Медико-биологический
информационный портал
для специалистов
 
БИОМЕДИЦИНСКИЙ ЖУРНАЛ Medline.ru

СОДЕРЖАНИЕ ЖУРНАЛА:
Физико-химическая биология

Клиническая медицина

Профилактическая медицина

Медико-биологические науки


АРХИВ:

Фундаментальные исследования

Организация здравохраниения

История медицины и биологии



Последние публикации

Поиск публикаций

Articles

Архив :  2000 г.  2001 г.  2002 г. 
               2003 г.  2004 г.  2005 г. 
               2006 г.  2007 г.  2008 г. 
               2009 г.  2010 г.  2011 г. 
               2012 г.  2013 г.  2014 г. 
               2015 г.  2016 г. 

Редакционная информация:
        Опубликовать статью
        Наша статистика


 РЕДАКЦИЯ:
Главный редактор

Заместители главного редактора

Члены редколлегии
Специализированные редколлегии


 УЧРЕДИТЕЛИ:
Федеральное государственное бюджетное учреждение науки
"Институт токсикологии Федерального медико-биологического агентства"
(ФГБУН ИТ ФМБА России)

Институт теоретической и экспериментальной биофизики Российской академии наук.

ООО "ИЦ КОМКОН".




Адрес редакции и реквизиты

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

ISSN 1999-6314

Российская поисковая система
Искать: 


«
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





(The article in PDF format. For preview need Adobe Acrobat Reader)



Open article in new window

Reference list

1. Bajaj S. Review article: the modern management of hepatic encephalopathy.//Aliment Pharmacol. Ther.2010. vol. 31(5). pp. 537-547.


2.Nencki M., Pawlow J.P., Zaleski J. Ueber den Ammoniakgehalt des Bluttes und der Organe. Die Harnstoffbildung bei den Saugetieren.// Arch. Exp. Pathol. Pharmakol. 1896. vol.37. pp.26-51.1896.


3. Eck N.V. K voprosu o perevyazkie vorotnoij veni. Predvaritelnoye soobshtshjenye. // Voen. Med. J ( Rus). 1877. vol.130. N 2. .p1.


4. McDermott W.V. Jr. The role of ammonia intoxication in hepatic coma.// Bull. N. Y. Acad. Med. 1958. vol. 34(6). pp.357-65.


5. Sherlock S. Hepatic coma. //Gastroenterology. Official publication of the American Gastroenterological Association. 1961. vol.07. pp. 1-8.


6. Rose C.F. Ammonia-lowering strategies for the treatment of hepatic encephalopathy.// Clin Pharmacol Ther. 2012. vol.92. pp.321-31.


7. Kircheis G., Wettstein M., Dahl S.V., Haussinger D. Clinical efficacy of L-ornithine-Laspartate in the management of hepatic encephalopathy. [Review].// Metab. Brain Dis. 2002 vol.17. pp. 453-62.


8. Acharya S.K., Bhatia V., Sreenivas V. et al. Efficacy of L-ornithine L-aspartate in acute liver failure: a double-blind, randomized, placebo-controlled study.//Gastroenterology. 2009 vol.136(7). pp.2159-68.


9. Jalan R., Jalan K. N. Compositions Comprising Ornithine And Phenylacetate Or Phenylbutyrate For Treating Hepatic Encephalopathy.// Patent: US 20080119554 A1. 2008.


10. Braissant O, McLin V.A., Cudalbu C. Ammonia toxicity to the brain. //J Inherit Metab Dis. 2013. vol.36. pp. 595-612.


11. O'Connor J.E., Costell M., Grisolía S. Protective effect of L-carnitine on hyperammonemia.// FEBS Lett. 1984. vol.166(2). pp. 331-4.


12. Coude F.X., Sweetman L., Nyhan W.L. Inhibition by propionyl-coenzyme A of N-acetylglutamate synthetase in rat liver mitochondria. A possible explanation for hyperammonemia in propionic and methylmalonic acidemia.// J Clin. Invest. 1979. vol. 64(6). pp.1544-51.


13. Hindfelt B., Siesjö B.K. Cerebral effects of acute ammonia intoxication. II. The effect upon energy metabolism. //Scand J Clin Lab Invest. 1971. vol. 28(3). pp.365-74.


14. Kosenko E., Kaminsky Y., Grau E. et al. Brain ATP depletion induced by acute ammonia intoxication in rats is mediated by activation of the NMDA receptor and Na+,K(+)-ATPase. //J Neurochem. 1994. vol. 63(6). pp. 2172-8.


15. Häussinger D., Görg B. Interaction of oxidative stress, astrocyte swelling and cerebral ammonia toxicity. //Curr. Opin. Clin. Nutr. Metab. Care. 2010. vol.13. pp.87- 92.


16. Montoliu C., Llansola M., Monfort P. et al. Role of nitric oxide and cyclic GMP in glutamate-induced neuronal death. //Neurotox Res. 2001 . vol.3(2). pp.179-88.


17. Brusilow S.W., Koehler R.C., Traystman R.J., Cooper A.J. Astrocyte glutamine synthetase: importance in hyperammonemic syndromes and potential target for therapy.// Neurotherapeutics. 2010. vol.7. pp.452-70.


18. Shawcross DL, Davies NA, Williams R, Jalan R. Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis.// J Hepatol. 2004. vol.40(2). pp.247-54.


19. Lux HD. Ammonium and chloride extrusion: hyperpolarizing synaptic inhibition in spinal motoneurons. //Science. 1971. vol.73. pp. 555-7.


20. Raabe W, Gumnit RJ. Disinhibition in cat motor cortex by ammonia. // J Neurophysiol. 1975. vol.38. pp. 347-55.


21. Rangroo Thrane V, Thrane AS, Wang F, Cotrina ML, Smith NA, Chen M, et al. Ammonia triggers neuronal disinhibition and seizures by impairing astrocyte potassium buffering.// Nat Med. 2013. vol.19. pp.1643-8.


22. 6. Dynnik V.V., Kononov A.V., Sergeev A..I, Zinchenko V.P. To break or to brake neuronal network accelerated by ammonium ions? //PLoS ONE, 2015, vol. 28, N10(7), pp. 1-30. e0134145, DOI: 10.1371/journal.pone.0134145. PMID:26217943


23. Turovsky E.A., Turovskaya M.V., Dolgacheva L.P, et al. Acetylcholine promotes Ca2+ and NO-oscillations in adipocytes implicating Ca2+→NO→cGMP→cADP-ribose→Ca2+ positive feedback loop--modulatory effects of norepinephrine and atrial natriuretic peptide. // PLoS One. 2013. vol.8(5). pp. 1-18.e63483. doi: 10.1371/journal.pone.0063483. PMID: 23696827


24. Kloiber O., Banjac B., Drewes L.R. Protection against acute hyperammonemia: the role of quaternary amines.// Toxicology. 1988. vol.49(1). pp.83-90.


25. Malaguarnera M., Pistone G., Astuto M. et al. L-Carnitine in the treatment of mild or moderate hepatic encephalopathy. //Dig Dis. 2003


. vol.21(3). pp.271-5.


26. Babak O.Ya., Frolov V.M., Harchenko N.V. ?GLYTARGIN-farmakologicheskoe deistvie i klinicheskoe primenenie?. Harkov. Izd.?Elton-2?. 2005.455 s.


27. Bogomolov P.O., Macievich M.V., Yvarova O.V. i dr. Issledovaniya na effektivnost i bezopasnost ispolzovaniya mnogokomponentnogo sostava ?Helper-1? y pacientov s pechenochnoi encefalopatiei na fone cirroza pecheni virysnoi etiologii. // Cb. statei ?Receptori i vnytrikletochnaya signalizaciya?. Otv. Red. Zinchenko V.P. i Berejnov A.V. Moskva. Izd. OOO ?IDV. Ema?. 2013. t.2. str.417-421.


28. Grishina E.V., Galimova M.H., Djafarov R.H. et al. Induction of cyclosporine-sensitive mitochondrial permeability transition pore by substrates forming acetyl-CoA under normal conditions and in type 2 diabetes. // Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology.2016. vol?10(1). pp.11-18.



Свидетельство о регистрации сетевого электронного научного издания N 077 от 29.11.2006
Журнал основан 16 ноября 2000г.
Выдано Министерством РФ по делам печати, телерадиовещания и средств массовых коммуникаций
(c) Перепечатка материалов сайта Medline.Ru возможна только с письменного разрешения редакции

Размещение рекламы

Rambler's Top100