Evaluation of supramolecular complex of fenbendazole effect on embryonic development

The purpose of the research is to study the embryotropic effect of supramolecular complex of fenbendazole (SMСF).
Materials and methods. The experiment to assess the embryotropic properties of SMCF was carried out on 40 white female and 20 male rats in accordance with the Guidelines for the experimental (preclinical) study of new pharmacological substances. Pregnant female rats were divided into 3 experimental and one control groups. SMCF was administered intragastrically on the 1–6 days of embryogenesis (group 1); on the 7–14 days (group 2) and on the 15–19 days (group 3) in three times therapeutic dose – 6,0 mg/kg of active substance. The animals of the control group received saline from the first to the 19th days of pregnancy. Rats were euthanized on the 20th day of pregnancy. The uterus with fetuses was removed after laparotomy, the number of corpora lutea, implantation sites, the number of living, dead and resorbed fetuses were recorded, the weight and diameter of the placenta were determined. The embryos were examined, weighed, the craniocaudal sizes were determined, the levels of total embryonic, preimplantation and postimplantation embryo death were calculated. The fetuses were examined for abnormalities of internal organs and changes in the skeletal system according to the methods of J. G. Wilson (1965) and A. B. Dawson (1926), modified in the department of embryology of the IEM of the USSR Academy of Medical Sciences.
Results and discussion. As a result, SMCF does not induce toxic effects on the fetus: mortality rates, size and weight of embryos were at the level of the control group in a threefold therapeutic dose 6,0 mg/kg at intragastric administration on the 1–6; 7–14 and 15–19 days of pregnancy. SMCF did not cause external and internal malformations.

1. Varlamova A. I., Skira V. N., Arkhipov I. A. Evaluation of vigisox for embryotoxic and teratogenic effects. «Aktual'nyye problemy razvitiya veterinarnoy nauki»: materialy mezhdunarodnoy konferentsii = "Actual problems of the development of veterinary science": materials of the international conference. Samara, 2014; 72-74. (In Russ.)

2. Varlamova A. I. Methodology for application of supramolecular fenbendazole against helminthosis in ruminants. Rossiyskiy parazitologicheskiy zhurnal = Russian Journal of Parasitology. 2021; 15 (4): 57–60. (In Russ.)

3. Grushinskaya V. A. Influence of benacil on the course of pregnancy in sheep. Byulleten' Vsesoyuznogo instituta gel'mintologii = Bulletin of the All-Union Institute of Helminthology. 1983. 33: 574. (In Russ.)

4. Dyban A. P., Baranov V. S., Akimova I. M. Basic methodological approaches to testing the teratogenic activity of chemicals. Arkhiv anatomii, gistologii i embriologii = Archive of Anatomy, Histology and Embryology. 1970; 10: 89–100. (In Russ.)

5. Dyban A. P., Puchkov V. F., Chebotar N. A. et al. Guidelines for the study of the embryotoxic action of pharmacological substances and their effect on reproductive function. Moscow, MZ USSR, 1986; 21. (In Russ.)

6. Guidelines for the preclinical study of the reproductive toxicity of pharmacological agents. Vedomosti Farmakologicheskogo Komiteta = Bulletin of the Pharmacological Committee. 1998; 1: 13–20. (In Russ.)

7. Order of the Ministry of Health of the USSR No. 1179 dated 10.10.1983 «On approval of the norms for the cost of feed for laboratory animals in health care institutions». (In Russ.)

8. Order of the Ministry of Health of the Russian Federation 199n dated 04/01/2016 "On approval of the rules of good laboratory practice". (In Russ.)

9. Ryabova V. A., Lapteva L. A. Embryotoxicological and teratogenic effects of BMC on rat embryos. Byulleten' Vsesoyuznogo instituta gel'mintologii = Bulletin of the All-Union Institute of Helminthology. 1981; 28: 56-60. (In Russ.)

10. Khabriev R. U. Guidelines for the experimental (preclinical) study of new pharmacological substances. Moscow, Medicine, 2005; 832. (In Russ.)

11. Becker W. Assessment of residues after administration of Panacur. Berliner und Munchener tierarztliche Wochenschrift. 1976; 89 (23): 453-456.

12. Delatour P., Richard Y. The embryotoxic and antimitotic properties of a series of benzimidazoles. Therapie. 1976; 31 (4): 505-515.

13. Düwel D. Safety of fenbendazole in animals. Amer. J. Vet. Res. 1976; 36 (3): 104-107.

14. Düwel D. Treatment of helminthiasis in ruminants – a review. Berliner und Munchener tierarztliche Wochenschrift. 1981; 94 (19): 378-382.

15. Krause D., Reinhard H. J., Köhler W., Tiefenbach B. Untersuchungen uber die wirkung des anthelminthikums fenbendazol auf die spermaqualität von besamungsbullen. Dtsch. tierärztl. Wschr. 1975; 82: 231–233.

16. Tiefenbach B. Fenbendazole, a new anthelminthic for the treatment of gastrointesninal nematodes of domestic animals – experiences in field trials. Proceeding’s 3rd International Congress of Parasitology. Munich, 1974; 3: 1398–1399.