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RESEARCH OF SUBCHRONIC TOXICITY OF BENZOFURAN DERIVATIVES

Keywords:

L.G. Gorokhova, N.N. Mihailova


Amiodaron production (antiarrhythmics of class III) is characterized by formation of some semi-products: such benzofuran derivatives as 2-butirilbenzofuran, 2-butil-3(4-oxybenzoil) benzofuran, (2-butil-3-benzofuranil)-(4-oxy-3.5-diiodfenil)metanon. Possible contact of large number of people with the given semiproducts was the basis for carrying out the present work. Its aim was experi-mental study on the effect of amiodaron and semiproducts of its synthesis on an organism at subacute intragastric introduction. For the estimation of toxic action of substances studied subchronic experiment was conducted, everyone toxicant was introduced to rats in the number of 0.1 DL50 in the form of oil solution within 4 weeks. An the end of the 2-th and 4-th weeks of priming biochemical research of blood serum was carried out by the following indices: activity of АSТ, АLТ, alkaline phosphatese, cholinesterase, α-amylase; concentration of crude protein, urea, and cholesterol and chlorine ions. At the priming end fragments of heart, lungs, liver, kidneys, stomach, and spleen were got for histological research. When priming with 2-butirilbenzofuran the increase in the activity of alkaline phosphatese and АLТ, the decrease in the concentration of urea and cholesterol increase were revealed. The tendency to the decrease in cholinesterase activity was observed. In introduction of 2-butil-3(4-oxybenzoil)benzofuran within 4 weeks the increase in urea concentration was observed only. Fortnight introduction of (2-butil-3-benzofuranil)-(4-oxy-3.5-diiodfenil)metanon caused the increase in the activity of АLТ, alkaline phosphatese, and the decrease in cholesterol and urea con-centrations. The priming with amiodaron had led to the change of the majority of parameters in-vestigated: the increase in the activity of АSТ and АLТ, the increase in urea concentration were marked. The tendency to the increase in the activity of alkaline phosphatese and the increase in cholesterol concentration was observed. The results received evidence the greatest degree of ami-odaron toxicity in comparison with other benzofuran studied. Histological researches had shown the pathmorphologic changes of organs and tissues of different degree of manifestation: vivid ex-pression of dystrophic hepatocytes changes, partial necronephros. Thus, during the experiment it had been found out the substances depending on a chemical structure and priming terms render hepatotoxic and nephrotoxic effect of various severity. Long-term benzofuran introduction to a worker’s organism even in small doses can cause clinically sig-nificant irreversible damages of liver and kidneys. Therefore it is necessary to minimize contact with the given substances at the pharmaceutical industry enterprises.
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