Iron(IV) hexahydrazide clathrochelate complexes: the chronic toxicity study

2020 
One of the main tasks in the fight against anemia is to carry out preventive measures, to develop and to introduce new preparations containing iron, to provide the pharmaceutical market with anti-anemic agents. That's why to investigate the chronic toxic effect of Iron(IV) hexahydrazide clathrochelate (new iron-containing drug) in mice was the article's aim. The study of chronic toxic effect of Iron(IV) clathrochelate was performed on 45 white mice (19–25 g) separated into 3 groups: control (I) and two experimental (II and III). Animals of II and III groups were daily fed the water solution of Iron(IV) clathrochelate at a rate of 125.8 and 251.6 mg/kg of body weight, respectively. It was monitored the dynamics of body weight of white mice, relative coefficients of the mass of internal organs, hemoglobin content and morphological parameters of blood, biochemical indices of blood serum on the 10th, 20th and 30th day of the experiment. It was established a decrease of body weight by 16–21% and relative weight indices of internal organs (liver, kidney, heart, and spleen) – by 5– 43% in white mice of II and III experimental groups, respectively. Changes in the morphological composition of the blood showed stimulation of leukocytopoiesis. A significant decrease in creatinine (hypocreatinemia) and uric acid (hypouricemia) was observed, which indicates an increase in the filtration capacity of the renal glomeruli. Complex studies of the effect of Iron(IV) clathrochelate solution (at a dose of 125.8 and 251.6 mg/kg of body weight) did not cause any visible signs of intoxication and death of animals at the first time. Iron(IV) clathrochelate solution (at a dose of 125.8 mg/kg of body weight) is demonstrated more safe effect. Keywords: Toxicity; Clathrochelate; Body weight; Internal organs coefficient; Morphology; Biochemistry; White mice References Aktas, G., Alcelik, A., Yalcin, A., Karacay, S., Kurt, S., Akduman, M., Savli, H. (2014). Treatment of iron deficiency anemia induces weight loss and improves metabolic parameters. Clinical therapy, 165 (2), 87-9. doi: https://doi.org/10.7471/CT.2014.1688 Belous, A. M. & Konnic, A. T. (1991). Fiziologichna rol` zaliza. Kiev. Naukova Dumka [in Ukrainian]. Bonkovsky, S., Herbert, L. (1991). Iron and the liver. American journal medical science, 301 (1), 32–43. https://doi.org/10.1097/00000441-199101000-00006 Commission of the European Communities: Council Directive of 18 December 1986 on the Lows, regulating 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 European Community. 1, 145–146. Cui, J., Li, Y., Yu, P., Zhan, Q., Wang, J., Chi, Y., Wang, P. (2018). A novel low molecular weight Enteromorpha polysaccharide-iron (III) complex and its effect on rats with iron deficiency anemia (IDA). International journal bioogical macromoleculs, 108, 412-418. doi: https://doi.org/10.1016/j.ijbiomac.2017.12.033 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. Ukrainian Journal of Ecology, 8 (2), 308–312. https://doi.org/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. Visnyk PDAA, 2, 2382–46. Derkach, I. (2017). Suchasni tendencii na vitchyznjanomu rynku ferumvmisnyh preparativ dlja tvaryn. Naukovyj visnyk Lvivskogo nacionalnogo universytetu veterynarnoi medycyny ta biotehnologij imeni S. Z. Gzhyckogo, 19 (78), 23–25. https://doi.org/10.15421/nvlvet7805 [in Ukrainian]. England, J. Bigelow, О., Katherine, M., Heuvelen, V., Farquhar, E., Martinho, M., Meier, K., Frisch, J., Munck E., & Que L. (2014). An ultra-stable oxoiron (IV) complex and its blue conjugate base. Chemical Science, 5, 12041–215. doi: https://doi.org/10.1039/C3SC52755G/ Ganz T. (2013). Systemic iron homeostasis. Physiological review, 93 (4), 1721–1741. doi: https://doi.org/10.1152/physrev.00008 Gerasimenko, S.S., Golovach, A. V., Erina, A.M. (2000). Statistics: Textbook. Kyiv. KNEU. 110–3. Goto, M., Suematsu, Y., Nunes, A.C.F., Jing, W., Khazaeli, M., Lau, W.L., Vaziri, N.D. (2019). Ferric citrate attenuates cardiac hypertrophy and fibrosis in a rat model of chronic kidney disease. Iran journal kidney disorges, 13 (2), 98–104. Groves, J. T. (2006). High-valent iron in chemical and biological oxidations. Journal of Inorganic Biochemistry, 100(4), 4344–47. https://doi.org/10.1016/j.jinorgbio.2006.01.012 Rummianceva, A. G., Tokareva, Y. N. (2004). Iron overloading diseases (hemochromatosis). Мoskwa. Medpractica Press. Kaplia, A. A. (2015). The influence of iron ions on ATP-hydrolases activity of cell membranes of rat colon smooth muscle and kidney. Ukrainian biochemical journal, 87 (1), 83–90. PMID: 26036134 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, 81–84. Killip, S., Bennett, M. (2008). Iron deficiency anemia. American family physician, 15, 78 (8), 671–678. Kotsiumbas, I. Ya. (2006) Doklinichni doslidzhennja veterynarnyh likars'kyh zasobiv. L'viv. Triada pljus [in Ukrainian]. Lubianova, I. P. (2010). Modern concepts about the metabolism of iron from the position of the occupational pathologist. Actual problems of transport medicine, 20 (2), 47–57. Maes, D., Steyaert, M., Vanderhaeghe, C., Lopez Rodriguez, A., de Jong, E., Del Pozo Sacristan, R., Vangroenweghe, F., & Dewulf, J. (2011) Comparison of oral versus parenteral iron supplementation on the health and productivity of piglets. Veterinary record. 19, 168–188. doi: https://doi.org/10.1136/vr.c7033 Saito, H. (2014). Metabolism of iron stores. Journal medical science, 76 (3–4), 235–254. Streyl, K., Carlstron, J., Dantos, E., Mendoza, R., Islas, J.A., & Bhushan C. (2015). Field evaluation of the effectiveness of an oral toltrazuril and iron combination (baycox® iron) in maintaining weaning weight by preventing coccidiosis and anaemia in neonatal piglets. Parasitological reserch, 114 (1), 1932–00. doi: https://doi.org/10.1007/s00436-015-45254–529. Todoriuk, V. B., Hunchak,V. M., Gutyj, B. V., Gufriy, D. F., Hariv, I. I., Khomyk, R. I., & Vasivhttps, R. O. (2018). Preclinical research of the experimental preparation “Ferosel T”. Ukrainian Journal of Veterinary and Agricultural Sciences, 1, 3−9. https://doi.org/10.15421/ujvas0101 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. Vlizlo, V. V., Fedoruk, R. S., Ratych, I. B., Vishhur, O. I., Sharan, M. M., Vudmaska, I. V. (2012). Laboratorni metody doslidzhen u biolohii, tvarynnytstvi i veterynarii. Lviv. SPOLOM [in Ukrainian]. Walter, T., Olivares, M., Pizarro, F., Munoz, C. (1997). Iron, anemia, and infection. Nutrition Review, 55 (4), 111–124. doi: https://doi.org/10.1111/j.1753-4887.1997.tb06462.x
    • Correction
    • Source
    • Cite
    • Save
    • Machine Reading By IdeaReader
    0
    References
    2
    Citations
    NaN
    KQI
    []