The identification and quantification of mitochondrial effects of novel antipsychotics (brexpiprazole, cariprazine, loxapine, and lurasidone) were studied in vitro in pig brain mitochondria. Selected parameters of mitochondrial metabolism, electron transport chain (ETC) complexes, citrate synthase (CS), malate dehydrogenase (MDH), monoamine oxidase (MAO), mitochondrial respiration, and total ATP and reactive oxygen species (ROS) production were evaluated and associated with possible adverse effects of drugs. All tested antipsychotics decreased the ETC activities (except for complex IV, which increased in activity after brexpiprazole and loxapine addition). Both complex I- and complex II-linked respiration were dose-dependently inhibited, and significant correlations were found between complex I-linked respiration and both complex I activity (positive correlation) and complex IV activity (negative correlation). All drugs significantly decreased mitochondrial ATP production at higher concentrations. Hydrogen peroxide production was significantly increased at 10 µM brexpiprazole and lurasidone and at 100 µM cariprazine and loxapine. All antipsychotics acted as partial inhibitors of MAO-A, brexpiprazole and loxapine partially inhibited MAO-B. Based on our results, novel antipsychotics probably lacked oxygen uncoupling properties. The mitochondrial effects of novel antipsychotics might contribute on their adverse effects, which are mostly related to decreased ATP production and increased ROS production, while MAO-A inhibition might contribute to their antidepressant effect, and brexpiprazole- and loxapine-induced MAO-B inhibition might likely promote neuroplasticity and neuroprotection. The assessment of drug-induced mitochondrial dysfunctions is important in development of new drugs as well as in the understanding of molecular mechanism of adverse or side drug effects.

• Klíčová slova
• ATP, Dopamine system stabilizers, Mitochondrial respiration, Monoamine oxidase, Oxidative phosphorylation, Reactive oxygen species,
• MeSH
• adenosintrifosfát biosyntéza   MeSH
• antipsychotika klasifikace   farmakologie   MeSH
• chinolony farmakologie   MeSH
• elektronový transportní řetězec účinky léků   MeSH
• energetický metabolismus účinky léků   MeSH
• inhibitory MAO farmakologie   MeSH
• loxapin farmakologie   MeSH
• lurasidon hydrochlorid farmakologie   MeSH
• mitochondrie účinky léků   metabolismus   MeSH
• peroxid vodíku metabolismus   MeSH
• piperaziny farmakologie   MeSH
• prasata MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• receptory neurotransmiterů účinky léků   MeSH
• spotřeba kyslíku účinky léků   MeSH
• thiofeny farmakologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adenosintrifosfát MeSH
• antipsychotika MeSH
• brexpiprazole MeSH Prohlížeč
• cariprazine MeSH Prohlížeč
• chinolony MeSH
• elektronový transportní řetězec MeSH
• inhibitory MAO MeSH
• loxapin MeSH
• lurasidon hydrochlorid MeSH
• peroxid vodíku MeSH
• piperaziny MeSH
• reaktivní formy kyslíku MeSH
• receptory neurotransmiterů MeSH
• thiofeny MeSH

The potential of nanomaterials use is huge, especially in fields such as medicine or industry. Due to widespread use of nanomaterials, their cytotoxicity and involvement in cellular pathways ought to be evaluated in detail. Nanomaterials can induce the production of a number of substances in cells, including reactive oxygen species (ROS), participating in physiological and pathological cellular processes. These highly reactive substances include: superoxide, singlet oxygen, hydroxyl radical, and hydrogen peroxide. For overall assessment, there are a number of fluorescent probes in particular that are very specific and selective for given ROS. In addition, due to the involvement of ROS in a number of cellular signaling pathways, understanding the principle of ROS production induced by nanomaterials is very important. For defense, the cells have a number of reparative and especially antioxidant mechanisms. One of the most potent antioxidants is a tripeptide glutathione. Thus, the glutathione depletion can be a characteristic manifestation of harmful effects caused by the prooxidative-acting of nanomaterials in cells. For these reasons, here we would like to provide a review on the current knowledge of ROS-mediated cellular nanotoxicity manifesting as glutathione depletion, including an overview of approaches for the detection of ROS levels in cells.

• Klíčová slova
• cell injury, fluorescence probes, glutathione, nanotoxicity, oxidative stress, reactive oxygen species,
• MeSH
• buňky účinky léků   metabolismus   MeSH
• glutathion metabolismus   MeSH
• lidé MeSH
• nanostruktury toxicita   MeSH
• oxidační stres účinky léků   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• glutathion MeSH
• reaktivní formy kyslíku MeSH

Ischemia reperfusion injury is a complex process consisting of a seemingly chaotic but actually organized and compartmentalized shutdown of cell function, of which oxidative stress is a key component. Studying oxidative stress, which results in an imbalance between reactive oxygen species (ROS) production and antioxidant defense activity, is a multi-faceted issue, particularly considering the double function of ROS, assuming roles as physiological intracellular signals and as mediators of cellular component damage. Herein, we propose a comprehensive overview of the tools available to explore oxidative stress, particularly in the study of ischemia reperfusion. Applying chemistry as well as biology, we present the different models currently developed to study oxidative stress, spanning the vitro and the silico, discussing the advantages and the drawbacks of each set-up, including the issues relating to the use of in vitro hypoxia as a surrogate for ischemia. Having identified the limitations of historical models, we shall study new paradigms, including the use of stem cell-derived organoids, as a bridge between the in vitro and the in vivo comprising 3D intercellular interactions in vivo and versatile pathway investigations in vitro. We shall conclude this review by distancing ourselves from "wet" biology and reviewing the in silico, computer-based, mathematical modeling, and numerical simulation options: (a) molecular modeling with quantum chemistry and molecular dynamic algorithms, which facilitates the study of molecule-to-molecule interactions, and the integration of a compound in a dynamic environment (the plasma membrane...); (b) integrative systemic models, which can include many facets of complex mechanisms such as oxidative stress or ischemia reperfusion and help to formulate integrated predictions and to enhance understanding of dynamic interaction between pathways.

