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Study of the mechanisms of action of phenolic compounds on vascular smooth muscle
Alves Dias, Patrícia Alexandra ; Mladěnka, Přemysl (advisor) ; Kyselovič, Ján (referee) ; Štengl, Milan (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Training Workplace Department of Pharmacology and Toxicology Doctoral Degree Program Pharmacology and Toxicology Candidate Patrícia Alexandra Alves Dias, M.Sc. Supervisor prof. Přemysl Mladěnka, Pharm.D., Ph.D. Advisor assoc. prof. Jana Pourová, Pharm.D., Ph.D. Title of Doctoral Thesis Study of the mechanisms of action of phenolic compounds on the vascular smooth muscle Cardiovascular diseases including hypertension, coronary artery disease, peripheral artery disease, and cerebrovascular disease remain the leading cause of death worldwide. In addition, discouraging estimations have suggested a future increase in the number of cardiovascular patients. Thus, novel treatment modalities are clearly needed to prevent or reverse these epidemic trends. Phenolic compounds contain one or more hydroxyl groups bound to a benzene ring. This class of chemicals includes: a) natural compounds (e.g., dietary polyphenols and small phenolic metabolites) referred to as nutraceuticals due to their claimed health-promoting effects and b) synthetic compounds (e.g., bisphenols) which, on the contrary, have been suggested to negatively affect human health. Even if there are claims that polyphenol-rich diet is associated with cardioprotective effects, important...
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Vliv chronické expozice chloridazonu a jeho metabolitu chloridazon desphenylu na raka signálního
MATERNA, Jan
The aim of this thesis was to evaluate the effect of chloridazon (Ch) and its major metabolite chloridazon desphenyl (Ch-D) at environmentally relevant concentrations 0.45 micrograms/l (Ch1; Ch-D1) and 2.7 micrograms/l (Ch2; Ch-D2) on adult signal crayfish (Pacifastacus leniusculus). The exposure was 30-day and followed by a 15-day depuration period. The effect of the tested substances was evaluated on the basis of behavior, biochemical profile of hemolymph, biomarker of oxidative stress and antioxidants parameters. The tested substances did not effect on the behavior of crayfish. Chloridazone at concentration 2.7 micrograms/l (Ch2) caused a significant (P<0.01) increase of glucose (GLU), lactate (LACT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in haemolymph of crayfish and changes in catalase (CAT) levels in the gills and the hepatopancreas, compared to controls. Crayfish exposed to chloridazon in both tested concentrations (0.45 micrograms/l and 2.7 micrograms/l) showed significantly (P<0.01) higher level of reduced glutathione (GSH) in hepatopancreas and gills compared to control. Exposure of chloridazon desphenyl at concentration 0.45 micrograms/l and 2.7 micrograms/l caused significantly (P<0.01) higher levels of glucose, lactate, ammonia (NH3), calcium (Ca), alanine aminotransferase and aspartate aminotransferase activity in haemolymph of exposed crayfish compared to control. Chloridazon desphenyl in both tested concentrations caused significant (P<0.01) changes in the levels of lipid peroxidation (LPO) in the hepatopancreas and catalase (CAT) and GSH level in the gills and hepatopancreas compared to the control group. Some effects persist after a depuration period. The results showed that the metabolite chloridazon desphenyl has more pronounced effects on the physiology of adult signal crayfish than its parent compound chloridazon. It can be stated, that chloridazon and its metabolite chloridazon desphenyl has the strongly negative and harmful effects of on crayfish as representatives of non-target aquatic organisms.
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