Superparamagnetic iron oxide nanoparticles (SPIOn) are widely used as a contrast agent for cell labeling. Macrophages are the first line of defense of organisms in contact with nanoparticles after their administration. In this study we investigated the effect of silica-coated nanoparticles (γ-Fe2O3-SiO2) with or without modification by an ascorbic acid (γ-Fe2O3-SiO2-ASA), which is meant to act as an antioxidative agent on rat peritoneal macrophages. Both types of nanoparticles were phagocytosed by macrophages in large amounts as confirmed by transmission electron microscopy and Prusian blue staining, however they did not substantially affect the viability of exposed cells in monitored intervals. We further explored cytotoxic effects related to oxidative stress, which is frequently documented in cells exposed to nanoparticles. Our analysis of double strand breaks (DSBs) marker γH2AX showed an increased number of DSBs in cells treated with nanoparticles. Nanoparticle exposure further revealed only slight changes in the expression of genes involved in oxidative stress response. Lipid peroxidation, another marker of oxidative stress, was not significantly affirmed after nanoparticle exposure. Our data indicate that the effect of both types of nanoparticles on cell viability, or biomolecules such as DNA or lipids, was similar; however the presence of ascorbic acid, either bound to the nanoparticles or added to the cultivation medium, worsened the negative effect of nanoparticles in various tests performed. The attachment of ascorbic acid on the surface of nanoparticles did not have a protective effect against induced cytotoxicity, as expected.

• MeSH
• antioxidancia metabolismus   toxicita   MeSH
• krysa rodu rattus MeSH
• kultivované buňky MeSH
• kyselina askorbová metabolismus   toxicita   MeSH
• magnetické nanočástice toxicita   MeSH
• peritoneální makrofágy účinky léků   metabolismus   MeSH
• potkani Wistar MeSH
• synergismus léků MeSH
• viabilita buněk účinky léků   fyziologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

β-carotene is a natural compound with significant antioxidant activity. However, its poor solubility in water and low stability reduce its potential application. Innovative polyplexes based on the combination of amphiphilic chitosan assembled with DNA have been developed using a solvent-free, simple and low-cost method with the aim to load, retain and enhance the antioxidant capability of β-carotene. The polyplexes, with dimension about 100 nm, and excellent stability, were able to hold up to 400 μg of β-carotene per mg of the carrier, with minimal loss till two weeks. The antioxidant activity was significantly enhanced after loading, as demonstrated using two well known methods. Cytotoxicity assay confirmed the not toxicity of the system. The results suggest the polyplexes as an excellent candidate to develop formulation able to preserve and enhance the peculiarities of compounds which are used mainly in food, cosmetic and pharmaceutic but with still some limitations.

• MeSH
• antioxidancia chemie   farmakologie   toxicita   MeSH
• beta-karoten chemie   farmakologie   toxicita   MeSH
• bifenylové sloučeniny chemie   MeSH
• buňky NIH 3T3 MeSH
• chitosan chemie   MeSH
• DNA chemie   MeSH
• hydrofobní a hydrofilní interakce * MeSH
• myši MeSH
• pikráty chemie   MeSH
• rozpustnost MeSH
• stabilita léku MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Aroylhydrazone iron chelators such as salicylaldehyde isonicotinoyl hydrazone (SIH) protect various cells against oxidative injury and display antineoplastic activities. Previous studies have shown that a nitro-substituted hydrazone, namely, NHAPI, displayed markedly improved plasma stability, selective antitumor activity, and moderate antioxidant properties. In this study, we prepared four series of novel NHAPI derivatives and explored their iron chelation activities, anti- or pro-oxidant effects, protection against model oxidative injury in the H9c2 cell line derived from rat embryonic cardiac myoblasts, cytotoxicities to the corresponding noncancerous H9c2 cells, and antiproliferative activities against the MCF-7 human breast adenocarcinoma and HL-60 human promyelocytic leukemia cell lines. Nitro substitution had both negative and positive effects on the examined properties, and we identified new structure-activity relationships. Naphthyl and biphenyl derivatives showed selective antiproliferative action, particularly in the breast adenocarcinoma MCF-7 cell line, where they exceeded the selectivity of the parent compound NHAPI. Of particular interest is a compound prepared from 2-hydroxy-5-methyl-3-nitroacetophenone and biphenyl-4-carbohydrazide, which protected cardiomyoblasts against oxidative injury at 1.8 ± 1.2 μM with 24-fold higher selectivity than SIH. These compounds will serve as leads for further structural optimization and mechanistic studies.

