RESPIRATORY AND REDUCTIVE ACTIVITY OF A MICROSOMAL FRACTION OF RAT'S LIVER UNDER THE ACTION OF OLIGOESTERS OF POLIATOMIC ALCOHOLS

Bondareva A. V.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

The study of mechanisms of pathological processes is an important direction in modern science. The widespread xenobiotics are polyatomic alcohols oligoethers under a technical name of "Laprols" (OLE-LP), which are characterized by a fairly significant amount of chemical industry and widely used in various sectors of the agriculture (as a basis for industrial production of plastics, polyurethane foams, paints, detergents, hydraulic and cooling substances, etc.). Some xenobiotics are harmful to human health, fauna and flora, form the unhealthy and pathological conditions. Some ways of adaptation to the action of xenobiotics is generated in the evolution, which include the key role in biochemical mechanisms of their neutralization. This is due to the operation monooxygenase system (MOS) in smooth endoplasmic reticulum. Two enzyme systems that oxidize NADPH2 and NADH2 are located in a microsomal membrane of hepatocyte. NADH-dependent system acts with cytochrome P-450 as the final link, NADH-system — with cytochrome b5 as an electron acceptor. It was determined that the activation of the MOS can leads to oxidative stress. Violation of MOS of hepatocytes is a cause of the disbalance of homeostasis and development of pathological processes. This topic has not been studied in conditions of prolonged exposure to new representatives OLE-LP, and its study is necessary to disclose the mechanism of a biological action and the development of means of their correction. Designs of OLE-LP number 502 (polioksypropilenhlikol) and 503 (polioksypropilentryol) with regulated physicochemical characteristics are used in the research work. The experimental program conducted on the mature rats of Wistar, having weight 180-220 g. The animals were given water solution with substances once a day for 45 days in doses of 1/10 and 1/100 LD50. The animals of the control group received of drinking water. Each group had 10 animals. Rats were anesthetic by sodium thiopental in doses of 50 mg / kg, then they were decapitated. Subcellular fractions of rat liver were held by differential centrifugation. The study was conducted in the dynamics of observation: 15, 30, 45th day after the start of the experiment. The results indicate biochemical disturbance of neutralization in the liver of rats, primarily in MOS. This could lead to disruption of the electron transport chain, the emergence of reactive metabolites. Increase of respiratory activity in rat's liver (15th day of action at 1/10 LD50; 15th and 30th day of action at 1/100 LD50) is an adaptive reaction of the organism. The increase of rate of oxygen consumption in the presence of NAD (P) H and the activity of NAD (P) H-cytochrome c-reductase on the 15th day in doses of substances action 1/10 1/100 LD50 was found. Decrease of oxygen consumption and the activity of NAD (P) H-reductase on the 30th day of action of substances in 1/10 LD50 dose with increasing dose 1/100 LD50 was noted. It is concluded that the increase of respiratory and reductive activity of microsomes, hepatocytes is an adaptive response of the body to the introduction of substances associated with the launch of the process of their removal and possibility of reactive oxygen species generation. The respiratory depression and microsomal reductase activity on 45 th day of action of substances in both doses were determined. These disorders are those of the pathogenetic links of oligoesters action. It must be taken into account when the means of correction will be developed.

oligoesters, rats, microsome of hepatocyte, oxygen uptake rate, activity of NAD(P)H-cytochrome c-reductase

• 1. Жуков В.И. Медико-биологические аспекты проблемы охраны водных объектов от загрязнения поверхностно-активными веществами / В.И. Жуков, Р.И. Кратенко, Ю.К. Резуненко [и др.]. – Х.: Торнадо, 2000. – 394 с.

• 2. Каган В.Е. Изучение механизма инициирования ферментативного НАДФН-зависимого перекисного окисления липидов в мембранах эндоплазматического ретикулума / В.Е. Каган, Е.М. Сербинова, А.А. Минин // Биохимия. – 1985. – Т. 50, № 6. – С. 986-991.

• 3. Капранов С.В. Принципиальная схема влияния факторов среды жизнедеятельности на организм человека / С.В. Копранов // Довкілля та здоров’я. — 2011. — № 2. — С. 23-26.

• 4. Крыжановский В.К. Технология полимерных материалов. Синтез. Модификация. Технологическое оформление. Рециклинг. Экологические аспекты / В.К. Крыжановский. — СПб.: Профессия, 2008. – 534 с.

• 5. Кузнецова Э.Э. Микросомальное окисление в физиологических и патологических процессах / Э.Э. Кузнецова, В.Г. Горохова, А.Г. Горохов [и др.] // Бюллетень ВСНЦ СО РАМН. – 2007. — № 4 (56). – С. 170-180.

• 6. Марченко М.М. Біохімічна трансформація ксенобіотиків у організмі / М.М. Марченко, О.В. Кеца, М.М. Великий. — Чернівці: Чернівецький нац. ун-т, 2011. — 280 с.

