BACKGROUND: Elevated brain levels of kynurenic acid (KYNA), a metabolite in the kynurenine pathway, are associated with cognitive dysfunctions, which are nowadays often considered as fundamental characteristics of several psychopathologies; however, the role of KYNA in mental illnesses, such as schizophrenia, is not fully elucidated. This study aimed to assess KYNA levels in the prefrontal cortex (PFC) of rats prenatally treated with methylazoxymethanol (MAM) acetate, i.e., a well-validated neurodevelopmental animal model of schizophrenia. The effects of an early pharmacological modulation of the endogenous cannabinoid system were also evaluated. METHODS: Pregnant Sprague-Dawley rats were treated with MAM (22 mg/kg, ip) or its vehicle at gestational day 17. Male offspring were treated with the cannabinoid CB1 receptor antagonist/inverse agonist AM251 (0.5 mg/kg/day, ip) or with the typical antipsychotic haloperidol (0.6 mg/kg/day, ip) from postnatal day (PND) 19 to PND39. The locomotor activity and cognitive performance were assessed in the novel object recognition test and the open field test in adulthood. KYNA levels in the PFC of prenatally MAM-treated rats were also assessed. RESULTS: A significant cognitive impairment was observed in prenatally MAM-treated rats (p < 0.01), which was associated with enhanced PFC KYNA levels (p < 0.05). The peripubertal AM251, but not haloperidol, treatment ameliorated the cognitive deficit (p < 0.05), by normalizing the PFC KYNA content in MAM rats. CONCLUSIONS: The present findings suggest that the cognitive deficit observed in MAM rats may be related to enhanced PFC KYNA levels which could be, in turn, mediated by the activation of cannabinoid CB1 receptor. These results further support the modulation of brain KYNA levels as a potential therapeutic strategy to ameliorate the cognitive dysfunctions in schizophrenia.
- MeSH
- antipsychotika farmakologie MeSH
- haloperidol farmakologie MeSH
- kognitivní dysfunkce metabolismus farmakoterapie MeSH
- krysa rodu rattus MeSH
- kyselina kynurenová * metabolismus MeSH
- methylazoxymethanolacetát * analogy a deriváty MeSH
- modely nemocí na zvířatech MeSH
- piperidiny farmakologie MeSH
- potkani Sprague-Dawley * MeSH
- prefrontální mozková kůra * metabolismus účinky léků MeSH
- pyrazoly farmakologie MeSH
- receptor kanabinoidní CB1 metabolismus MeSH
- schizofrenie * metabolismus farmakoterapie MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice * metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Cobalt is an essential trace element, but it can also rarely cause cobalt toxicity due to its release from cobalt-containing medical devices. Currently, there are no approved selective cobalt chelators, which would represent an optimal treatment modality. OBJECTIVE: This study aimed to develop a simple and complex methodological approach for screening potential cobalt chelators and evaluating their potential toxicity. METHODS: Firstly, a simple spectrophotometric assay employing 1-nitroso-2-naphthol-3,6- disulfonic acid disodium salt (NNDSA) for screening cobalt chelation was standardized at a pathophysiologically relevant range of pH 4.5-7.5. Then, the suitability of the method was verified using four known metal chelators (EDTA, 8-hydroxyquinoline, chloroxine and nitroxoline). As cobalt can catalyse the Fenton reaction, the potential toxicity of cobalt-chelator complexes was also determined by employing a novel HPLC method with coulometric detection. The effect on erythrocyte haemolysis was tested as well. RESULTS: The NNDSA method had high sensitivity enabling the detection of 25-200 nM of cobalt ions depending on pH conditions. Measurements could be carried out in a wide range of wavelengths from 470 to 540 nm. All tested complexes of the selected chelators decreased the rate of the Fenton reaction. Interestingly, chloroxine mixed with cobalt ions caused marked lysis of erythrocytes in contrast to the other compounds. CONCLUSION: The described complex methodological approach could serve as a simple yet precise tool for evaluating novel, effective and safe cobalt chelators.
