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Distribuce vybraných léčiv mezi články potravního řetězce ve vodním prostředí
LEXOVÁ, Veronika
This bachelor thesis deals with occurrence of pharmaceuticals in aquatic organisms. Sources of pharmaceuticals in recipients are treated effluents from sewage treatment plants. The mostly found in surface water and aquatic organisms are antibiotics, psychoactive pharmaceuticals, antihistamines, painkillers and cardiovascular pharmaceuticals. The occurrence of 20 selected pharmaceuticals at 10 localities affected by treated effluents from sewage treatment plants was studied in several types of matrices, in juvenile fish, plasma and muscle of adult common chub (Squalius cephalus), zebra mussel (Dreissena polymorpha) and benthic organisms. Based on the results, the highest concentrations of pharmaceuticals were found in benthic organisms and zebra mussels. The highest number of pharmaceuticals was found in benthic organisms (18 of 20 analysed) and 3 pharmaceuticals were found at all localities. The lowest number of pharmaceuticals was found in plasma and muscle of adult fish. Bílina Ústí nad Labem and Svratka Židlochovice belong to the most polluted localities. These rivers have low flows and treated wastewater from sewage treatment plants are less diluted therefore the concentration of pharmaceuticals in aquatic organisms is higher.
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Vliv vybraných kardiovaskulárních léčiv nalézaných ve vodním prostředí na ryby
STEINBACH, Christoph Antonius
Cardiovascular pharmaceuticals are among the most prescribed drugs. As a result of the high consumption, these pharmaceuticals have been frequently detected in waste and surface waters. Verapamil, diltiazem and atenolol are very important representatives of cardiovascular pharmaceuticals; therefore, the present research focused on their acute and sub-chronic effects, bioconcentration, half-life time and metabolism in fish. Moreover, unified protocol for the quantitative assessment of histopathological alterations on the heart ventricle and coronary blood vessels employing heart index calculation was developed with the aim to better assess histopathological changes in fish heart which is one of the targets of cardiovascular pharmaceuticals and other chemicals. The effects caused by high concentrations of the studied substances, verapamil, diltiazem and atenolol, in fish can be considered similar to the therapeutic effects and side effects that are found in humans. The acute exposure to verapamil at the human therapeutic plasma level reduced the heart rate in common carp embryos and larvae. In addition, the acute and chronic exposure to this substance caused peripheral edema and gastrointestinal haemorrhage in carp. Similarly, the histological changes in heart and the blood vessels of the liver in diltiazem exposed rainbow trout suggested vasodilatation similar to the pharmacological effect of diltiazem in the human body. In rainbow trout sub-chronically exposed to atenolol at a human therapeutic blood plasma concentration, histopathological changes in the cardiovascular system were found. The bioconcentration of verapamil, diltiazem and atenolol in fish can be classified as low. Bioconcentration factor (BCF) of verapamil in whole body homogenates of common carp ranged between 6.6 and 16.6. The BCF of diltiazem was also relatively low (0.5-194) in analysed tissues of trout, following the order kidney liver muscle blood plasma. BCF of atenolol in rainbow trout tissues was the lowest among the tested substances (BCF = 0.002-0.27), following the order of liver > kidney > muscle. In the blood plasma, the concentration of atenolol was below the limit of quantification. Verapamil showed a longer half-life time (10.6 days) in fish compared to the human body, indicating the slow rate of biotransformation and/or elimination of verapamil in fish. Estimated half-life times of diltiazem in liver (1.5 h) and kidney (6.2 h) were in the same order of magnitudes as those determined for the human blood plasma. The half-life time of atenolol in trout was not studied, because of its very low bioconcentration. In diltiazem exposed rainbow trout, 8 groups of metabolites of diltiazem with 17 different isoforms were identified using liquid chromatography/high resolution mass spectrometry method. Diltiazem was found to undergo a biotransformation involving desmethylation, desacethylation and hydroxylation in fish. These results showed that diltiazem was metabolised in fish in a similar way like in the human body by desmethylation and desacethylation. On the other hand, hydroxylation, which was involved to a minor extent, seemed to be species specific. Verapamil had no effect on early life stages of common carp at the environmentally relevant concentration after one month lasting exposure. On the other hand, atenolol and diltiazem in environmentally realistic concentrations caused after 42-day exposure some physiological changes in rainbow trout. Namely, atenolol affected haematological and biochemical parameters of the blood in exposed rainbow trout and diltiazem caused changes in the activity of antioxidant enzymes in trout liver and gills. These data indicated that atenolol and diltiazem, when present in the aquatic environment, could be a source of sub-lethal detrimental effects in fish.
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Occurence of beta-blockers and calcium channel blockers in aquatic environment and their influence on fish
BERANOVÁ, Petra
The aim of this bachelor thesis was to make an overview of distribution of beta-blockers and calcium channel blockers, their occurrence in aquatic environment and their impact on fish. Analysis of data obtained from the website of the State Instiute for Drug Control, which was carried out in Excel revealed, that 53 643 kilograms of beta-blockers and 24 472 kilograms of calcium channel blockers was distributed in the Czech Republic in 2011. Metoprolol, acebutlol and atenolol reached the largem volume of distribution among aktive ingredients in the group of beta-blockers. Verapamil, amlodipin and diltiazem were TOP 3 calcium channel blockers. These drugs are generally the most sold in the world and they can be found in surface waters in the Czech Republic and worldwide at concentrations rating from tens to hundreds ng.l-1 . The reason for this is the low removal rate of beta-blockers and calcium channel blockers in wastewater treatment plants, which ranges from 11 to 76%. Toxicity tests on fish with metoprolol, propranolol, atenolol, verapamil and diltiazem have shown the effect of this pharmaceuticals on e.g., reduction of fecundity, hatchability or heart rate. Various histopatological changes on the liver and heart or malformations of early developmental stages of fis have been also reported. The lowest concentrations of the tested substances at which these effects were observed, ranged mostly from values g.l-1 to mg.l-1, i.e. these concentrations were higher than those commonly found in surface waters. However, some effects were observed also at environmentally relevant concentrations. Due to prolong-term exposure on the organisms beta-blockers and calcium channel blockers may represent a threat to aquatic ecosystems. A solution could be to improve the mechanism for removal of pharmaceuticals in the sewage treatment plants.
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