Search academic texts

Information × Registration Number 0216U001775, 0113U000739 , R & D reports Title Cytochrome P-450 isoforms in mechanisms of interactions of drugs for metabolic syndrome correction at pubertal and adult male rats popup.stage_title Head Kovalenko Valentina Mykolayvna, Доктор біологічних наук Registration Date 18-04-2016 Organization State Establishment "Institute of Pharmacology and Toxicology National Academy of Medical Science of Ukraine" popup.description2 ABSTRACT Report: 164 pp., 49 fig., 20 tab., 2 app 142 sources. Object of research - age specificity of drugs metabolіzm with the participation of cytochrome P-450 (CYP450). Purpose - to explore the functioning of the CYP450 (CYP3A, CYP2S and CYP2E1) in pubertal and adult male rats with the metabolic syndrome for predicting the interactions of drugs used in this disease in adolescents and adults. Research Methods - toxicological, pharmacological, biochemical, molecular biological, morphological, statistical. For the first time it was found that the development of the metabolic syndrome is accompanied by a decrease of mRNA expression intensity of CYP2S23 (CYP2C9 and CYP2C19 ortholog) in the liver of adult rats and pubertal animals. Unlike adult animals pubertals had increased levels of CYP2E1 and CYP3A2 (ortholog of CYP3A4) mRNA expression, respectively 80% and 40% compared with the control. Losartan and metformin administered to pubertal rats with metabolic syndrome, caused a 2.5-fold increase in expression of the gene CYP2C23 compared to animals treated with losartan alone. In adult rats, the simultaneous administration of drugs had no effect on the expression of isoforms of CYP450. It was shown that in puberty the organism with metabolic syndrome had a more profound violations of pro / antioxidant status (compared with adult animals). Comparative analysis of serum ratio LDL / HDL and the relative weight of abdominal fat with metabolic syndrome indicated higher adaptation and compensatory possibilities of pubertal rats (relative to the lipid metabolism) compared to adult animals. Data on the characteristics of violations of gene expression of cytochromes involved in the biotransformation of the majority of drugs (ortholog of CYP2C9 and CYP2C19, CYP2E1, ortholog of CYP3A4) in the liver of the pubertal rat with metabolic syndrome and the use of model drugs (metformin and losartan) should be taken into account in pharmacotherapy of adolescents with metabolic syndrome , when using drugs which are metabolized with the relevant CYP450 isoforms, due to the risk of increasing toxicity and reducing efficacy. Results of the research are introduced in the form of the Information letter №31, 2014 "Criteria indicators of experimental metabolic syndrome in puberty." Forward-looking assumptions on object of the study - long-term consequences of age-related characteristics of drug metabolism. CYP2E1, CYP3A2, CYP2C23. Product Description popup.authors Блажчук І.С. Бондаренко Л.Б. Вороніна А.К. Карацуба Т.А. Колядич О. Кравченко Т.Г. Мазманян Г.М. Матвієнко А.В. Рогозін В.В. Шаяхметова Г.М. popup.nrat_date 2020-04-02 Close