• MeSH
• antioxidancia chemická syntéza   chemie   farmakologie   toxicita   MeSH
• chelátory železa chemická syntéza   chemie   farmakologie   toxicita   MeSH
• hydrazony chemická syntéza   chemie   farmakologie   toxicita   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• molekulární struktura MeSH
• nádorové buněčné linie MeSH
• oxidační stres účinky léků   MeSH
• protinádorové látky chemická syntéza   chemie   farmakologie   toxicita   MeSH
• radioizotopy železa MeSH
• stabilita léku MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: The aim of this work was to compare water and organic extracts, infusions and tinctures from flowers and leaves of Calendula officinalis in terms of their biological activity and composition. The purpose of work was investigation whether the leaves and stems are really the waste or they contain interesting substances which could be utilized. Antimicrobial, antifungal, antioxidant and anti-inflammatory activities were studied. Then, the ability to inhibit collagenase was studied as well. Cytotoxicity was tested for all the samples on mammalian cell lines. METHODS: To determine the composition of extracts, infusions and tinctures phytochemical analysis (the set of colour reactions for the detection of groups of biologically active compounds) was carried out and showed that samples from flowers and leaves contain the same groups of biologically active substances (proteins and amino acids, reducing sugars, flavonoids, saponins, phenolics, terpenoids, steroids, glycosides). The antimicrobial activity of tested samples was proved, where the most sensitive bacterium was Micrococcus luteus and the most sensitive yeast was Geotrichum candidum. RESULTS: The study of anti-collagenase activity has shown that the enzymatic reaction of collagenase was affected by all tested samples and their effect was concentration dependent. Cytotoxicity of water and methanol extracts at cell lines HEK 293T and HepG2 was observed. CONCLUSION: Cells HepG2 were more sensitive than cells HEK 293T. Using cell line RAW 264.7, antiinflammatory activity of all samples was observed. Tincture of leaves was the most effective.

• MeSH
• antiflogistika izolace a purifikace   toxicita   MeSH
• antiinfekční látky izolace a purifikace   toxicita   MeSH
• antioxidancia izolace a purifikace   toxicita   MeSH
• buněčné linie MeSH
• buňky Hep G2 MeSH
• HEK293 buňky MeSH
• květy chemie   MeSH
• lidé MeSH
• listy rostlin chemie   MeSH
• měsíček chemie   MeSH
• rostlinné extrakty izolace a purifikace   toxicita   MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

We discovered a small series of hit compounds that show multitargeting activities against key targets in Alzheimer's disease (AD). The compounds were designed by combining the structural features of the anti-AD drug donepezil with clioquinol, which is able to chelate redox-active metals, thus decreasing metal-driven oxidative phenomena and β-amyloid (Aβ)-mediated neurotoxicity. The majority of the new hybrid compounds selectively target human butyrylcholinesterase at micromolar concentrations and effectively inhibit Aβ self-aggregation. In addition, compounds 5-chloro-7-((4-(2-methoxybenzyl)piperazin-1-yl)methyl)-8-hydroxyquinoline (1 b), 7-((4-(2-methoxybenzyl)piperazin-1-yl)methyl)-8-hydroxyquinoline (2 b), and 7-(((1-benzylpiperidin-4-yl)amino)methyl)-5-chloro-8-hydroxyquinoline (3 a) are able to chelate copper(II) and zinc(II) and exert antioxidant activity in vitro. Importantly, in the case of 2 b, the multitarget profile is accompanied by high predicted blood-brain barrier permeability, low cytotoxicity in T67 cells, and acceptable toxicity in HUVEC primary cells.

