Registration Number
0213U003653,
0110U001219
, R & D reports
Title
Mechanisms of hepato- and gonadotoxic effects of antituberculosis drugs mediated by their biotransformation in the organism (an experimental study)
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Head
Kovalenko Valentina Mikolaivna, Доктор біологічних наук
Registration Date
28-02-2013
Organization
State Establishment "Institute of Pharmacology and Toxicology National Academy of Medical Science of Ukraine"
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Mechanisms of hepato-and gonadotoxic effects of antituberculosis drugs were the object of study. Determination of the role of cytochrome P-450 - 2E1, 3A4, 2C19 isoforms in the mechanism of hepato- and gonadotoxic effects of anti-tuberculosis drugs combination, as well as approaches to the pharmacocorection of their side effects in the experiment were the purpose. Objectives of the study: a comparative study of cytochrome P-450 isoforms genes expression, biochemical, morphological and functional abnormalities in the liver and gonads of male rats following intragastric separate and co-administration of isoniazid, rifampicin, pyrazinamide, and ethambutol or streptomycin, and identification of corrective action of methionine and experimental composition "Metovitan." Methods: toxicological, biochemical, molecular, morphological, statistical. Results of the study suggest that replacing of ethambutol to streptomycin in antituberculosis drugs combination reduced the degree of hepato-and gonadotoxic effects. Therapeutic and prophylactic administration of methionine or experimental composition "Metovitan" (to ensure optimal conditions of methylation in the organism) in male rats corrected expression of cytochrome 2E1, 3A2 and 2C23 in the liver. That was associated with decreased symptoms of hepatotoxicity. Also, under these conditions we showed normalization of the cytochrome P-450 isoforms expression in the testes and decrease of lipid peroxidation processes activity in the gonads, which improved fertility of male rats.
Product Description
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Анісімова Світлана Ігорівна
Блажчук Ірина Степанівна
Бондаренко Лариса Борисівна
Волошина Олена Семенівна
Вороніна Алла Костянтинівна
Карацуба Тетяна Володимирівна
Кравченко Тамара Григорівна
Мазаманян Ганна Миколаївна
Матвієнко Анатолій Васильович
Морозович Юлія Анатоліївна
Покровська Світлана Володимирівна
Смирнова Ганна Іванівна
Таніна Сусана Салтанатівна
Чорна Євгенія Григорівна
Шаяхметова Ганна Михайлівна
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2020-04-02