MANIFESTATIONS OF ENDOGENIC INTOXICATION IN THE LIVER IN EXPERIMENT
The study was performed at the Department of Clinical Pathophysiology, Topographical Anatomy and Operative Surgery at Kharkiv Medical Academy of Postgraduate Education in the framework of the research project “Radiotoxins pathochemical mechanisms on the body and methods of early diagnostics and correction”, state registration number 0117U000589. We studied the effect of small doses of sub-toxic sodium fluoride on the activity of microsomal hepatocytes in 40 Wistar rats populations in the subacute experiment. Analysis of results suggests the disruption of reductase activity of hepatocyte microsomes in experimental animals subjected to seeding with aqueous solutions of sodium fluoride at doses of 1/10 and 1/100 LD50, and as a result, the functioning of the electron-transport systems. Detected changes, especially on the 60th and in some cases also on the 50th day of oral administration of sodium fluoride, were associated with the restructuring of lipid environment of microsomal reductases as a result of formation of a significant amount of reactive oxygen species (ROS).The observed decrease in the overall pool of cytochrome P-450 on the 50th and especially on the 60th day of administration of sodium fluoride can be observed as an indicator of its inactivation process. The effect of inhibition of cytochrome P-450 in conditions of prolonged exposure to sodium fluoride is a rather significant fact in terms of structural integration membranes. The level of cytochrome b5 was characterized by an opposite change – an increase by 50% on the 50th day and a decrease by 47% on the 60th day of FS action. Increased activity of NAD (P) H-cytochrome-c-reductase in rats with administered sodium fluoride for one month can be considered on the one hand as a protective compensatory response, and on the other – as the cause of a more rapid flow of electrons from the reduced form of NAD (P) H in cytochrome P-450 and b5 and significant formation of ROS.
2. Dubovaya A.V. Exogenic and endogenic intoxication. Functional detoxification system. Methods of active detoxification: Health of the child, 2011, № 5 (32): P. 79-86.
3. Lake B.G., Price R.J. Evaluation of the metabolism and hepatotoxicity of xenobiotics utilizing precision-cut slices: Xenobiotica, 2013, Vol. 43: P. 41-53.
4. Effects of single exposure of sodium fluoride on lipid peroxidation and antioxidant enzymes in salivary glands of rats / P.M. Yamaguti, A. Simoes, D.N. Souza [et. al.] // Oxidat. Med. Cell Long Article, ID674593, 7 hages.http://dx.doi.org/10.1155/2013 / 674593
5. Anzenbacher P.,Zanger U.M. Metabolism of drugs and other xenobiotics: Wiley-VCH, 2012. – 724 p.
6. Danielle K., Pelkonen O., Ahokas T. Hepatocytes: the powerhouse of biotransformation: Int. J. Biochem. Cell Biol., 2012, Vol. 4: P. 257-265.
7. Schlezinger J.J., White R.D., Stegeman J.J., Oxidative inactivation of cytochrome P-450 1A (CYP1A) stimulated by 3,3`, 4,4`-tetrachlorobiphenyl: production of reactive oxygen by vertebrate CYP1As: Molecular Pharmacology, 1999, Vol. 56: P. 588-597.
8. Porter T.D. The roles of cytochrome b5 in cytochrome P450 reactions: Biochem. Mol. Toxicol., 2002, Vol. 16, № 6: P. 311-316.
9. Danielle K., Pelkonen O. Hepatocytes: the powerhouse of biotransformation: Int. J. Biochem. Cell Biol., 2012, Vol. 44: P. 257-265.
10. Bagmut I. The impact on the state oligoesters microsomal monooxygenase system hepatocytes white rats in the experiment. Strategic question of Science, 2014: materials of international IX scientific conference. Polska, Przemysl: «Nauka and studia», 2014, V. 26: P. 41-45.
11. Bagmut I.Yu., Klimenko N.A., Zhukov V.I. Status of hydroxyl monooxygenase system hepatocytes under the influence of different doses of oligoesters. Education and science without borders – 2013: materials of international IX scientific conference. Polska, Przemysl: “Nauka and studia”, 2013, V. 2: P. 62-67.
Klimenko M.O., Kucheryavchenko M.O., Bagmut I.Yu. Long subtoxic Laproxide influence on the metabolic activity of monooxygenase system of hepatocytes in subacute experiment. Problems of continuing medical education and research, 2014, 4 : P. 57-60.