Determination of toxicological characteristics of a complex antiemeric drug based on maduramycin and nicarbazine

Authors

DOI:

https://doi.org/10.15587/2519-8025.2021.235941

Keywords:

toxicity, mice, rats, guinea pigs, maduramycin, nicarbazine, eimeriosis

Abstract

The aim: to determine the parameters of acute toxicity of the preparative form of an antiemeric agent based on maduramycin and nicarbazine for white mice, white rats and guinea pigs with a single oral administration.

Materials and methods. Determination of acute toxicity of the formulation by oral administration was performed on 48 adult male mice, 48 adult nonlinear male rats, 48 adult male guinea pigs. To conduct an experiment on the principle analogues were formed seven experimental and one control group, 6 animal each. The dose of the formulation was calculated individually based on body weight values. It should be noted that the total volume of the emulsion of the formulation administered orally is not exceeded 1.0 cm3per 100 gram b. w.

Results. Toxicometric parameters of the formulation were calculated by the method of least squares for probit analysis of mortality curves. It was found that the LD50 of the preparative form of antiemeric agent for white mice for a single oral administration is 238.05±28.08 mg/kg, LD16 – 128.71 mg/kg, LD84 – 347.39 mg/kg, LD100 - 402, 06 mg/kg body weight, respectively.

LD50 of the preparative form of antiemeric agent for white rats with a single oral administration is 260.51±28.83 mg/kg, LD16 – 148.39 mg/kg, LD84 – 372.65 mg/kg, LD100 – 428.71 mg/kg body weight, respectively.

LD50 of the preparative form of antiemeric agent for guinea pigs for a single oral administration is 275±21.12 mg/kg, LD16 – 201.74 mg/kg, LD84 – 348.25 mg/kg, LD100 – 384.88 mg/kg body weight body respectively.

Conclusions. According to SOU 85.2-37-736: 2011 "Veterinary drugs. Determination of acute toxicity” preparative form of a complex antiemeric agent based on maduramycin and nicarbazine on the degree of toxicity can be attributed to moderately dangerous substances (3rd hazard class)

Author Biographies

Roman Dotsenko, National University of Pharmacy

PhD, Senior Researcher,

Associate Professor

Department of Veterinary Medicine and Pharmacy

Yevheniia Vashchyk, National University of Pharmacy

Doctor of Veterinary Sciences, Associate Professor

Department of Veterinary Medicine and Pharmacy

Andriy Zakhariev, National University of Pharmacy

PhD, Associate Professor

Department of Veterinary Medicine and Pharmacy

Andrii Zemlianskyi, National University of Pharmacy

PhD, Assistant

Department of Veterinary Medicine and Pharmacy

Ekaterina Dotsenko, National Scientific Center «Institute of Experimental and Clinical Veterinary Medicine»

PhD, Senior Researcher

Laboratory "Veterinary sanitation and parasitology"

