Budou analyzovány vztahy mezi komponentami metabolického syndromu a depresí, složením diety, koncentracemi PUFA v lipidech plazmy, homocysteinu, ukazateli oxidačního stresu a zánětu, vybranými cytokiny a mozkovým neurotrofickým faktorem v séru Bude testována hypotéza o kauzálním vztahu mezi deficiencí PUFA n-3, zvýšenou koncentrací homocysteinu, oxidačním stresem při rozvoji metabolického syndromu a deprese a vlivu vybraných genetických polymorfizmů na tyto vztahy.; The interactions between components of metabolic syndrome and depression, dietary pattern, profiles of PUFA in plasma lipids, homocysteine, parameters of oxidative stress as well as inflammation, selected cytokines and BDNF in serum will be analysed. Thehypothesis about the causal relation between the deficiency of PUFA n-3, high homocysteine, oxidative stress in development of metabolic syndrome and depression and effect of selected genetic polymorphisms on these relations will be tested.

• MeSH
• depresivní poruchy genetika   metabolismus   MeSH
• homocystein MeSH
• metabolický syndrom genetika   metabolismus   MeSH
• omega-3 mastné kyseliny genetika   metabolismus   MeSH
• oxidační stres MeSH
• polymorfismus genetický MeSH
• receptor trkB MeSH
• zánět MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• vnitřní lékařství
• biologie
• psychiatrie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

Tissue ischemia is connected with the production of free radicals (FR). This study was designed to directly measure of the amount of FR in rat brains related to a photothrombotic ischemic event shortly after establishing the lesion. A model of left hemisphere photothrombosis ischemia was used in the experiment. Brains of animals from the experimental group were removed and placed in liquid N(2) for 60 min after the green laser exposure, the control group brains, exposed to the photosensitive dye Rose Bengal (RB), were placed in liquid N(2) for 80 min after RB application, naive control brains were also briefly stored in liquid N(2). Spectroscopy of electron paramagnetic (spin) resonance was used to directly measure FR (hydroxyl (OH(.)) and nitroxyl (NO(.)). Compared to naive controls, both the ischemia and RB groups had significantly higher levels of OH(.), however, there were no differences between them. Comparison of hemispheres, i.e., with and without ischemia, in the experimental group did not show any significant difference in OH(.). NO(.) were elevated in the ischemia and RB groups compare to naive controls. Higher levels of NO(.) were found in hemispheres with ischemia compared to unexposed hemispheres. Increases in OH(.) were probably associated with the action of RB itself in this model of ischemia. Increases in NO(.) were closely related to the pathogenesis of photothrombotic ischemia and could be related to the activity of nitric oxide synthases.

• MeSH
• elektronová paramagnetická rezonance MeSH
• hydroxylový radikál metabolismus   MeSH
• ischemie mozku metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• mozková kůra krevní zásobení   MeSH
• oxidy dusíku metabolismus   MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

An epileptic seizure and postictal period in addition to well-known features are also characterized by massive consumption of energy. This is thought to lead to oxidative stress and increased generation of free radicals, which is reflected by increased levels of oxidative products. Our previous work described the neuroprotective effects of melatonin in preventing cognitive worsening after a single epileptic seizure. This work was aimed on direct measurement of free radicals in brain tissue using the EPR method 1, 15 and 60 minutes after seizure. The measurement was performed in adult male Wistar rats at the mentioned intervals after a single tonic-clonic seizure induced by flurothyl. In comparison to control animals there was a significant increase in hydroxyl and nitroxyl radicals 60 minutes after the seizure. The levels of hydroxyl radicals were significantly lower in animals that received melatonin 60 minutes before seizure induction compared to animals without preventive treatment. Therefore, melatonin affected the generation of the measured free radicals differently. An important finding was the delayed increase in free radicals after a single seizure in the later phases of recovery.

