaverrí, J. (2006). Aged garlic extract induces proliferation and ameliorates gentamicin-induced toxicity in LLC-PK1 cells. Phytother Res. 20(1): 76-78. https://doi.org/10.1002/ptr.1780 PMid:16397848
- Martínez-Salgado, C., Eleno, N., Tavares, P., Rodríguez-Barbero, A., García-Criado, J., Bolaños, J.P., López-Novoa, J.M. (2002). Involvement of reactive oxygen species on gentamicin-induced mesangial cell activation. Kidney Int. 62(5): 1682-1692. https://doi.org/10.1046/j.1523-1755.2002.00635.x PMid:12371968
- Bustos, P.S., Deza-Ponzio, R., Páez, P.L., Albesa, I., Cabrera, J.L., Virgolini, M.B., Ortega, M.G. (2016). Protective effect of quercetin in gentamicin-induced oxidative stress in vitro and in vivo in blood cells. Effect on gentamicin antimicrobial activity. Environ Toxicol Pharmacol. 48, 253-264. https://doi.org/10.1016/j.etap.2016.11.004 PMid:27846408
- Kim, J., Lee, Y., Koh, W.S., Kim, C., Choi, I.Y., Kwon, S.C., Lee, G.S., Han, J.Y., Lee, M. (2007). Genotoxicity assessment of HM10620 containing recombinant human interferon-alpha. Drug Chem Toxicol. 30(1): 83-95. https://doi.org/10.1080/01480540601017744 PMid:17364866
- Bidgoli, S.A., Heshmati, M., Keyhan, H., Afshary, A. (2012). Genotoxicity assessment of ecombinant human interferon gamma in human lymphocytes. JAASP 1(2):107-115.
- Tsoncheva, V.L., Todorova, K.A., Ivanov I.G., Maximova, V.A. (2008). Influence of interferons on the repair of UV-damaged DNA. Z Naturforsch C J Biosci. 63(3-4): 303-307. https://doi.org/10.1515/znc-2008-3-423 PMid:18533478
- Hara, T., Koyama, K., Miyazaki, H., Ohguro, Y., Shimizu, M. (1977). Safety evaluation of KW-1062. I. Acute toxicity in mice, rats and dogs, subacute and chronic toxicity in rats (author’s transl). Jpn J Antibiot. 30(6): 386-407.
- Steinbach, T.J., Patrick, D.J., Cosenza, M.E. (2019). Toxicologic pathology for non-pathologists. New York: Springer; Humana https://doi.org/10.1007/978-1-4939-9777-0
- Haitov, R.M., Ataullahanov, R.I., Allenov, S.N., Alyaev, Y.U.G., Balabolkin, I.I., Batkaev, E.A., Batkaeva, N.V., et al. (2014). Immunotherapy: a guide for physicians. Moskow: GEOTAR-Media [in Russian]
- Selleri, C., Sato, T., Anderson, S., Young, N.S., Maciejewski, J.P. (1995). Interferon-gamma and tumor necrosis factor-alpha suppress both early and late stages of hematopoiesis and induce programmed cell death. J Cell Physiol. 165(3): 538-546. https://doi.org/10.1002/jcp.1041650312 PMid:7593233
- Lin, F., Karwan, M., Saleh, B., Hodge, D.L., Chan, T., Boelte, K.C., Keller, J.R., Young, H.A. (2014). IFN-γ causes aplastic anemia by altering hematopoietic stem/progenitor cell composition and disrupting lineage differentiation. Blood 124(25): 3699-3708. https://doi.org/10.1182/blood-2014-01-549527 PMid:25342713 PMCid:PMC4263980
- Schroder, K., Hertzog, P.J., Ravasi, T., Hume, D.A. (2004). Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol. 75(2): 163-189. https://doi.org/10.1189/jlb.0603252 PMid:14525967
- Murayama, T., Takahashi, N., Ikoma, N. (1996). Cytotoxicity and characteristics of mitomycin C. Ophthalmic Res. 28(3): 153-159. https://doi.org/10.1159/000267896 PMid:8829171
- Pawlik, T.M., Keyomarsi, K. (2004). Role of cell cycle in mediating sensitivity to radiotherapy. Int J Radiat Oncol Biol Phys. 59(4): 928-942. https://doi.org/10.1016/j.ijrobp.2004.03.005 PMid:15234026
- Fingert, H.J., Chang, J.D., Pardee, A.B. (1986). Cytotoxic, cell cycle, and chromosomal effects of methylxanthines in human tumor cells treated with alkylating agents. Cancer Res. 46(5): 2463-2467.
- Wang, X.Y., Crowston, J.G., Zoellner, H., Healey, P.R. (2007). Interferon-alpha and interferon-gamma sensitize human tenon fibroblasts to mitomycin-C. Invest Ophthalmol Vis Sci. 48(8): 3655-3661. https://doi.org/10.1167/iovs.06-1121 PMid:17652735
Copyright
© 2022 Shabunin S. This is an open-access article published under the terms of the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Conflict of Interest Statement
The authors have declared that no competing interests exist.
Citation Information
Macedonian Veterinary Review. Volume 45, Issue 1, Pages 79-87 e-ISSN 1857-7415, p-ISSN 1409-7621, DOI: 10.2478/macvetrev-2022-0016, 2022