SUBACUTE TOXICITY STUDY OF CHONDROITIN SULFATE SOLUTION IN TERMS OF THE OVERALL ANALYSIS AND BLOOD LEUKOCYTE COUNTS IN RATS

Коrotkiy O. G., Voyeykov А. І., Falalyeyeva Т. M., Beregova Т. V., Ostapchenko L. I.

BIOLOGY

Scentific article

Introduction. Chondroitin sulfate, the active substance of chondroprotectors, is no fixed length polysaccharide, and hence the molecular weight. So the emergence of a new chondroprotectors from chondroitin sulfate requires thorough research as its effectiveness and toxicity, because in different molecular weight can vary bioavailability, cumulative properties, output and others. Objective. The aim of the study was to evaluate the subacute toxicity of chondroitin sulfate sodium (CHSS), the active substance of new chondroprotector «Drastop», on indicators of global blood analysis and leukocyte formula in rats. Methods. Experiments conducted in accordance with international principles of the European Convention for the Protection of vertebrate animals used for experimental and other scientific purposes, according to the Law of Ukraine of 21.02.2006 № 3447-IV «On protection of animals from cruelty». The studies were performed on 80 white laboratory Wistar rats weighing 180-260 g. Research has focused on obtaining data on the toxicity of CHSS for a limited duration of its administration, which was 14 days. Fence biomaterial performed on the 15th day after the start of CHSS administration. The studied doses were determined based on the results obtained in the study of acute toxicity CHSS. According to these results, CHSS belongs to the class of practically non-toxic substances, as well as CHSS in dose of 1000 mg/kg didn’t cause deaths in groups of mice and rats. Thus, we believe that the dose of 1000 mg/kg is the maximum tolerated for a single injection (LD0). Therefore, for subacute toxicity studies we chose three doses, the maximum tolerated dose for single injection (LD0) — 1000 mg/kg, 3/5 LD0 (600mg/kg) and 1/5 LD0 (200mg/kg). The level of hemoglobin in the blood was determined by Sali, color index — by calculation method. Erythrocyte sedimentation rate was determined by Panchenkov, hematocrit was determined by centrifugation method. Blood smears were stained by Papenheym, and in Goryayev camera we determined the composition of leukocyte formula. Comparing the difference between control and experimental parameters was performed using Student t-test for independent samples. Results. CHSS in the doses of 200 and 600 mg/kg did not influence on parameters of global analysis of blood. But in dose 1000 mg/kg CHSS caused slight but statistically significant reduction in the number of erythrocytes and the increase in the number of leukocytes in males. Also it increased erythrocyte sedimentation rate in males and females. CHSS in the doses of 200 and 600 mg/kg did not change leukocyte blood formula. At a dose of 1000 mg/kg CHSS caused the increase of percentage of banded neutrophils in males and females by 84,6% (p<0,05) and 87,5% (p<0,05), respectively. Also it was registered the increase in the percentage of basophils, in males it grew by 300% (p<0,05) and in females — by 85,7% (p<0,05), respectively. The percentage of lymphocytes decreased in males — by 12,8% (p<0,05), and females — 11% (p<0,05), respectively. Conclusions. As a result of research of global analysis of blood it was not discovered substantial changes in haematological parameters at introduction of CHSS in doses 200 and 600 mg/kg. However, it was found the development of intoxication and inflammation in the group of rats which were treated by CHSS in a dose 1000 mg/kg.

subacute toxicity, chondroitin sulfate sodium, global blood analysis, leukocyte formula

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«Bulletin of problems biology and medicine» Issue 1 part 1 (126), 2016 year, 84-87 pages, index UDK 615.9+616.12+616.72-002