• MeSH
• Alzheimerova nemoc farmakoterapie   MeSH
• amyloidní beta-protein antagonisté a inhibitory   metabolismus   MeSH
• antioxidancia chemie   terapeutické užití   toxicita   MeSH
• butyrylcholinesterasa chemie   metabolismus   MeSH
• chelátory chemie   MeSH
• cholinesterasové inhibitory chemie   terapeutické užití   toxicita   MeSH
• endoteliální buňky pupečníkové žíly (lidské) MeSH
• hematoencefalická bariéra metabolismus   MeSH
• indany chemie   terapeutické užití   toxicita   MeSH
• jodchlorhydroxychin chemie   terapeutické užití   toxicita   MeSH
• lidé MeSH
• měď chemie   MeSH
• nádorové buněčné linie MeSH
• oxychinolin chemie   terapeutické užití   toxicita   MeSH
• piperidiny chemie   terapeutické užití   toxicita   MeSH
• racionální návrh léčiv MeSH
• viabilita buněk účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zinek chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Coupling of two distinct pharmacophores, tacrine and trolox, endowed with different biological properties, afforded 21 hybrid compounds as novel multifunctional candidates against Alzheimer's disease. Several of them showed improved inhibitory properties toward acetylcholinesterase (AChE) in relation to tacrine. These hybrids also scavenged free radicals. Molecular modeling studies in tandem with kinetic analysis exhibited that these hybrids target both catalytic active site as well as peripheral anionic site of AChE. In addition, incorporation of the moiety bearing antioxidant abilities displayed negligible toxicity on human hepatic cells. This striking effect was explained by formation of nontoxic metabolites after 1 h incubation in human liver microsomes system. Finally, tacrine-trolox hybrids exhibited low in vivo toxicity after im administration in rats and potential to penetrate across blood-brain barrier. All of these outstanding in vitro results in combination with promising in vivo outcomes highlighted derivative 7u as the lead structure worthy of further investigation.

• MeSH
• acetylcholinesterasa chemie   MeSH
• antioxidancia chemická syntéza   farmakologie   toxicita   MeSH
• cholinesterasové inhibitory chemická syntéza   farmakologie   toxicita   MeSH
• chromany (dihydrobenzopyrany) chemie   farmakologie   toxicita   MeSH
• hematoencefalická bariéra MeSH
• hepatocyty účinky léků   MeSH
• injekce intramuskulární MeSH
• jaterní mikrozomy účinky léků   metabolismus   MeSH
• katalýza MeSH
• kinetika MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• ligandy MeSH
• molekulární modely MeSH
• potkani Wistar MeSH
• racionální návrh léčiv MeSH
• scavengery volných radikálů chemická syntéza   farmakologie   MeSH
• takrin chemie   farmakologie   toxicita   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Coumarins are a large group of substances, primarily of plant origin. Like their more intensively examined congeners flavonoids, many of them are antioxidants. Although such properties may be advantageous in cardiovascular diseases, it has been shown that coumarins exhibit direct effects on the cardiovascular system which are not based on antioxidant activity. The most common example is the well-known drug warfarin, a synthetic compound derived from natural dicoumarol. Moreover, other coumarins have been shown to possess antiplatelet and vasodilatory potential. Interestingly, the former effect may be mediated by the inhibition of various pathways leading to platelet aggregation, their differing effects on those pathways being due to structural differences between the various coumarins. Conversely, their vasodilatory potential is linked in the majority of cases to the inhibition of increases in intracellular calcium concentration in vascular smooth muscle cells, and in several coumarins also to NO-mediated vasodilatation. Available data on both activities are summarized in this review. At the end of this review, relevant data are provided from a few studies testing the in vivo effects of coumarins on major cardiovascular diseases; the clinical use of warfarin and other coumarin anticoagulants, as well as the limited data on the clinical use of coumarins in chronic venous insufficiency and the possible toxicological effects of coumarins.

• MeSH
• antioxidancia farmakokinetika   farmakologie   terapeutické užití   toxicita   MeSH
• inhibitory agregace trombocytů farmakokinetika   farmakologie   terapeutické užití   toxicita   MeSH
• kardiovaskulární nemoci krev   farmakoterapie   metabolismus   patofyziologie   MeSH
• klinické zkoušky jako téma MeSH
• kumariny farmakokinetika   farmakologie   terapeutické užití   toxicita   MeSH
• lidé MeSH
• molekulární struktura MeSH
• objevování léků MeSH
• vazodilatancia farmakokinetika   farmakologie   terapeutické užití   toxicita   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Epigallocatechin gallate (EGCG) is an antioxidant found in green tea. In this study, male Wistar rats were subjected either to partial hepatectomy (PHx), or a sham operation (LAP). Twenty-four hours after surgery, hepatocytes were isolated and treated with various concentrations of EGCG for up to 72 h. We then measured markers of cell viability, oxidative stress, DNA synthesis, and caspase activity. Morphological criteria, cell viability tests, and albumin synthesis revealed toxicity starting at 10 μmol/L. DNA synthesis was higher in hepatocytes isolated from rats after PHx and inhibited by EGCG. Furthermore, EGCG increased the activity of caspases 3 and 7, seen more in hepatocytes from PHx rats. In conclusion, EGCG at a concentration of 10 μmol/L was toxic for hepatocytes isolated from both PHx and LAP rats.

