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7. Induction of xenobiotic-metabolizing enzymes in hepatocytes by beta-naphthoflavone: Time-dependent changes in activities, protein and mRNA levels

Author

Lněničková Kateřina, Skálová Lenka, Stuchlíková Lucie, Szotáková Barbora, and Matoušková Petra

Subjects
aryl hydrocarbon receptor (ahr), beta-naphthoflavone, rat hepatocyte, time dependency, mrna-protein correlation, Pharmaceutical industry, HD9665-9675
Abstract

In the present study, time-dependency of the induction effect of a selective inducer on the activity, protein and mRNA levels of cytochromes P450 1A1/2 (CYP1A1/2), NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferases (GSTA), in primary culture of rat hepatocytes was tested and evaluated. To show the differences in responses of tested enzymes, the common aryl hydrocarbon receptor (AhR) ligand agonist, beta-naphthoflavone (BNF), was used. Induction of CYP1A1/2 by BNF was detected at all time intervals and at all levels (i.e., mRNA, protein, enzyme activity). Different responses of NQO1 and GSTA upon BNF treatment were observed. Our results demonstrate that the responses of different xenobiotic-metabolizing enzymes to the inducer vary in time and depend on the measured parameter. For these reasons, an induction study featuring only one-time interval treatment and/ or one parameter testing could produce misleading information.

Published
2018
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9. Effect of Green Tea Extract-Enriched Diets on Insulin and Leptin Levels, Oxidative Stress Parameters and Antioxidant Enzymes Activities in Obese Mice

Author

Bártíková Hana, Boušová Iva, Matoušková Petra, Szotáková Barbora, and Skálová Lenka

Subjects
monosodium glutamate-induced obesity, catechins, oxidative stress, polyphenon 60, Nutrition. Foods and food supply, TX341-641
Abstract

Green tea and green tea extracts (GTE) are often incorporated into diet intended to weight reduction, although the information about their efficacy in obese individuals is insufficient. The present study was designed to follow up the effect of defined and standardized GTE in mice with obesity induced by monosodium L-glutamate. Obese mice were fed with GTE-supplemented diet in three dosage regimens: 28-day and 3-day intake of 1 g GTE in 1 kg of diet and 28-day intake of 0.1 g GTE in 1 kg of diet. The information on body weight, food intake, oxidation stress parameters in blood and antioxidant enzymes activity in liver and small intestine was obtained. High doses of GTE decreased the specific activities of glutathione reductase and catalase and increased concentrations of malondialdehyde in blood. Specific activities of antioxidant enzymes in the liver and small intestine were not altered after GTE treatment except the decrease of NAD(P)H:quinone oxidoreductase activity. Our results showed that GTE did not affect average body weight and did not markedly improve antioxidant status in glutamate-induced obese mice. Moreover, intake of high doses of GTE made antioxidant defense in obese animals even worse.

Published
2017
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12. Effect of oral administration of green tea extract in various dosage schemes on oxidative stress status of mice in vivo

Author

Bártíková Hana, Skálová Lenka, Valentová Kateřina, Matoušková Petra, Szotáková Barbora, Martin Jan, Kvita Vojtěch, and Boušová Iva

Subjects
green tea extract, dietary supplement, flavonoids, green tea catechins, antioxidant enzymes, Pharmaceutical industry, HD9665-9675
Abstract

Green tea is a favorite beverage and its extracts are popular components of dietary supplements. The aim of the present in vivo study was to obtain detailed information about the effect of a standard green tea extract (Polyphenon, P), at different doses, on antioxidant enzymes and oxidative stress markers in murine blood, liver, small and large intestine. In all doses, P improved the oxidative stress status via an increased content of plasmatic SH-groups (by 21-67 %). Regarding antioxidant enzymes in tissues, the low dose of P had the best positive effect as it elevated the activity of NADPH quinone reductase in liver and small intestine, thioredoxin reductase in small intestine and hepatic superoxide dismutase. Based on these facts, consumption of green tea seems to be safe and beneficial, while consumption of dietary supplements containing high doses of catechins may disturb oxidative balance by lowering the activity of thioredoxin reductase, glutathione S-transferase, glutathione reductase and superoxide dismutase