Nataliia Seliukova, National University of Pharmacy

Doctor of Biological Sciences, Associate Professor

Department of Veterinary Medicine and Pharmacy

References

  1. Rybicki, M. J. (2020). Coccidiostats in treating coccidiosis. Żywność. Nauka. Technologia. Jakość, 2020, 27 (4 (125)), 127–137
  2. Chapman, H. D., Barta, J. R., Blake, D., Gruber, A., Jenkins, M., Smith, N. C. et. al. (2013). A Selective Review of Advances in Coccidiosis Research. Advances in Parasitology, 93–171. doi: http://doi.org/10.1016/b978-0-12-407705-8.00002-1
  3. Noack, S., Chapman, H. D., Selzer, P. M. (2019). Anticoccidial drugs of the livestock industry. Parasitology Research, 118 (7), 2009–2026. doi: http://doi.org/10.1007/s00436-019-06343-5
  4. Dorne, J. L. C. M., Fernández-Cruz, M. L., Bertelsen, U., Renshaw, D. W., Peltonen, K., Anadon, A. et. al. (2013). Risk assessment of coccidostatics during feed cross-contamination: Animal and human health aspects. Toxicology and Applied Pharmacology, 270 (3), 196–208. doi: http://doi.org/10.1016/j.taap.2010.12.014
  5. Radičević, T., Janković, S., Stefanović, S., Nikolić, D., Đinović-Stojanović, J., Spirić, D. (2017). Coccidiostats in unmedicated feedingstuffs for poultry. IOP Conference Series: Earth and Environmental Science, 85, 012080. doi: http://doi.org/10.1088/1755-1315/85/1/012080
  6. National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 196129, Maduramicin. from https://pubchem.ncbi.nlm.nih.gov/compound/Maduramicin Last accessed: 21.06.2021
  7. Chen, X., Zhang, Y., Jiang, S., Huang, S. (2019). Maduramicin induces apoptosis through ROS-PP5-JNK pathway in skeletal myoblast cells and muscle tissue. Toxicology, 424, 152239. doi: http://doi.org/10.1016/j.tox.2019.152239
  8. Gao, X., Song, X., Zuo, R., Yang, D., Ji, C., Ji, H. et. al. (2020). Ionophore Toxin Maduramicin Produces Haff Disease-Like Rhabdomyolysis in a Mouse Model. International Journal of Environmental Research and Public Health, 17 (21), 7882. doi: http://doi.org/10.3390/ijerph17217882
  9. National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 9507, Nicarbazin. https://pubchem.ncbi.nlm.nih.gov/compound/Nicarbazin Last accessed: 21.06.2021
  10. Filazi, A., Yurdakok-Dikmen, B.; Gupta, R., Srivastava, A., Lall, R. (Eds.) (2019). Regulatory Guidelines for Nutraceuticals and Dietary Supplements for Animals in Turkey. Nutraceuticals in Veterinary Medicine. Cham: Springer, 829–836. doi: http://doi.org/10.1007/978-3-030-04624-8_62
  11. OECD (1987). Test No. 401: Acute Oral Toxicity. OECD Guidelines for the Testing of Chemicals, Section 4. Paris: OECD Publishing. doi: http://doi.org/10.1787/9789264040113-en
  12. Prozorovskii, V. B. (2007). Statisticheskaia obrabotka rezul'tatov farmakologicheskih issledovanii. PFBN, 3-4.
  13. Pro zahist tvarin vіd zhorstokogo povodzhennia (2021). Zakon Ukraini No. 3447-IV. 21.02.2006. Available at: http://zakon5.rada.gov.ua/laws/show/3447-15
  14. SOU 85.2-37-736: 2011 "Veterinary drugs. Determination of acute toxicity" (2011). Kyiv: Ministry of Agrarian Policy, 16.
  15. Arisov, M. V., Urazaev, D. N., Kachanova, E. O., Pavlova, A. S. (2020). General principles of conducting preclinical toxicology studies of antiparasitic drugs for veterinary use. IOP Conference Series: Earth and Environmental Science, 548, 042042. doi: http://doi.org/10.1088/1755-1315/548/4/042042
  16. Sharma, N. (2005). Toxicity of maduramicin. Emergency Medicine Journal, 22 (12), 880–882. doi: http://doi.org/10.1136/emj.2004.020883
  17. Rumbeiha, W. K., Snider, D. B. (2014). Veterinary Toxicology. Encyclopedia of Toxicology. Academic Press, 915–928. doi: https://doi.org/10.1016/B978-0-12-386454-3.00444-9
  18. Kociumbas, І. Ia. (2005). Doklіnіchnі doslіdzhennia veterinarnih lіkars'kih zasobіv. Lvіv: Trіada plius, 134–147.
  19. Shlosberg, A., Perl, S., Harmelin, A., Hanji, V., Bellaiche, M., Bogin, E. et. al. (1997). Acute maduramicin toxicity in calves. Veterinary Record, 140 (25), 643–646. doi: http://doi.org/10.1136/vr.140.25.643

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Published

2021-06-30

How to Cite

Dotsenko, R., Vashchyk, Y., Zakhariev, A., Zemlianskyi, A., Dotsenko, E., & Seliukova, N. (2021). Determination of toxicological characteristics of a complex antiemeric drug based on maduramycin and nicarbazine. ScienceRise: Biological Science, (2(27), 37–43. https://doi.org/10.15587/2519-8025.2021.235941

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Section

Veterinary research