Investigation of the irritant effects and allergenic properties of the Iron(IV) clathrochelate complexes
During the preclinical studies of new drugs, the study of the degree of manifestation of their irritant and allergenic effects affects subsequent clinical studies, for example the routes of administration, the need to add excipients to reduce irritation. The article presents the results of studies of the irritant effects and allergenic properties of the Iron in rare unconventional valence – IV. The irritant effect of the Iron(IV) clathrochelate complexes on the skin was studied comprehensively. 20 rabbits were divided into 4 groups (control and three experimental), 5 animals each. The ointment on the vaseline and aqueous solution of the Iron(IV) clathrochelate complexes was applied to the skin of rabbits of the experimental groups. Also this solution was introduced subcutaneously. The investigated dosage forms were used at a dose of 1 ml/kg body weight (based on the active ingredient 500 mg/kg body weight of the laboratory animal). The results of the studies showed that of the Iron(IV) clathrochelate complexes has no irritant properties when used externally and is characterized by a lack of local reaction by subcutaneous injection. Determination of allergenic properties was performed by detecting itching and swelling in the guinea pigs in animals which were sensitized with this substance. In addition, in order to assess the severity of the inflammatory reaction, the skin temperature was determined before the experiment and on the 20th day of the experiment, and the skin fold thickness was measured using a caliper. The results of the studies showed that there is no allergic action of the Iron(IV) clathrochelate complexes. The results of the ophthalmic test on laboratory animals confirmed the data obtained.Therefore, comprehensive studies of the irritant and allergenic effects of the Iron(IV) clathrochelate complexes were performed for the first time. The Iron(IV) clathrochelate complexes in the form of ointment and solution does not irritate the skin and mucous membranes and has no allergenic properties to the body of the laboratory animals.
Bonkovsky, S., & Herbert, L. (1991). Iron and the Liver. The American journal of the medical sciences, 301(1), 32–43. doi: 10.1097/00000441-199101000-00006.
Commission of the European Communities: Council Directive of 18 December 1986 on the Lows, regulat-ing the Application of Principles of Good Laboratory Practice and the Verification of Their Applications for Tests on Chemical Substances (87/18/EEC) (1991). The Rules Governing Medicinal Products in the Euro-pean Community, 1, 145–146.
Derkach, I. (2017). Suchasni tendencii na vitchyznjano-mu rynku ferumvmisnyh preparativ dlja tvaryn [Modern trends of the Ukrainian market of ferumcontaining products for animals]. Naukovyj visnyk Lvivskogo nacionalnogo universytetu vet-erynarnoi medycyny ta biotehnologij imeni S. Z. Gzhyckogo, 19(78), 23–25. doi: 10.15421/nvlvet7805 (in Ukrainian).
Dukhnitsky, V. B., Derkach, I. M., Derkach, S. S., Plutenko, M. O. & Fritsky, I. O. (2019). Influence of iron (IV) clathrochelate complex on quail blood parameters and weight characteristics. Ukrainian Journal of Ecology, 9(3), 126–131. doi: 10.15421/2019_719.
Dukhnitsky, V. B., Derkach, I. M., Plutenko, M. O., Fritsky, I. O., & Derkach, S. S. (2018). Vyznachennja parametriv gostroi toksychnosti ferumu (IV) na bilyh myshah [Determination of the accumulative toxicity parameters of iron (IV) on white mice]. Ukrainian Journal of Ecology, 8 (2), 308–312. doi: 10.15421/2018_343 (in Ukrainian).
Dukhnitsky, V. B., Derkach, I. M., Plutenko, M. O., Fritsky, I. O., & Derkach, S. S. (2019). Cumulative properties of Iron(IV) clathrochelate in rats [Kumu-liatyvni vlastvosti klatrokhelatu Ferumu (IV) dlia bilykh shchuriv]. Visnyk PDAA, 2, 238–246 (in Ukrainian).
Dukhnitsky, V. B., Kalachniuk, L. H., Derkach, I. M., Derkach, S. S., Plutenko, M. O. & Fritsky, I. O. (2020). Iron(IV) hexahydrazide clathrochelate complexes: the chronic toxicity study. Ukrainian Journal of Ecol-ogy, 9(3), 18–23. doi: 10.15421/2020_3.
Dukhnitsky, V., Derkach, I., Derkach, S., Fritsky, I., & Plutenko, M. (2019). Chronic toxicity of the Iron (IV) clathrochelate complexes for white rats [Khronichna toksychnist klatrokhelatu Ferumu (IV) dlia bilykh shchuriv]. Scientific Messenger of LNU of Veterinary Medicine and Biotechnologies. Series: Veterinary Sciences, 21(95), 15–21. doi: 10.32718/nvlvet9503 (in Ukrainian).
Dukhnitsky, V., Derkach, I., Plutenko, M., Fritsky, I., & Derkach, S. (2019). Acute toxicity of the iron clathrochelate complexes. Regulatory Mechanisms in Biosystems, 10(3), 276–279. doi: 10.15421/021942.
Evans, J. L., & Abraham, P. A. (1973). Anemia, Iron Storage and Ceruloplasmin in Copper Nutrition in the Growing Rat. The Journal of Nutrition, 103(2, 1), 196–201. doi: 10.1093/jn/103.2.196.
Ganz, T. (2013). Systemic iron homeostasis. Physiological Reviews, 93(4), 1721−1741. doi: 10.1152/physrev.00008.
Jiefen, C., Yinping, L., Peng, Y., Qiping, Zh., Jingfeng, W., Yongzhou, Ch., & Peng, W. (2017). A novel low molecular weight Enteromorpha polysaccharide-iron (III) complex and its effect on rats with iron deficiency anemia (IDA). International journal of biological macromolecules, 108, 412–418. doi: 10.1016/j.ijbiomac.2017.12.033.
Karput', I. M., & Nikoladze, M. G. (2003). Diagnostika i profilaktika alimentarnoj anemii porosjat. Veterinarija, 4, 34–37 (in Russian).
Killip, S., & Bennett, M. (2008). Iron Deficiency Anemia. American Family Physician., 78(8), 671–678. https://www.aafp.org/afp/2013/0115/p98.html.
Kim, J. C., Wilcock, P., & Bedford, M. R. (2018). Iron status of piglets and impact of phytase superdosing on iron physiology: A review. Animal Feed Science and Technology, 235, 8–14.
Kocjumbas, I. Ja. (2006). Doklinichni doslidzhennja vet-erynarnyh likars'kyh zasobiv. L'viv. Triada pljus (in Ukrainian).
Toksykolohichnyi kontrol novykh zasobiv zakhystu tvaryn (Metodychni rekomendatsii) (1996). Holovnym upravlinniam veterynarnoi medytsyny Min. Silhospprodu Ukrainy. Kyiv, 33 (in Ukrainian).
Tomyn, S., Shylin, S. I., Bykov, D., Ksenofontov, V., Gumienna-Kontecka, E., Bon, V., & Fritsky, I. O. (2017). Indefinitely stable iron (IV) cage complexes formed in water by air oxidation. Nature Communications, 8, 1−8.
Walter, T., Olivares, M., Pizarro, F., & Muñoz, C. (1997). Iron, Anemia, and Infection. Nutrition Reviews, 55(4), 111–124. doi: 10.1111/j.1753-4887.1997.tb06462.x.
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