Marakushin D. I.

THE INFLUENCE OF OXYETHYLIZED NONYLPHENOLS AND THEIR DERIVATIVES ON THE ACTIVITY OF THIOLDISULFIDE SYSTEM IN RATS

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About the author:	Marakushin D. I.
Heading	EXPERIMENTAL MEDICINE
Type of article	Scentific article
Annotation	The purpose of the present work was to study the long-term effects produced by a group oxyethylized nonylphenols and their derivatives at doses of 1/10 and 1/100 DL50 on activity of thioldisulfide system by determination of content of thiol groups and disulfide bonds in the membrane proteins of rats erythrocytes. The standards of compounds with scheduled physical-chemical properties were used in the work: OENP with number of oxyethylized groups 6, 8, 12 (OENP 6,8,12) and CM-OENP with number of oxyethylized groups 4, 6 (CM-OENP 4,6). The experiments were carried out on white rats of WAG population. Every day before feeding they received orally, through a metal probe, aqueous solutions of compounds with 1/10 and 1/100 of LD50. The duration of subacute influence was 45 days. 15 animals were in every group. Half-lethal doses (LD50) were determined: at the levels of 4,2 g/kg; 5.1 g/kg; 3,4 g/kg of the animal weight respectively for OENP6, OENP8 and OENP12; at the levels of 6,1 g/kg; 2,2 g/kg of the animal weight respectively for CM-OENP4 and CM-OENP6. The experiments on white rats were performed in compliance with the international principles of the European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes. The membranes of erythrocytes were selected by hypoosmotic hemolysis with following sedimentation undergo centrifugation 6000 revo during 10 minutes. The content of thiol groups and disulfide bonds in the membrane proteins of erythrocytes was determined by the method of direct and reverse amperometric titration. The statistical data analysis was performed with the usage of computer programs for statistical data handling Statistica 6.1 (StatSoft, Inc., the USA). Results of the study on the influence of oxyethylized nonylphenols and their derivatives revealed statistically significant (p<0,001), comparatively with the control, a decrease of content of thiol groups on 45 day of monitoring. A dose 1/10 of LD50 was more toxic, than 1/100 of LD50. So, CM-OENP6, OENP12, OENP6, OENP8 and CM-OENP4 at a dose of 1/10 LD50 decreased the content of thiol groups, comparatively with the control, accordingly by 2; 1,8; 1,7; 1,5 and 1,2 times, at a dose of 1/100 LD50 – by 1,8; 1,6; 1,7; 1,3 and 1,1 times. On this background the statistically significant (except action of OENP4 at a dose 1/10 of LD50; р=0,299) an increase of quantity of disulfide bonds in the membrane proteins of erythrocytes of experimental animals. CM-OENP6, OENP12 caused more expressive action: they increased (р<0,001) at doses of 1/10 and 1/100 LD50 by 2 times. OENP6, OENP8 and CM-OENP4 at a dose of 1/10 LD50 increase the level -S-S- bonds, respectively, by 1,7; 1,5 and 1,4 times, at a dose of 1/100 LD50 – by 1,5; 1,2 and 1,1 times. In the membrane of erythrocytes oxyethylized nonylphenols and their derivatives caused statistically significant (p<0,013), comparatively with the control, an increase of thiol-disulfide coefficient: more expressive for CM-OENP6 (by 4,6 times), least – for CM-OENP4 (by 1,6 time). Least toxic among all studied compounds - CM-OENP4 at a dose of 1/100 LD50 also caused an increase of thiol-disulfide coefficient, but statistically nonsignificant (р=0,071). The decrease of content of thiol groups in the membrane proteins of erythrocytes on a background of the rise of disulfide bonds in conditions of the long-term influence of oxyethylized nonylphenols and their derivatives. The revealed violation of the balance in thioldisulfide system toward the oxidizing equivalents testifies about the development of processes of oxidizing modification of proteins, lipid peroxidation on the background of decrease of antioxidative resources, nonspecific resistance of an organism of experimental animals during the long-term influence of oxyethylized nonylphenols and their derivatives.
Tags	oxyethylized nonylphenols, thioldisulfide system, membrane of erythrocytes
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Publication of the article	«World of Medicine and Biology» №2(50) 2 part 2015 year, 134-138 pages, index UDK 616-099-092.9:543.395:612.015.11