Published
2015
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26. Ivermectin environmental impact: Excretion profile in sheep and phytotoxic effect in Sinapis alba

Author

Šadibolová Michaela, Lamka Jiří, Skálová Lenka, Sobotová Dominika, Lokvencová Kateřina, Szotáková Barbora, Ivan Vokřál, Prchal Lukáš, and Podlipná Radka

Subjects
Injections, Subcutaneous, Health, Toxicology and Mutagenesis, 0211 other engineering and technologies, Cmax, Sinapis, 02 engineering and technology, 010501 environmental sciences, Biology, Ecotoxicology, 01 natural sciences, Excretion, Feces, chemistry.chemical_compound, Animal science, Ivermectin, Pharmacokinetics, medicine, Animals, Avermectin, 0105 earth and related environmental sciences, Anthelmintics, 021110 strategic, defence & security studies, Sheep, urogenital system, Public Health, Environmental and Occupational Health, Area under the curve, General Medicine, Pollution, chemistry, Area Under Curve, embryonic structures, Toxicity, Cattle, Phytotoxicity, Environmental Pollution, medicine.drug
Abstract

Ivermectin (IVM), a macrocylic lactone from the avermectin family, is a potent broad-spectrum anthelmintic drug widely used in veterinary as well as human medicine. Although the health benefits of IVM treatment are particularly important, this drug also represents an environmental pollutant with potentially negative effects on many non-target species. To evaluate the ecotoxicological risk of IVM administration to livestock, information evaluating achievable environment-reaching concentration is needed. Therefore, the present study was designed to determine the excretion profile of subcutaneously administered IVM in sheep. The standard recommended dose of IVM (0.2 mg kg−1 b.w.) was used. UHPLC/MS/MS was used for the analysis of IVM faecal concentration. In addition, the effect of IVM on seed germination and early roots growth of white mustard (Sinapis alba L.) was evaluated in order to estimate the potential phytotoxic effect of IVM. Based on the obtained results, the parameters of IVM pharmacokinetics (maximum concentration (cmax), time to achieve maximum concentration (tmax), mean residence time (MRT), area under the curve (AUC)) were calculated. IVM elimination in sheep was slow, but faster than the elimination reported previously in cattle. Great interindividual differences were also observed. A two-peak profile of concentration curves indicate the importance of the active efflux of IVM via enterocytes. A “seed germination and early roots growth” test revealed significant IVM phytotoxicity (20% inhibition of root growth) even at 50 nM concentration, a level which may be found in the environment. This newly demonstrated phytotoxicity of IVM together with its well-known toxicity to invertebrates should be taken into account, and thus animals treated with IVM should not be kept in pastures, especially not in sites with high ecological value.

Published
2019

30. Pistacia lentiscus: From Phytopharmacology to Scientific Explanations on Its Anti-Inflammatory and Antimicrobial Capacity

Author

Milia, Egle, Bullitta, Simonetta, Mastandrea, Giorgio, Szotáková, Barbora, Schoubben, Aurelie, Langhansova, Lenka, Quartu, Marina, Bortone, Antonella, and Eick, Sigrun

Subjects
allergology
Abstract

There is an increasing interest in revisiting plants for drug discovery proving scientifically their role as remedies. Pistacia lentiscus (PL) is a wild-growing shrub rich in terpenoids, which are pharmacological appealing. The more recurrent components in the oil are represented by α-pinene, terpinene, caryophyllene, limonene, and myrcene. High concentration of polyphenols enriches the extracts. PL-extracts showed in vitro and in animal model strong anti-inflammatory and anti-oxidative activities. The anti-inflammatory activity mainly occurs due to inhibition of NF-kB pathway or directly toward the proinflammatory cytokines, or arachidonic acid cascade against COX-2 and LOX. The antimicrobial activity of PL essential oil and extracts includes among others Staphylococcus aureus, Escherichia coli, periodontal bacteria and Candida sp.. In conclusion, the biological properties, and particularly the anti-inflammatory and anti-microbial capacity, propose PL as a new safe pharmaceutical agent.