• Klíčová slova
• ROS, animal models, antioxidant factors, ischemia-reperfusion injury, molecular modeling models, organoids, oxidative stress,
• MeSH
• buněčné linie MeSH
• lidé MeSH
• modely nemocí na zvířatech * MeSH
• molekulární modely MeSH
• oxidační stres * MeSH
• reaktivní formy kyslíku MeSH
• reperfuzní poškození metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• reaktivní formy kyslíku MeSH

Increasing evidence points to the respiratory Complex II (CII) as a source and modulator of reactive oxygen species (ROS). Both functional loss of CII as well as its pharmacological inhibition can lead to ROS generation in cells, with a relevant impact on the development of pathophysiological conditions, i.e. cancer and neurodegenerative diseases. While the basic framework of CII involvement in ROS production has been defined, the fine details still await clarification. It is important to resolve these aspects to fully understand the role of CII in pathology and to explore its therapeutic potential in cancer and other diseases.

• Klíčová slova
• OXPHOS, Respiratory complex II, cancer, mitochondria, reactive oxygen species, succinate, succinate dehydrogenase, tricarboxylic acid cycle,
• MeSH
• cílená molekulární terapie * MeSH
• lidé MeSH
• mitochondriální nemoci farmakoterapie   metabolismus   patologie   MeSH
• mitochondrie metabolismus   patologie   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• respirační komplex II metabolismus   MeSH
• transport elektronů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• reaktivní formy kyslíku MeSH
• respirační komplex II MeSH

Impairment of mitochondrial metabolism, particularly the electron transport chain (ETC), as well as increased oxidative stress might play a significant role in pathogenesis of Alzheimer's disease (AD). Some effects of drugs used for symptomatic AD treatment may be related to their direct action on mitochondrial function. In vitro effects of pharmacologically different cognitives (galantamine, donepezil, rivastigmine, 7-MEOTA, memantine) and nootropic drugs (latrepirdine, piracetam) were investigated on selected mitochondrial parameters: activities of ETC complexes I, II + III, and IV, citrate synthase, monoamine oxidase (MAO), oxygen consumption rate, and hydrogen peroxide production of pig brain mitochondria. Complex I activity was decreased by galantamine, donepezil, and memantine; complex II + III activity was increased by galantamine. None of the tested drugs caused significant changes in the rate of mitochondrial oxygen consumption, even at high concentrations. Except galantamine, all tested drugs were selective MAO-A inhibitors. Latrepirdine, donepezil, and 7-MEOTA were found to be the most potent MAO-A inhibitors. Succinate-induced mitochondrial hydrogen peroxide production was not significantly affected by the drugs tested. The direct effect of cognitives and nootropics used in the treatment of AD on mitochondrial respiration is relatively small. The safest drugs in terms of disturbing mitochondrial function appear to be piracetam and rivastigmine. The MAO-A inhibition by cognitives and nootropics may also participate in mitochondrial neuroprotection. The results support the future research aimed at measuring the effects of currently used drugs or newly synthesized drugs on mitochondrial functioning in order to understand their mechanism of action.

• Klíčová slova
• Cognitives, Mitochondrial respiration, Monoamine oxidase, Nootropics, Reactive oxygen species,
• MeSH
• Alzheimerova nemoc metabolismus   MeSH
• cholinesterasové inhibitory farmakologie   MeSH
• donepezil MeSH
• galantamin metabolismus   MeSH
• indany farmakologie   MeSH
• kognice účinky léků   MeSH
• memantin farmakologie   MeSH
• mitochondrie účinky léků   metabolismus   MeSH
• monoaminoxidasa účinky léků   metabolismus   MeSH
• mozek účinky léků   metabolismus   MeSH
• nootropní látky farmakologie   MeSH
• piperidiny farmakologie   MeSH
• prasata MeSH
• rivastigmin farmakologie   MeSH
• spotřeba kyslíku účinky léků   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cholinesterasové inhibitory MeSH
• donepezil MeSH
• galantamin MeSH
• indany MeSH
• memantin MeSH
• monoaminoxidasa MeSH
• nootropní látky MeSH
• piperidiny MeSH
• rivastigmin MeSH

In recent years, excessive oxidative metabolism has been reported as a critical determinant of pathogenicity in many diseases. The advent of a simple tool that can provide a physiological readout of oxidative stress would be a major step towards monitoring this dynamic process in biological systems, while also improving our understanding of this process. Ultra-weak photon emission (UPE) has been proposed as a potential tool for measuring oxidative processes due to the association between UPE and reactive oxygen species. Here, we used HL-60 cells as an in vitro model to test the potential of using UPE as readout for dynamically monitoring oxidative stress after inducing respiratory burst. In addition, to probe for possible changes in oxidative metabolism, we performed targeted metabolomics on cell extracts and culture medium. Lastly, we tested the effects of treating cells with the NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI). Our results show that UPE can be used as readout for measuring oxidative stress metabolism and related processes.

• MeSH
• buněčné extrakty chemie   MeSH
• fotometrie metody   MeSH
• HL-60 buňky MeSH
• kultivační média chemie   MeSH
• lidé MeSH
• metabolomika MeSH
• oxidační stres * MeSH
• reaktivní formy kyslíku analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• buněčné extrakty MeSH
• kultivační média MeSH
• reaktivní formy kyslíku MeSH