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Институт теоретической и экспериментальной биофизики Российской академии наук.


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199406, Санкт-Петербург, ул.Гаванская, д. 49, корп.2

ISSN 1999-6314

Российская поисковая система

Vol. 16, Art. 96 (pp. 1077-1098)    |    2015       

Selection of complex commpositions of protectors of hyperammonemia and acute hepatic encephalopathy
Grishina E.V.1, Kravtchenko I.N.2, Lobanov A.V.2, Sergeev A.I.3, Sadovnikova E.S.2, Dynnik V.V.1

1Institute of Theoretical and Experimental Biophysics,Russian Academy of Sciences,
Institutskaya Street 3, Pushchino, Moscow Oblast, 142290 Russia
2Pushchino Branch of the Institute of bioorganic chemistry,Russian Academy of Sciences,
Institutskaya Street 6, Pushchino, Moscow Oblast, 142290 Russia

3Institute of Cell Biophysics,Russian Academy of Sciences, Institutskaya Street 3, Pushchino, Moscow Oblast, 142290 Russia

Brief summary

The purpose : selection, and testing on animal models of hyperammonemia of various compositions of natural substances, that can effectively reduce critical concentrations of ammonium ion (NH4+) in the blood and tissues and prevent the development of acute hepatic encephalopathy (brain dysfunction) and death of the animals. The model of acute hyperammonia was used. This model is based on intraperitoneal administration of lethal doses NH4Cl (LD100) to rats and mice, without or in combination with other hepatotoxins (propionate Na, CCl4, etc.). Results: Screening of the efficiency of individual substances, as well as of their pairs or triple combinations, etc was performed. These substances were taken from the classes of amino and carboxylic acids, methylamines, etc. The composition comprising L- ornithine + L-aspartate (LoLa, Pharmaceutical preparation ?HepaMerz") was used as reference embodiment.t was shown that only the compositions comprising: (1) L- glutamate, succinate, L- arginine, L- carnitine, L- acetylcarnitine and betaine (administered dose of 1.25 g / kg), (2) L- ornithine L-aspartate ( 1.25 g / kg) and (3) L- arginine, L- carnitine and betaine (3 g / kg) may provide 100% survival of mice, being injected 15 min before the administration of NH4Cl (LD100 = 16.0-16.5 mmol / kg). In contrast to mice, the survival of rats upon administration of the composition (3) was 60%, due to poor tolerance of animals to such doses of preparation. At combined action of NH4Cl and other toxins, the composition (1) was the most effective.

Key words

hyperammonemia, hepatic encephalopathy, scrinnig of hepatoprotectors and protectors of hepatic encephalopathy

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