- MeSH
- chelátory * MeSH
- ionty MeSH
- kobalt * chemie MeSH
- oxychinolin MeSH
- Publikační typ
- časopisecké články MeSH
Background: Antimicrobial submicrometer particles are being studied as promising interventions against a wide range of skin conditions, such as fungal or bacterial infections. Aims: To submicronize chloroxine, the crystalline compound 5,7-dichloro-8-hydroxyquinoline, by nanoprecipitation and characterize the resulting assemblies. Methods: The chloroxine particles were stabilized by a nonionic surfactant and were studied by a broth microdilution assay against 20 medically important bacteria and fungi. The intervention was studied using a murine model of skin irritation. Results & conclusion: Chloroxine nanoparticles with a diameter of 600-800 nm exhibit good tolerability in terms of skin irritation in vivo and good antimicrobial activity. Thus, the fabricated formulation shows great promise for interventions for both cutaneous infection control and prophylaxis.
In this work, we report two concepts of drug delivery based on small-molecule drug conjugates with the ability of specific targeting and drug release monitoring via ratiometric fluorescence. The functionality of these concepts has been verified by two model systems consisting of three parts: (i) fluorescent aminoBODIPY for real-time detection of conjugate cleavage, (ii) a c(RGDfK) peptide specific for αvβ3 integrin receptors targeting angiogenesis in most solid tumors or redBODIPY for conjugate cleavage monitoring via FRET, and (iii) pegylated-2-phenyl-3-hydroxy-4(1H)-quinolinone (3HQ) as a model drug. The model drug release is based on a self-immolative disulfide linker sensitive to environments containing thiols, especially glutathione, which is overexpressed in cancer cells. The results show effective thiol-mediated cleavage of the fluorescent reporter and the subsequent liberation of the drug in a tube. The conjugate with c(RGDfK) was confirmed to penetrate the cells via interaction with integrin receptors. Drug release from this conjugate is possible to monitor inside the cells. Further, the synthetic approach to the conjugates and the method of fluorescence monitoring of the drug release have also been described.
- MeSH
- fluorescence MeSH
- fluorescenční barviva chemie MeSH
- glutathion metabolismus MeSH
- HeLa buňky MeSH
- hydroxychinoliny aplikace a dávkování farmakokinetika MeSH
- integrin alfaVbeta3 metabolismus MeSH
- lidé MeSH
- nosiče léků chemie farmakologie MeSH
- oligopeptidy chemie farmakologie MeSH
- sloučeniny boru chemie MeSH
- uvolňování léčiv MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
AIMS: The objective of the study was to evaluate the antimicrobial interactions between two volatile agents, Cinnamomum cassia essential oil (CCEO) and 8-hydroxyquinoline (8-HQ) against Staphylococcus aureus strains in liquid and vapour phases. METHODS AND RESULTS: In vitro antimicrobial effect of CCEO in combination with 8-HQ was evaluated against 12 strains of S. aureus by broth volatilization chequerboard method. Results show additive effects against all S. aureus strains for both phases. In several cases, sums of fractional inhibitory concentration values of our test combinations were lower than 0·6, which can be considered as a strong additive interaction. Moreover, composition of CCEO was analysed by gas chromatography-mass spectrometry analysis. In the CCEO, 26 compounds in total were identified, where (E)-cinnamaldehyde was the predominant compound, followed by cinnamyl acetate, α-copaene, bornyl acetate and caryophyllene. CONCLUSIONS: Results showed additive in vitro growth-inhibitory effect of CCEO and 8-HQ combination against various standard strains and clinical isolates of S. aureus. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on antibacterial effect of 8-HQ and CCEO combination in liquid and vapour phases. Results of the study suggest these agents as potential candidates for development of new anti-staphylococcal applications that can be used in the inhalation therapy against respiratory infections.
