Опубликовать статью

Информационное партнерство

Инфоресурсы

Контакты

«

Vol. 16, Art. 36 (pp. 371-382)    |    2015       

»

Study of the protective effect of new synthetic neuropeptides at acute ethanol intoxication

Reynyuk V.L., Hovpachev A.A., Myasnikov V.A., Kolobov A.A., Halyutin D.A.

Federal State Budgetary Military Educational Establishment of High Professional Education «S.M. Kirov Military Medical Academy»
of the Ministry of Defense of the Russian Federation

Brief summary

It has been presented a comparative assessment of new neuropeptide drugs КК1, DKP9 and KRPС as the correction mean of acute poisoning with ethanol of varying severity. At the initial stage solution of the ethanol 40% has been entered intragastrically in dose 1.5 LD50 (12 g/kg), then when determined the evaluation index of protection and antidote-power neuropeptide KK1 has been used ethanol in doses of 0,8 LD50 (6 g/kg), 1 LD50 (8 g/kg), 1,25 LD50 (10 g/kg), 1.5 LD50 (12 g/kg), 1,75 LD50 (14 g/kg) and 2.0 LD50 (16 g/kg). Peptides КК1, DKP9 and KRPС has been entered intranasally in the single doses of 40 mkg/kg later 30 min after introduction of ethanol. Acute ethanol intoxication has been leaded dose-dependent disorders of the Central nervous system, body temperature, respiration in rats and also leads to death of them. The survival has been greatest when the KK1 was used poisoned rats were used in acute intoxication of alcohol in a dosage of 1,5 LD50.. Therapeutic introduction of this drug has allowed to avoid emergence of the status classified as "coma", has helped to maintain body temperature and respiratory rate, the survival has increased to 83%. In the same conditions therapy has been ineffective when peptides DKP9 and KRPС were used. The usage of peptide KK1 has a protective effect on the model of acute alcohol intoxication: the protection index has made 1.6±0.3 and the antidote power – 0,84.


Key words

ethanol; poisoning; treatment; peptides; survival; index of protection; central nervous system function

Reference list

1. Golovko, A.I. Otrezvlyaushie sredstva, izmenyaushie toksidinamiky etanola / A.I. Golovko // Biomedicinskaya himiya. – 2013. – Tom 59, vip.6. – S. 604-621.


2. Kraeva, U.V. Razrabotka naychno-organizacionnih podhodov k optimizacii lecheniya bolnih s ostrimi otravleniyami na dogospitalnom etape: dis. k-ta med. nayk / U.V. Kraeva – g. Ekaterinbyrg: YGMY, – 2013. – 140 s.


3. Golovko, A.I. Mehanizmi farmakologicheskoi aktivnosti antideprimiryushih sredstv, deistvyushih na sistemi GAMK i glytaminovoi kisloti / A.I. Golovko, V.A. Barinov V.A. Basharin [i dr.] // Biomedicinskii jyrnal Medline.ru [Elektronnii resyrs] URL: http://www.medline.ru/public/pdf/13_014.pdf/ (data obrasheniya: 20.01.2015).


4. Grebenuk, A.N. Sravnitelnaya ocenka effektivnosti peptidnih preparatov pri ostrih tyajelih otravleniyah etanolom / A.N Grebenuk, D.A. Halutin, V.L. Reinuk [i dr.] // Toksikologicheskii vestnik. – 2014. – №6. – S. 15-21.


5. Grebenuk, A.N. Ocenka effektivnosti peptidnih preparatov v kachestve sredstv korrekcii naryshenii fynkcii centralnoi nervnoi sistemi, vizvannih visokimi dozami etanola / A.N.Grebenuk, V.L. Reinuk, D.A. Halutin [i dr.] // Vestnik Rossiiskoi Voenno–medicinskoi akademii. – 2014. – №3 (47). – S. 145-149.


6. Sewald, N. Peptides: chemistry and biology / N. Sewald, H. Jakubke. // Willey–VCH Verlag GmbH. & Co., 2002. − 543 p.


7. Rykovodstvo po eksperimentalnomy (doklinicheskomy) izycheniu novih farmakologicheskih veshestv. 2-e izd., pererab. i dop. / Pod red. R.Y. Habrieva – M.: Medicina – 2005. – 832 c.


8. Deiko, R.D. Tetrapeptid i sredstvo, obladaushee cerebroprotektornoi i antiamnesticheskoi aktivnostyami / R.D. Deiko, E.A. Kampe-Nemm, A.A. Kolobov [i dr.] // Zayavka na patent RF №2013119051/04(028190) ot 25.04.2013 g.


9. Kovalickaya, U.A. Stress – protektornaya aktivnost sinteticheskogo peptida CH3CO–Lys–Lys–Arg–Arg–NH2(protektina) / U.A. Kovalickaya, V.B. Sadovnikov, U.A. Zolotarev, E.V. Navolockaya // Bioorganicheskaya himiya. – 2009. – № 35 (4). – S. 493-500.


10. Kolobov, A.A. Sredstvo obladaushee nootropnim vozdeistviem na organizm sredstv / A.A. Kolobov, A.N. Prysakov, G.V. Nikiforovich, V.M. Shpen // Patent RF №2517209 ot 06.07.2012 g.


11. Bonitenko, E.U. Modelirovanie toksicheskih kom, vizvannih veshestvami deprimiryushego deistviya / E.U. Bonitenko, A.N. Petrov, V.A. Basharin [i dr.] // Trydi instityta toksikologii, posvyashennie 75-letiu so dnya osnovaniya / Pod. red. S.P. Nechiporenko. − SPb, 2010. − S. 16-30.


12. Genes, V.S. Nekotorie prostie metodi kiberneticheskoi obrabotki dannih diagnosticheskih i fiziologicheskih issledovanii / V.S. Genes. – M.: Nayka, 1967. – 150 s.


13. Platonov, A.E. Statisticheskii analiz v medicine i biologii: zadachi, terminologiya, logika, komputernie metodi / A.E. Platonov – M.: Izd-vo RAMN, 2000. – 52 s.


14. Lyjnikov, E.A. Medicinskaya toksikologiya: nacionalnoe rykovodstvo // Pod red. E.A. Lyjnikova. – M.: GEOTAR-Media – 2012. – 928 s.


15. Markizova, N.F. Molekylyarnii kislorod i ego aktivnie formi v processah toksikokinetiki i toksikodinamiki / N.F. Markizova, A.V. Epifancev, V.A. Basharin // SPb: VMedA, – 2004. – 45 s.


16. Rico, E.P. Ethanol and acetaldehyde alter NTPDase and 5'-nucleotidase from zebrafish brain membranes / E.P. Rico, D.B. Rosemberg, M.R. Senger [et al.] // Neurochem. Int. – 2008. – №52 (1–2). – S. 290-296.


17. Nechiporenko, S.P. Antidoti v lechenii ostrih otravlenii / S.P. Nechiporenko, V.A. Barinov // Trydi instityta toksikologii, posvyashennie 75-letiu so dnya osnovaniya: Sb. st. pod red. prof. S.P. Nechiporenko. – SPb: ELBI-SPb, 2010. – S. 233-258.


18. Taslim, N. Role of mouse cerebellar nicotinic acetylcholine receptor (nAChR) α(4)β(2)– and α(7) subtypes in the behavioral cross - tolerance between nicotine and ethanol - induced ataxia / N. Taslim, K. Soderstrom, M.S. Dar // Behav. Brain. Res. – 2011. – Vol. 217. – R. 282-292.


19. Sun, Y.-P. Systemic administration of arecoline reduces ethanol – induced sleeping through activation of central muscarinic receptor in mice / Y.-P. Sun, Q. Liu, J. Luo [et al.] // Alcoholism: Clin. and Exp. Res. – 2010. – №1. – R. 150-157.