EUROMEDICAHanover6-7 Juni 2008 |
Advanced methods of diagnosis,
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European Academy of Natural Sciences, HanoverEuropean Scientific Society, HanoverRussian Academy of Natural Sciences, Moscow |
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| S.U. Klepikova E.A. Krasnov O.P. Kolesnikova A.E. Prosenko |
DITRETIOPHENYL A NEW WATER-SOLUBLE ANTIOXIDANT WITH IMMUNODEPRESSIVE ACTIVITY |
| Novosibirsk State Medical University, Novosibirsk, Russia Siberian State Medical University, Tomsk, Russia Scientific Center of Clinical Immynal, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk, Russia Scientific Research Institutes of Chemistry of Antioxidants, Novosibirsk, Russia |
Sulphur derivatives of the spatially-difficult phenols present great interest among water-soluble antioxidants, characteristic feature of which is their expressed antioxidant activity. Ditretiophenyl (3-(3, 5 di-tret-butyl-4-hydr ophenyl)propyltiosulphonat sodium) is crystal powder of white colour, with a specific smell and a bitterish taste. In the Uf-spectrum there is one maximum of absorption at 277 nm. Ditretiophenyl possesses hydro properties: it is easily dissolve in water, dissolve in spirits and very little in chloroform and benzene.
Ditretiophenyl in water solutions under the influence of acids and the bases form at once a disulphide, or through a stage of formation in the intermediate product – tiole, on the hydrolysis process influence: percentage of acid in the reactionary environment, temperature and duration of reaction.
The critical toxicology of ditretiophenyl in peritoneum by mice is 175mg/kg (LD50). On the model of Cu2+ - induction of oxidation metyloleate at 60°C in water - emulsion to environment (calculate the induction period), and on the model Cu2+ - (5MKM CuSO4) and Fe2+- induction (25MKM FeSO4) oxidation of LNP at 37°C in a current of 30 minute (by a fluorescent method measured accumulation reacting with thiobarbiturat acid of products), the expressed antioxidant activity ditretiophenyl is established in comparison with structural analogues and known antioxidants: ionol and phenozan potassium.
A research on immunotropic properties of the ditrethiofenyl was carried out in two dose 20 mgk/ml and 200 mgk/ml for the spontaneous and ConA, PWM, LPS mitogen - stimulated proliferation of the cells of spleen in the culture in vitro. It is discovered, that the ditrethiofenyl dose-dependent suppress the proliferation of immunocompetent cells by over 70%. The result of experiments in vivo on studying of as much as possible transferable dose ditretiophenyl (35 mg/kg) in peritoneum introduction during 7 days at mice showed, that ditrethiofenyl possesses an immunodepressive activity, the lower level nucleus contain cells of peripheral blood more than on 20 %. Ditretiophenyl in a dose of 10 mg/kg the influence on primary gymoral the immune answer (IgM) in vivo - by absolute and relative quantity antibody cells in a spleen, show authentic results in absolute quantity IgM on 40 % and 29 %, and relative quantity IgM on 27 % and 23 %. These immunodepression activities have been tested on experimental model immunocomplex gromerynephrit. Ditretiophenyl in a dose of 35mg/kg in peritoneum every other day authentically reduces cardinal number the albumen into the urine that testifies to an anti-inflammatory activity.
Research radioprotection activity are shown that at low concentration ditrethiofenyl in doses of 2 mg/kg and 10 mg/kg entered in peritoneum in volume of 0,5 ml daily in a current of four days, insignificantly increases the life expectancy of mice after a lethal irradiation (in a dose 850R), however not exceeding maximal of 10 days. At increase in a dose of 20 mg/kg the proof rise to 90% of survival rate of the animals to a sharp lethal irradiation is observed.
Thus, ditrethiofenyl the water-soluble compounds, showing in experimental models in vitro and in vivo expressed antioxidant, anti-inflammatory and radioprotection activities, can find application as a nontoxic immunodepressant.
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