• MeSH
• antioxidancia aplikace a dávkování   MeSH
• epilepsie farmakoterapie   metabolismus   MeSH
• hydroxylový radikál metabolismus   MeSH
• krysa rodu rattus MeSH
• látky tlumící činnost CNS aplikace a dávkování   MeSH
• melatonin aplikace a dávkování   MeSH
• oxidační stres účinky léků   MeSH
• oxidy dusíku metabolismus   MeSH
• potkani Wistar MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Doxorubicin belongs to anthracycline cytotoxic drugs and it is widely used as a major therapeutic agent in the treatment of various types of tumors. However,its therapeutic use is limited by the development of myelosuppression and cardiotoxicity after a specific cumulative dose is reached. The aim of this study was to investigate the effect of flavonoids, either natural or synthetic on doxorubicin-mediated formation of oxidative stress implicated in doxorubicin toxicity. Doxorubicin caused a concentration-dependent increase in the formation of hydroxyl radicals in minipig liver microsomes used as an in-vitro model system. When bacterial membranes heterologously expressing human NADPH cytochrome-P450 oxidoreductase were incubated with doxorubicin, formation of the superoxide radical under aerobic conditions and the doxorubicin–semiquinone radical under anaerobic conditions was detected. Forty different flavonoids were tested for their potency to prevent NADPH-induced or Fe2+-induced peroxidation of lipids in the microsomal system. According to the results, seven flavonoids were selected for evaluation of their potency to inhibit doxorubicin-dependent formation of hydroxyl radicals assessed by electron spin resonance. Myricetin, fisetin, and kaempferol were found to produce a significant protective effect against hydroxyl radicals in the minipig liver microsomal system. In conclusion, this study shows the use of a novel cost-effective in-vitro model system for preselection of antioxidants for testing of their protective effects against toxicity of anthracyclines and potentially other oxidative stress-inducing chemicals.

• MeSH
• benzochinony metabolismus   MeSH
• doxorubicin farmakologie   toxicita   MeSH
• elektronová paramagnetická rezonance MeSH
• flavonoidy farmakologie   MeSH
• hydroxylový radikál metabolismus   MeSH
• jaterní mikrozomy účinky léků   metabolismus   MeSH
• lidé MeSH
• modely u zvířat MeSH
• NADPH-cytochrom c-reduktasa metabolismus   MeSH
• oxidační stres účinky léků   MeSH
• peroxidace lipidů účinky léků   MeSH
• prasata MeSH
• protinádorová antibiotika farmakologie   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• superoxidy metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Increasing attention has been paid to clinical manifestation of oxidative stress and reactive oxygen and nitrogen species (RONS), e.g. in atherosclerosis, diabetes mellitus, hyperlipidemia, neurodegenerative and psychiatric diseases. The most clinically significant RONS are free radicals (superoxide anion, hydroxyl and nitroxide radicals) and non-radical species (peroxynitrite, hydrogen peroxide). The aim of this study was to investigate by EPR the concentrations of hydroxyl and nitroxide radicals in blood serum of patients with hyperlipidemia and with depressions and to compare them with healthy persons. Nitroxide radical concentrations were significantly higher in the depressive patients compared with controls. The clinical significance of this finding is not quite clear, but it supports the hypothesis on the participation of oxidative stress in pathogenesis of depressive disorders.

• MeSH
• deprese krev   MeSH
• elektronová paramagnetická rezonance metody   MeSH
• financování organizované MeSH
• hyperlipidemie krev   MeSH
• oxidační stres MeSH
• reaktivní formy dusíku analýza   MeSH
• reaktivní formy kyslíku analýza   MeSH
• volné radikály analýza   MeSH

This study investigated the effect of naturally occurring flavonoids and synthetic aurone derivatives on the formation of cardiotoxic doxorubicinol and transport of doxorubicin in breast cancer cells. Quercetin significantly inhibited the formation of doxorubicinol. Quercetin and aurones did not significantly affect transport of [14C]doxorubicin in human resistant breast cancer cells. In conclusion, quercetin should be further tested for its potency to decrease doxorubicin-mediated toxicity.

