THE COMPARATIVE EXPERIMENTAL TOXICOLOGICAL STUDY OF THE COMBINED ANTI-TUBERCULOSIS DRUG CONTAINING AND NOT CONTAINING PYRIDOXINE HYDROCHLORIDE

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Issue: 
4
Year: 
2017

K.I. Usov
Ph.D. (Biol.), Associate Professor, Head of Laboratory of Toxicology Tests and Researches Studies,
Test Laboratory Center, Research Institute of Biophysics, Angarsk State Technical University;
Chair of Pharmacology, Irkutsk State Medical University
E-mail: konstausov@yandex.ru
T.A. Guskova
Dr.Sc. (Med.), Professor, Non-profit Partnership of Assistance to Health Care «Scientific center of quality control» (Moscow)
G.G. Yushkov
Ph.D. (Med.), Research Scientist, Laboratory of Toxicology Tests and Researches Studies,
Test Laboratory Center, Research Institute of Biophysics, Angarsk State Technical University
A.V. Mashanov
Ph.D. (Biol.), Research Scientist, Laboratory of Toxicology Tests and Researches Studies,
Test Laboratory Center, Research Institute of Biophysics, Angarsk State Technical University

The aim of this work was to evaluate the role of pyridoxine hydrochloride in the reduction of toxicity in acute poisoning modern combined antituberculosis drug containing (drug «Protub-4 plus») and not containing pyridoxine hydrochloride (preparation «Protub-4»). Materials and methods. As experimental biological models mature white nonlinear rats (males, females) were selected. All animals were kept in a specialized experimental-biological clinics (vivarium). The parameters of acute toxicity of antituberculosis drugs established. The visually assessed behavior of rats was determined at the time of latent period (time before the onset of seizures), symptoms of epistatus and time spent by rats in a coma. The average life expectancy of dead rats, the levels of hematological and biochemical parameters of blood were established. The results of the study. The obtained data show the effect of the pyridoxine hydrochloride on neurotoxicity, manifested in the reduction of the duration of Epictetus, the time spent animals in a coma, but in General – the increase in lifespan when administered orally to rats, a median lethal dose of a combination drug «Protub-4 plus» compared to a combined preparation «Protub-4», not containing the pyridoxine hydrochloride. The pyridoxine hydrochloride in the drug «Protub-4 plus» had an impact on integral measures of the body condition of animals: body weight, consumption and allocation of water, the rate of exchange – xanturenic acid as a biomarker of altered metabolism of tryptophan and does not have a significant effect on hematological and biochemical blood parameters in comparison with the similar indicators with the introduction of the drug «Protub-4» animals. Conclusion. The conducted studies are mainly of experimental toxicological importance, but the findings can be used in the formation of rational programs of antituberculosis chemotherapy of tuberculosis in the direction of the preparation containing the pyridoxine hydrochloride.

Keywords: 
Key words: acute toxicity
median lethal dose
combined antituberculosis drugs
isoniazid
pyrazinamide
rifampicin
ethambutol
rational chemotherapy
pyridoxine hydrochloride
vitamin B6
experimental studies.

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