• 7. Орехович В.Н. Современные методы в биохимии / В.Н. Орехович. — М.: Медицина, 1977. — 371 с.

• 8. Сидорин Г.И. Адаптация как основа защиты организма от вредного действия химических веществ / Г.И. Сидорин, Л.В. Луковникова, А.Д. Фролова // Рос. хим. журнал. — 2004. — № 2. — С. 44-50.

• 9. Цудзевич Б.О. Ксенобіотики: накопичення, детоксикація та виведення з живих організмів / Б.О. Цудзевич, О.Б. Столяр, І.В. Калініна [та ін.]. — Тернопіль: Видавництво ТНТУ ім. І. Пулюя, 2012. — 384 с.

• 10. Юрченко П.О. Монооксигеназні активності печінки щурів в умовах гіперглікемії та гіперкетонемії, індукованих введенням стрептозотоцину та дексаметазону / П.О. Юрченко, О.Х. Герич // Буковинський медичний вісник. — 2005. — Т. 9, № 2. — С. 55-56.

• 11. Anzenbacher P. Metabolism of drugs and other xenobiotics / P. Anzenbacher, U.M. Zanger. – Wiley-VCH, 2012. – 724 p.

• 12. Danielle K. Hepatocytes: the powerhouse of biotransformation / K. Danielle, O. Pelkonen, T. Ahokas // Int. J. Biochem. Cell Biol. – 2012. – Vol. 44. – P. 257-265.

• 13. Dibyajyoti Saha. Xenobiotics, oxidative stress, free radicals Vs. Antioxidants: dance of death to heaven’s life / Dibyajyoti Saha, Ankit Tamrakar // Asian J. Res. Pharm. Sci – 2011. – Vol. 1, Issue 2. – P. 36-38.

• 14. Dogra S.C. Transcriptional activation of cytochrome P450 genes by different classes of chemical inducers / S.C. Dogra, M.L. Whitelaw, B.K. May // Clin. Exp. Pharmacol. Physiol. – 1998. – Vol. 25 (1). – P. 1-9.

• 15. Fotman H. Signaling functions of reactive oxygen species / H. Fotman, M. Maiorino, F. Ursini // Biochemistry. – 2010. – Vol. 49, № 5. – P. 835-842.

• 16. Guengerich F.P. Cytochrome P450 oxidations in the generation of reactive electrophiles: epoxidation and related reactions / F.P. Guengerich // Arch. Biochem. Biophys. – 2003. – Vol. 409, № 1. – Р. 59-71.

• 17. Ingelman-Sundberg M. Genetic susceptibility to adverse effects of drugs and environmental toxicants. The role of the CYP family of enzymes / M. Ingelman-Sundberg // Mutat. Res. – 2001. – Vol. 482 (1-2). – P. 11-19.

• 18. Karuzina I.I. Hydrogen peroxide-mediated inactivation of microsomal cytochrome P-450 during monooxygenase reactions / I.I. Karuzina, A.I. Archakov // Free Rad. Biol. Med. — 1994. – Vol. 17, № 6. — P. 557-567.

• 19. Kotelevtsev S.V. Some priorities and fundamental concepts in contemporary issues of ecological and molecular toxicology, biogeochemistry and ecological geochemistry: ecotoxicants including membranotropic xenobiotics and metals / S.V. Kotelevtsev, S.N. Orlov, D.N. Matorin, K.N. Novikov, A.P. Sadchikov, A.V. Smurov, V.V. Ermakov, S.A. Ostroumov // Ecological Studies, Hazards, Solutions. – 2013. – Vol. 19. – P. 122-124.

• 20. Lewis D.F. Evolution of the cytochrome P450 superfamily: sequence alignments and pharmacogenetics / D.F. Lewis, E. Watson, B.G. Lake // Mutat. Res. – 1998. – Vol. 410 (3). – P. 245-270.

• 21. Omiecinski C.J. Xenobiotic metabolism, disposition and regulation by receptors: from biochemical phenomenon to predictors of major toxicities / C.J. Omiecinski, J.P.V. Heuvel, G.H. Perdew, J.M. Peters // Toxicological Sciences. – 2011. – 120 (S1). – P. 49-75.

• 22. Rahal А. Oxidative stress, prooxidants and antioxidants: the interplay / A. Rahal, A. Kumar, V. Singh, B. Yadav, R. Tiwari, S. Chakraborty, K. Dhama // Biomed. Research International. – 2014. – 19 p.

• 23. Zanger U.M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation / U.M. Zanger, M. Schwab // Pharmacology & Therapeutics. – 2013. – Vol. 138, Issue 1. – P. 103-141.

«Bulletin of problems biology and medicine» Issue 1 part 2 (127), 2016 year, 72-76 pages, index UDK 577.152.1:616.36-092.9-099:543.385