You are here

Preclinical trials of immunomodulating drug Arselan on laboratory mice

Conducting Toxicological control of veterinary drugs prevent possible infringement of metabolism, the negative effect on the organs and tissues, the occurrence of side effects and remote consequences, creates prerequisites for determining the optimal therapeutic doses, ways and terms of use, ways and removal out of the body, which in turn encourages the development of new highly competitive products.

The aim of the study was to conduct pre-clinical trials imunomodelling drug Arselan: to determine the acute toxicity and revealing of possible danger of the drug in a single injection in the body of animals; set the maximum therapeutic, toxic and lethal doses. For Toxicological studies used a Mature, healthy white mice that were fed the standard granulated feed for standards, according to the rules. Before the beginning of experience the mice were observed for 14 days.

Immunomodulatory agent Arselan dosage 50, 100, 200, 400, 600, 800 and 1000 mg/kg for intragastric introduction to white mice showed no toxicity, no animal was killed. After the drug in a dose of 5000 mg/kg (fifth study group) and in mice watched the suppression of the General (lethargy), delayed reaction to external stimuli, anorexia, tachypnea, tremor, a slight hyperemia ears and paws. This state of research in mice lasted about 4 hours, then watched restoration of natural, no animal was killed. Every 2 days mice of all groups were weighed. Found that even in the fifth experimental group after the experiment, the mass of the mice was 7 g greater than in control, the difference was 26 %. The study indicated that the dose that did not cause death of animals for intragastric administration (LD0)amounted to 5000 mg/kg of body weight, and the introduction of higher doses impossible through physiological characteristics (low weight of a body) mice. Thus, according to the state standard 12.1.007-76 can be concluded that the drug Arselan is non-toxic for animals.

In case of application of the arselan laboratory animals indicators of the morphological composition of blood was within norm. The erythrocyte sedimentation rate (ESR) has not changed during the whole experiment and amounted to 1 mm in all experimental groups, as for 7-th and 14-th day. No marked changes in the number of platelets in the peripheral blood of animals. The researched mice observed a trend towards increasing the number of red blood cells and increase of the concentration of hemoglobin, which pointed to the stimulating effect of the arselan on eritrotsitoz. Gematokrita value had a tendency of growth only in the 4-th and 5-th research groups which were introduced with the greatest concentration of imunomodelling of the drug. Despite the obtained data the peripheral blood of animals, we can assume that Arselan contributes to stimulation of metabolism in organism, maintenance of ionic homeostasis, etc.

In result of studies it is established that imunomodelling the drug in doses of Arselan 50, 100, 200, 400, 600, 800 and 1000 mg/kg for intragastric introduction to white mice showed no toxicity, no animal was killed (LD0 is 5000 mg/kg body weight of the animal; GOST 12.1.007-76). The tendency to increase the number of red blood cells and increase of the concentration of hemoglobin in the blood of experimental animals, which used Arselan, indicates the stimulating effect of the drugs on eritrotsitoz. Perspective direction of our research will be the selection of therapeutic doses to arselan for productive animals, and also to study the effect of immunomodulator on changes of the natural resistance of cattle and pigs.

Key words: arselan, acute toxicity LD50, LD100.

1. Stefanov O.V. Doklinichni doslidzhennja likars'kyh zasobiv: Metodychni rekomendacii' / O.V. Stefanov. – Kyi'v: Avicenna, 2001. – 528 s.

2. Doklinichni doslidzhennja veterynarnyh likars'kyh zasobiv / [I.Ja. Kocjumbas, O.G. Malyk, I.P. Paterega ta in.]; za red. I.Ja. Kocjumbasa.– L'viv: Triada pljus, 2006.– 360 s.

3. Preclinical assessment of the efficacy of mycograb, a human recombinant antibody against fungal HSP90 / [R.C. Matthews, G. Rigg, S. Hodgetts at all] // Antimicrob Agents Chemother, 2003. – Vol. 47. – P. 2208–2216.

4. Employment of adult mammalian primary cells in toxicology: In vivo and in vitro genotoxic effects of environmentally significant N-nitrosodialkylamines in cells of liver, lung and kidney / [B.L. Pool, S.Y. Brendler, U.M. Liegibel et al.] // Environmental Molecular Mutagenesis. – 1990. – Vol. 15. – P. 24–35.

5. Faqi A.S. A Comprehensive Guide to Toxicology in Preclinical Drug Development / A.S. Faqi. – Imprint: Academic Press, 2012. – 1024 p.

6. Vyvchennja likars'kyh zasobiv ta ekspertyzy materialiv doklinichnogo vyvchennja likars'kyh zasobiv: Nakaz MOZ Ukrai'ny vid 14.12.2009 № 944 – Rezhym dostupu: http://zakon. =z0053-10/.

7. Lojt A.O. Profilakticheskaja toksikologija: Rukovodstvo dlja toksikologov-jeksperimentatorov / A.O. Lojt, M.F. Savchenkov. – Irkutsk: Izd-vo Irkut. un-ta, 1996. – 279 s.

8. GOST 12.1.007-76.SSBT. Vrednye veshhestva. Klassifikacija i obshhie trebovanija bezopasnosti. – Vved. 01.01.77; Proveren 01.10.81; Izmenjon № 1; Pereizdan 01.12.81. – M.: Izd-vo standartov, 1982. – 6 s.

9. Kosenko M.V. Toksykologichnyj kontrol' novyh zasobiv zahystu tvaryn [metod. rekom.] / M.V. Kosenko, O.G. Malyk, I.Ja. Kocjumbas – K., 1997. – 33 s.

10. Haitov R.M. Otechestvennye imunotropnye lekarstvennye sredstva poslednego pokolenija i strategija ih primenenija / R.M. Haitov, B.V. Pinegin, T.M. Andronov // Farmakologija. – K., 2002. – 130 s.