Published
2021

34. The Modulation of Phase II Drug-Metabolizing Enzymes in Proliferating and Differentiated CaCo-2 Cells by Hop-Derived Prenylflavonoids

Author

Lněničková, Kateřina, Šadibolová, Michaela, Matoušková, Petra, Szotáková, Barbora, Skálová, Lenka, and Boušová, Iva

Subjects
Flavonoids, Neoprene, Propiophenones, catechol-O-methyltransferase, enzymatic activity, Gene Expression, mRNA expression, Cell Differentiation, lcsh:TX341-641, sulfotransferase, Catechol O-Methyltransferase, Article, CaCo-2 cells, xanthohumol, prenylflavonoid, UDP-glucuronosyl transferase, Humans, Glucuronosyltransferase, Sulfotransferases, Humulus, lcsh:Nutrition. Foods and food supply, Cell Proliferation, Glutathione Transferase, glutathione S-transferase
Abstract

Prenylflavonoids in the human organism exhibit various health-beneficial activities, although they may interfere with drugs via the modulation of the expression and/or activity of drug-metabolizing enzymes. As intestinal cells are exposed to the highest concentrations of prenylflavonoids, we decided to study the cytotoxicity and modulatory effects of the four main hop-derived prenylflavonoids on the activities and mRNA expression of the main drug-conjugating enzymes in human CaCo-2 cells. Proliferating CaCo-2 cells were used for these purposes as a model of colorectal cancer cells, and differentiated CaCo-2 cells were used as an enterocyte-like model. All the tested prenylflavonoids inhibited the CaCo-2 cells proliferation, with xanthohumol proving the most effective (IC50 8.5 &micro, M). The prenylflavonoids modulated the activities and expressions of the studied enzymes to a greater extent in the differentiated, as opposed to the proliferating, CaCo-2 cells. In the differentiated cells, all the prenylflavonoids caused a marked increase in glutathione S-transferase and catechol-O-methyltransferase activities, while the activity of sulfotransferase was significantly inhibited. Moreover, the prenylflavonoids upregulated the mRNA expression of uridine diphosphate (UDP)-glucuronosyl transferase 1A6 and downregulated that of glutathione S-transferase 1A1/2.

Published
2020

38. Základní biochemické dráhy v buňce

Author

Skálová, Lenka, Szotáková, Barbora, Netopilová, Miloslava, Skálová, Lenka, Szotáková, Barbora, and Netopilová, Miloslava

Abstract

Čtvrté vydání učebního textu pro posluchače Farmaceutické fakulty UK. Text doplňuje přednášku z obecné biochemie. Obsah: metabolismus sacharidů, citrátový cyklus a dýchací řetězec, fotosyntéza, metabolismus lipidů, metabolismus aminokyselin a dusíkatých látek, metabolismus porfyrinů, buněčná signalizace přes membránové receptory.

Published
2022

45. The Pharmaceutical Ability of Pistacia lentiscus L. Leaves Essential Oil Against Periodontal Bacteria and Candida sp. and Its Anti-Inflammatory Potential

Author

Milia, Egle, primary, Usai, Marianna, additional, Szotáková, Barbora, additional, Elstnerová, Marie, additional, Králová, Věra, additional, D’hallewin, Guy, additional, Spissu, Ylenia, additional, Barberis, Antonio, additional, Marchetti, Mauro, additional, Bortone, Antonella, additional, Campanella, Vincenzo, additional, Mastandrea, Giorgio, additional, Langhansová, Lenka, additional, and Eick, Sigrun, additional

Published
2020
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