- MeSH
- akrolein analogy a deriváty chemie MeSH
- antibakteriální látky farmakologie MeSH
- mikrobiální testy citlivosti MeSH
- oleje prchavé farmakologie MeSH
- oxychinolin farmakologie MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- skořicovník čínský chemie MeSH
- Staphylococcus aureus účinky léků MeSH
- Publikační typ
- časopisecké články MeSH
An increased number of sulfate-reducing bacteria is often isolated from faeces of patients with gastrointestinal diseases, which can be the cause of the development of bowel inflammation. Frequent use of antibiotics causes the resistance of intestinal microorganisms and ineffective treatment of these diseases. The antimicrobial activity and biological properties of the selected ring-substituted 8-hydroxyquinoline-2-carboxanilides against Desulfovibrio piger Vib-7 were studied. The addition of these compounds in the cultivation medium inhibited the bacterial growth and the process of sulfate reduction dose-dependently. A significant cytotoxic activity under the influence of ring-substituted 8-hydroxyquinoline-2-carboxanilides was determined. The strongest cytotoxic effect of the derivatives was observed for compounds 8-hydroxy-N-(3-methoxyphenyl)quinoline-2-carboxamide and 8-hydroxy-N-(3-trifluoromethylphenyl)quinoline-2-carboxamide that caused a low survival of D. piger Vib-7 in concentration 17 μM and high toxicity rates.
- Klíčová slova
- 8-hydroxychinolin-2-karboxanilidy, redukce síranu, Desulfovibrio piger,
- MeSH
- antibakteriální látky farmakologie chemie klasifikace MeSH
- Bacteria klasifikace metabolismus MeSH
- bakteriologické techniky metody MeSH
- Desulfovibrio * klasifikace patogenita účinky léků MeSH
- hydroxychinoliny * farmakologie klasifikace MeSH
- idiopatické střevní záněty mikrobiologie MeSH
- mikrobiální viabilita účinky léků MeSH
- ulcerózní kolitida * farmakoterapie mikrobiologie patologie MeSH
- vyvíjení léků MeSH
- Publikační typ
- práce podpořená grantem MeSH
Wilson's disease is a genetic disorder that causes excessive accumulation of copper in the body, leading to toxic damage, especially in the liver and nervous system. The current treatment cause burdensome side effects. We describe the use of chemically modified biopolymer carriers based on microcrystalline cellulose and chitosan containing the highly specific copper chelator 8-hydroxyquinoline as a new type of therapy for Wilson's disease. The chelators can scavenges copper ions released from food during digestion and copper ions present in secretions in the gastrointestinal tract. Because the chelator is covalently bound to indigestible biopolymer carriers (crosslinked chitosan or modified cellulose), it is not taken up by the gastrointestinal tract and it can be eliminated through the feces, avoiding unwanted side effects. This concept was tested on Wistar rats, which received a radioactive 64CuCl2 solution together with the polymers with covalently bound 8-hydroxyquinoline through a gastric probe. 64Copper complex uptake from the gastrointestinal tract was significantly inhibited by both chelating polymers. With the modified polymers, the presence of 64Cu was detected mostly in the gastrointestinal tract, not in the internal organs. These findings indicate modified cellulose and crosslinked chitosan, with covalently bound 8-hydroxyquinoline exhibited the potential to be excellent therapeutics for treating Wilson's disease.