• MeSH
• benzofurany farmakologie   MeSH
• biologický transport účinky léků   MeSH
• doxorubicin analogy a deriváty   farmakokinetika   metabolismus   MeSH
• financování organizované MeSH
• flavonoidy farmakologie   MeSH
• lidé MeSH
• metabolismus účinky léků   MeSH
• nádorové buněčné linie MeSH
• nádory prsu MeSH
• protinádorová antibiotika MeSH
• quercetin farmakologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH

OBJECTIVES: The aim of the study was to demonstrate the ability to measure free radicals and singlet oxygen, using EPR methods, in the tail of anaesthetized rats. The advantage of this method lies in the potential for continuous evaluation of free radicals and singlet oxygen during nociceptive processes.

• MeSH
• antioxidancia farmakologie   MeSH
• bolest metabolismus   MeSH
• elektronová paramagnetická rezonance veterinární   MeSH
• financování organizované MeSH
• hydroxylový radikál analýza   metabolismus   MeSH
• krysa rodu rattus MeSH
• měření bolesti metody   přístrojové vybavení   MeSH
• ocas metabolismus   MeSH
• oxidy dusíku analýza   metabolismus   MeSH
• potkani Wistar MeSH
• práh bolesti fyziologie   účinky léků   MeSH
• singletový kyslík analýza   metabolismus   MeSH
• volné radikály analýza   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

• Publikační typ
• abstrakty MeSH

• MeSH
• antioxidancia MeSH
• oxidace-redukce MeSH
• oxidační stres MeSH
• patologické procesy MeSH
• singletový kyslík fyziologie   chemie   metabolismus   MeSH

Reactive metabolites of benzene 1,4-benzoquinone and 1,4-hydroquinone exert their toxic effects through covalent and/or oxidative damage to DNA and proteins. Since minipigs have been proposed as a suitable model species in toxicological and pharmacological research, the aim of this study was to explore mechanisms by which catechol, 1,4-hydroquinone and 1,4-benzoquinone destroy cytochrome P450 (P450) and induce oxidative stress in minipig liver microsomes. Our second goal was to assess the usefulness of minipig liver microsomes as a model system for the testing of the production of oxidative stress by clinically relevant quinone-containing compounds, e.g. anthracyclines. Of the three benzene metabolites tested, the highest P450 destruction was caused by 1,4-benzoquinone. This destructive effect did not correlate with the production of hydroxyl radicals as measured by ESR spin trapping which was the highest in samples containing 1,4-hydroquinone. Our results confirm previous findings that 1,4-benzoquinone exerts its effect mainly by direct attack on macromolecules while 1,4-hydroquinone rather stimulates the production of reactive oxygen species. Doxorubicin stimulated the production of hydroxyl radicals and the destruction of P450 similarly as 1,4-hydroquinone. Minipig liver microsomes should be further tested as a possibly suitable model system for the testing of potential modulators of the toxicity of doxorubicin.

• MeSH
• algoritmy MeSH
• benzen MeSH
• benzochinony metabolismus   toxicita   MeSH
• cytochrom P-450 CYP2E1 metabolismus   MeSH
• cytochrom P-450 CYP3A metabolismus   MeSH
• doxorubicin toxicita   MeSH
• elektroforéza v polyakrylamidovém gelu MeSH
• elektronová paramagnetická rezonance MeSH
• financování organizované MeSH
• hydrochinony metabolismus   toxicita   MeSH
• hydroxylový radikál metabolismus   MeSH
• inhibitory cytochromu P450 MeSH
• jaterní mikrozomy metabolismus   účinky léků   MeSH
• miniaturní prasata metabolismus   MeSH
• NADP toxicita   MeSH
• orchiektomie MeSH
• oxidační stres účinky léků   MeSH
• peroxidace lipidů účinky léků   MeSH
• prasata MeSH
• protinádorové antimetabolity toxicita   MeSH
• systém (enzymů) cytochromů P-450 MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH