Study of acute and subacute toxicity parameters of “Rybokhin” biological product on the model of carp

  • A. V. Yevtushenko National Scientific Center “Institute of Experimental and Clinical Veterinary Medicine”, Kharkov, Ukraine
  • O. S. Sirenko National Scientific Center “Institute of Experimental and Clinical Veterinary Medicine”, Kharkov, Ukraine
  • V. S. Boyko National Scientific Center “Institute of Experimental and Clinical Veterinary Medicine”, Kharkov, Ukraine
  • M. E. Romanko National Scientific Center “Institute of Experimental and Clinical Veterinary Medicine”, Kharkov, Ukraine
Keywords: chloroquine, fish, lethal dose, acute toxicity, submerged toxicity, blood, clinical and biochemical indica-tors


The goal of the work was to study of acute and subacute toxicity parameters of Rybokhin biological product (AI – chloroquine refer to derivatives 4-aminohinolines) on the model of carp. This drug is effective in the treatment of diseases caused by parasitic Protozoa and Monogenea. Carp scales of two years old were used in experiments. To determine acute toxicity, the fish were prescribed with chloroquine (by AI) in doses of 100; 200; 300; 400; 500; 600; 800; 1000 mg/kg of live weight. Two experimental and control fish groups of 30 individuals each were formed to determine subacute toxicity of Rybokhin. Experimental groups of fish were prescribed with “Rybokhin in a dose (by AI) of 50 mg/kg and 10 mg/kg for two consecutive days. Blood samples were collected from six fish species from each group for clinical and biochemical indicators after 48 hours, 7, 14, 21 and 28 days. The hemoglobin content, number of red blood cells and leukocytes blood were determined. The intensity of peroxide oxidation of lipids (PОL), catalase activity, level of total antioxidant capacity (TAC), total proteins, albumin, globulins and glucose, circulating immune complexes (CІC) and seromucoids concentration, level of enzymatic activity: aspartate transaminase (АSТ), alanine transaminase (АLТ), ά-amylase blood plasma were determined. According to the research results, indicators of acute toxicity for carp were determined, namely LD50of chloroquine is 528.66 ± 68.01 mg/kg; LD16 – 224.512 mg/kg; LD84 – 832.81 mg/kg; LD100 – 984.89 mg/kg, which indicate that the drug is low-toxic to fish (belongs to the fourth group of toxicity). When administrating of 50.0 mg/kg of “Rybokhin” (by AI) twice a day, the most expressed metabolic changes in fish body were observed on 21 day after its last administration. Thus, the drug’s toxic impact is in proteinogram alteration, transamination processes and in decreasing of fish immune reactivity. It points to the prevalence of catalytic processes over anabolic. Metabolic alterations are obviously directed to the activation of detoxication processes with increased energy use in fish body after getting of higher dosage of the product. So, on 28 day of experiment, the major part of studied parameters retrieved to control level. It was found that when the product was administrated twice a day in the dosage 10.0 mg/kg (by AI), which is used for treatment of parasitic diseases, no reliable changes of clinical and biochemical indices were detected in fish blood during the experiment.


Download data is not yet available.


Al-Akel, A.S., Alkahem-Al-Balawi, H.F., Al-Misned, F., Mahboob, S., Ahmad, Z., & Suliman, E.M. (2010). Ef-fects of dietary copper exposure on accumulation, growth, and hematological parameters in Cyprinus carpio. Toxicological and Environmental Chemistry, 92, 1865–1878. doi: 10.1080/02772248.2010.486230.

Bono, D.P. (1994). Free radicals and antioxidants in vas-cular biology: the roles of reaction kinetics, environ-ment and substrate turnover. QJM, 87(8), 445–453. doi: 10.1093/oxfordjournals.qjmed.a068954.

Demidov, N.V., & Berezkina, S.V. (1986). Metodicheskie rekomendacii po ocenke angel'mintikov v veterinarii. M.: VASHNIL (in Russian).

Dirksen, G., Gründer, H. D., Stöber, M. (1990). Die klinische Untersuchung des Rindes. Berlin; Hamburg: Paul Parey, 367–385.

European convention for the protection of vertebrate animals used for experimental and other scientific purposes. Council Directive 86/609/EEC of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes. Offical Journal of the European Communities L. 358. 1986. 1–29.

Gavrilov, V.B., & Mishkorudnaja, M.I. (1983). Spektro-fotometricheskoe opredelenie soderzhanija gidrope-rekisej lipidov v plazme krovi. Lab. delo, 3, 33–36 (in Russian).

Gutyj, B., Martyshchuk, T., Bushueva, I., Semeniv, B., Parchenko, V., Kaplaushenko, A., Magrelo, N., Hirkovyy, A., Musiy, L., & Murska, S. (2017). Mor-phological and biochemical indicators of blood of rats poisoned by carbon tetrachloride and subject to ac-tion of liposomal preparation. Regulatory Mecha-nisms in Biosystems, 8(2), 304–309. doi: 10.15421/021748.

Hazanov, A.I. (1988). Funkcional'naja diagnostika boleznej pecheni. 2 e izd., pererab. i dop. M. : Medicina (in Russian).

Hemdal, J.F. (2013). Aquarium Fish: Chloroquine: A “New” Drug for Treating Fish Diseases.

Khariv, M., Gutyj, B., Ohorodnyk, N., Vishchur, O., Khariv, I., Solovodzinska, I., Mudrak, D., Grymak, C., & Bodnar, P. (2017). Activity of the T- and B-system of the cell immunity of animals under conditions of oxidation stress and effects of the liposomal drug. Ukrainian Journal of Ecology, 7(4), 536–541. doi: 10.15421/2017_157.

Klebanov, G.I. (1988). Ocenka antiokislitel'noj aktivnosti plazmy krovi s primeneniem zheltochnyh lipoprotei-dov. Lab. delo, 5, 59–62 (in Russian).

Kondrahin, I.P. (1985). Klinicheskaja laboratornaja diag-nostika v veterinarii. M.: Agropromizdat (in Russian).

Koroljuk, M.A. (1988). Opredelenie aktivnosti katalaz. Lab. Delo, 1, 16–18 (in Russian).

Kotsiumbas, I.Ia. (2006). Doklinichni doslidzhennia veterynarnykh likarskykh zasobiv. Lviv (in Ukrainian).

Krafts, K., Hempelmann, E., & Skórska-Stania, A. (2012). From methylene blue to chloroquine: a brief review of the development of an antimalarial therapy. Parasitology Research, 111(1), 1–6. doi: 10.1007/s00436-012-2886-x.

Men'shikov, V.V. (1987). Laboratornye metodicheskie issledovanija v klinike. M.: Medicina (in Russian).

Prozorovskij, V.B. (2007). Statisticheskaja obrabotka rezul'tatov farmakologicheskih issledovanij. Psi-hofarmakologija i biol. narkologija, 7(3–4), 2090–2120 (in Russian).

Todoriuk, V.B., Hunchak, V.M., Gutyj, B.V., Gufriy, D.F., Hariv, I.I., Khomyk, R.I. , & Vasiv, R.O. (2018). Pre-clinical research of the experimental preparation “Ferosel T”. Ukrainian Journal of Veterinary and Ag-ricultural Sciences, 1(1), 3–9. doi: 10.32718/ujvas1-1.01.

Vaziri, A., & Warburton, B. (1994). Slow release of chlo-roquine phosphate from multiple taste-masked W/O/W multiple emulsions. Journal

of Microencapsulation, 11(6), 641–648. doi: 10.3109/02652049409051114.

Vlizlo, V.V. (2012). Laboratorni metody doslidzhen u biolohii, tvarynnytstvi ta veterynarnii medytsyni: dovid. Lviv: Spolom (in Ukrainian).

Abstract views: 31
PDF Downloads: 11
How to Cite
Yevtushenko, A., Sirenko, O., Boyko, V., & Romanko, M. (2019). Study of acute and subacute toxicity parameters of “Rybokhin” biological product on the model of carp. Scientific Messenger of LNU of Veterinary Medicine and Biotechnologies. Series: Veterinary Sciences, 21(94), 25-32.