- MeSH
- celulosa aplikace a dávkování farmakokinetika MeSH
- chitosan aplikace a dávkování farmakokinetika MeSH
- gastrointestinální trakt metabolismus MeSH
- hepatolentikulární degenerace farmakoterapie metabolismus MeSH
- měď MeSH
- oxychinolin aplikace a dávkování farmakokinetika MeSH
- potkani Wistar MeSH
- radioizotopy mědi aplikace a dávkování farmakokinetika MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- klinické zkoušky jako téma MeSH
- kynurenin-3-monooxygenasa nedostatek MeSH
- kyselina kynurenová MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- schizofrenie * patofyziologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- zprávy MeSH
With aim to develop effective proof-of-concept approach which can be used in a development of new preparations for the inhalation therapy, we designed a new screening method for simple and rapid simultaneous determination of antibacterial potential of plant volatiles in the liquid and the vapour phase at different concentrations. In addition, EVA (ethylene vinyl acetate) capmat™ as vapour barrier cover was used as reliable modification of thiazolyl blue tetrazolium bromide (MTT) assay for cytotoxicity testing of volatiles on microtiter plates. Antibacterial activity of carvacrol, cinnamaldehyde, eugenol, 8-hydroxyquinoline, thymol and thymoquinone was determined against Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae using new broth microdilution volatilization method. The cytotoxicity of these compounds was evaluated using MTT test in lung fibroblast cells MRC-5. The most effective antibacterial agents were 8-hydroxyquinoline and thymoquinone with the lowest minimum inhibitory concentrations (MICs) ranging from 2 to 128μg/mL, but they also possessed the highest toxicity in lung cell lines with half maximal inhibitory concentration (IC50) values 0.86-2.95μg/mL. The lowest cytotoxicity effect was identified for eugenol with IC50 295.71μg/mL, however this compound produced only weak antibacterial potency with MICs 512-1024μg/mL. The results demonstrate validity of our novel broth microdilution volatilization method, which allows cost and labour effective high-throughput antimicrobial screening of volatile agents without need of special apparatus. In our opinion, this assay can also potentially be used for development of various medicinal, agricultural, and food applications that are based on volatile antimicrobials.
- MeSH
- akrolein analogy a deriváty chemie MeSH
- antibakteriální látky chemie MeSH
- benzochinony chemie MeSH
- buněčné linie MeSH
- eugenol chemie MeSH
- fytonutrienty chemie MeSH
- Haemophilus influenzae účinky léků MeSH
- lidé MeSH
- mikrobiální testy citlivosti metody MeSH
- monoterpeny chemie MeSH
- oxychinolin chemie MeSH
- Staphylococcus aureus účinky léků MeSH
- Streptococcus pneumoniae účinky léků MeSH
- těkavé organické sloučeniny chemie MeSH
- tetrazoliové soli MeSH
- thiazoly MeSH
- thymol chemie MeSH
- volatilizace * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
We report on a Lab-On-Valve (LOV) configuration for analyte preconcentration from milliliter sample volumes using confluent mixing in the holding coil for in-line addition of loading buffer. The system was applied to the spectrophotometric determination of iron(II) in acidified seawater using 1,10-phenanthroline as color reagent. A cellulose-based chelating sorbent containing 8-hydroxyquinoline was used for the first time in LOV and excellent retention behavior and loading capacity were found. The flow system employs a syringe pump for handling all solutions (sorbent suspension, loading buffer, water, eluent, and color reagent) and a peristaltic pump for sample propulsion and includes a fit-for-purpose 14 cm long detection glass flow cell and a bubble trap for in-line carrier degasification. Advantage was taken of the LOV flow-through port to keep the eluted analytes for re-aspiration for subsequent chromogenic reaction. In effect, a universal analyzer configuration and preconcentration procedure was developed, which is combinable with other analytes, sorbents, and reagents. Among the studied parameters were the compositions, pH, volumes, and flow rates of loading buffer, eluent, and color reagent, as well as the microcolumn size, repeatability, and system stability. Reproducibility of 4.1% RSD over the entire working range, a LOD of down to 5 nmol L(-1), sampling frequency of 12h(-1), and linearity up to 1 µmol L(-1) for 3.3 mL of sample were obtained and applicability to real samples was demonstrated. It was proven that both Fe(III) and Fe(II) were retained and yielded similar recovery and sensitivity values. The method was applied to coastal seawater samples and spiking experiments yielded recovery values close to 100%.
- MeSH
- barva MeSH
- celulosa chemie MeSH
- chelátory chemie MeSH
- extrakce na pevné fázi MeSH
- fenantroliny chemie MeSH
- koncentrace vodíkových iontů MeSH
- limita detekce * MeSH
- metody pro přípravu analytických vzorků přístrojové vybavení metody MeSH
- mořská voda chemie MeSH
- oxychinolin chemie MeSH
- pufry MeSH
- reprodukovatelnost výsledků MeSH
- železo analýza chemie izolace a purifikace MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