• MeSH
• antioxidancia aplikace a dávkování   toxicita   MeSH
• DNA biosyntéza   MeSH
• hepatektomie * MeSH
• hepatocyty účinky léků   enzymologie   metabolismus   MeSH
• kaspasa 3 metabolismus   MeSH
• kaspasa 7 metabolismus   MeSH
• katechin aplikace a dávkování   analogy a deriváty   toxicita   MeSH
• krysa rodu rattus MeSH
• oxidační stres účinky léků   MeSH
• potkani Wistar MeSH
• primární buněčná kultura MeSH
• viabilita buněk účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVES: Melatonin is a hormone with strong antioxidant activity. It is biosynthesized in the pineal gland and serves in the biological signaling and control of the circadian rhythm. Though there is evidence of beneficial effects of melatonin, the substance was not investigated in greater details associated with specific regulation of oxidative stress in organs and tissues. DESIGN: The experiment is based on exposure of BALB/c mice to doses from 10 µg to 1mg of melatonin. Mice were euthanized after one and 24 hours, respectively. Biochemical markers in plasma, ferric reducing antioxidant power (FRAP), thiobarbituric acid reactive substances (TBARS) and activity of caspase-3 were examined in selected organs. RESULTS: We confirmed significant alteration in high-density lipoprotein and total cholesterols and glucose. After one day, levels of glucose and high-density lipoprotein cholesterol were decreased, while total cholesterol increased in a dose dependent manner. FRAP values increased in spleen, liver, kidney, heart, and brain indicating a growing potential of low molecular weight antioxidants 24 hours after exposure. However, TBARS values indicating oxidative stress were elevated in heart, kidney, and liver. CONCLUSIONS: Despite the antioxidant properties of melatonin, its effect on the organism is more complicated. It influences not only the oxidative homeostasis but also the basal metabolism, as represented by, e.g., cholesterol and glucose. This substance could thus be used for therapeutical purposes such as amelioration of pathologies associated with generation of reactive species or some metabolic dysfunctions.

• MeSH
• antioxidancia metabolismus   toxicita   MeSH
• bazální metabolismus účinky léků   fyziologie   MeSH
• biologické markery metabolismus   MeSH
• homeostáza účinky léků   fyziologie   MeSH
• kaspasy metabolismus   MeSH
• látky reagující s kyselinou thiobarbiturovou metabolismus   MeSH
• melatonin metabolismus   toxicita   MeSH
• modely u zvířat MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• oxidační stres účinky léků   fyziologie   MeSH
• testy toxicity MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Despite a reasonable scientific interest in sexual selection, the general principles of health signalisation via ornamental traits remain still unresolved in many aspects. This is also true for the mechanism preserving honesty of carotenoid-based signals. Although it is widely accepted that this type of ornamentation reflects an allocation trade-off between the physiological utilisation of carotenoids (mainly in antioxidative processes) and their deposition in ornaments, some recent evidence suggests more complex interactions. Here, we further develop the models currently proposed to explain the honesty of carotenoid-based signalisation of heath status by adding the handicap principle concept regulated by testosterone. We propose that under certain circumstances carotenoids may be dangerous for the organism because they easily transform into toxic cleavage products. When reserves of other protective antioxidants are insufficient, physiological trade-offs may exist between maintenance of carotenoids for ornament expression and their removal from the body. Furthermore, we suggest that testosterone which enhances ornamentation by increasing carotenoid bioavailability may also promote oxidative stress and hence lower antioxidant reserves. The presence of high levels of carotenoids required for high-quality ornament expression may therefore represent a handicap and only individuals in prime health could afford to produce elaborate colourful ornaments. Although further testing is needed, this 'carotenoid maintenance handicap' hypothesis may offer a new insight into the physiological aspects of the relationship between carotenoid function, immunity and ornamentation.

• MeSH
• antioxidancia fyziologie   toxicita   MeSH
• imunitní systém fyziologie   MeSH
• karotenoidy fyziologie   toxicita   MeSH
• lidé MeSH
• oxidační stres fyziologie   MeSH
• pigmentace fyziologie   MeSH
• pohlavní dimorfismus MeSH
• sexuální chování zvířat fyziologie   MeSH
• signální transdukce MeSH
• teoretické modely MeSH
• testosteron fyziologie   MeSH
• vitamin E terapeutické užití   MeSH
• zdravotní stav MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH