Nejvíce citovaný článek - PubMed ID 4388022
Increased awareness of the impact of human activities on the environment has emerged in recent decades. One significant global environmental and human health issue is the development of materials that could potentially have negative effects. These materials can accumulate in the environment, infiltrate organisms, and move up the food chain, causing toxic effects at various levels. Therefore, it is crucial to assess materials comprising nano-scale particles due to the rapid expansion of nanotechnology. The aquatic environment, particularly vulnerable to waste pollution, demands attention. This review provides an overview of the behavior and fate of metallic nanoparticles (NPs) in the aquatic environment. It focuses on recent studies investigating the toxicity of different metallic NPs on aquatic organisms, with a specific emphasis on thiol-biomarkers of oxidative stress such as glutathione, thiol- and related-enzymes, and metallothionein. Additionally, the selection of suitable measurement methods for monitoring thiol-biomarkers in NPs' ecotoxicity assessments is discussed. The review also describes the analytical techniques employed for determining levels of oxidative stress biomarkers.
- Klíčová slova
- Aquatic organism, Glutathione, Mass spectrometry, Metallothionein, Oxidative stress,
- MeSH
- antioxidancia * metabolismus MeSH
- biologické markery * metabolismus MeSH
- chemické látky znečišťující vodu * toxicita analýza MeSH
- glutathion metabolismus MeSH
- kovové nanočástice * toxicita chemie MeSH
- lidé MeSH
- metalothionein metabolismus MeSH
- monitorování životního prostředí metody MeSH
- oxidační stres * účinky léků MeSH
- peptidy toxicita MeSH
- vodní organismy účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antioxidancia * MeSH
- biologické markery * MeSH
- chemické látky znečišťující vodu * MeSH
- glutathion MeSH
- metalothionein MeSH
- peptidy MeSH
Accidents with venomous bees are a serious worldwide health concern. Since the kidney has been reported as the main venom-target organ, the present study was undertaken to investigate the in vivo nephrotoxic effect of Algerian bee venom (ABV) (Apis mellifera intermissa) collected in the middle east of Algeria. A preliminary study was performed on ABV to identify the ABV using SDS-PAGE analysis and to determine the in vivo intraperitoneal median lethal dose (LD50) using the Probit analysis test. In vivo nephrotoxic effect was assessed through the determination of physiological and kidney biochemical markers in mice intraperitoneally injected with ABV at doses of 0.76 (D1); 1.14 (D2) and 2.29 mg/kg body weight (bwt) (D3), corresponding respectively to LD50/15, LD50/10, and LD50/5 (i.p. LD50=11.48 mg/kg bwt) for seven consecutive days. Results revealed a marked decrease in body weight gain and food intake, and an increase in absolute and relative kidney weights in ABV D2 and D3 treated mice compared with controls. Furthermore, ABV D2 and D3 resulted in a significant increase in serum creatinine, urea, and uric acid. ABV-induced oxidative stress was evidenced by a significant increase in kidney MDA level, and a significant depletion in kidney GSH level, and catalase activity. Meanwhile, no marked changes in the above-mentioned parameters were noticed in ABV D1. Accordingly, the adverse nephrotoxic effect of ABV was proved by the dose-dependent kidney histological changes. In summary, the results of the present study evidence that ABV at doses of 1.14 (D2) and 2.28 mg/kg body weight (bwt) can cause marked changes in kidney biochemical and major antioxidant markers, and histological architecture.
- MeSH
- antioxidancia farmakologie MeSH
- ledviny MeSH
- myši MeSH
- oxidační stres MeSH
- tělesná hmotnost MeSH
- včelí jedy * toxicita metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antioxidancia MeSH
- včelí jedy * MeSH
Titanium dioxide nanoparticles (TiO2 NPs) are used in a wide range of applications. Although inhalation of NPs is one of the most important toxicologically relevant routes, experimental studies on potential harmful effects of TiO2 NPs using a whole-body inhalation chamber model are rare. In this study, the profile of lymphocyte markers, functional immunoassays, and antioxidant defense markers were analyzed to evaluate the potential adverse effects of seven-week inhalation exposure to two different concentrations of TiO2 NPs (0.00167 and 0.1308 mg TiO2/m3) in mice. A dose-dependent effect of TiO2 NPs on innate immunity was evident in the form of stimulated phagocytic activity of monocytes in low-dose mice and suppressed secretory function of monocytes (IL-18) in high-dose animals. The effect of TiO2 NPs on adaptive immunity, manifested in the spleen by a decrease in the percentage of T-cells, a reduction in T-helper cells, and a dose-dependent decrease in lymphocyte cytokine production, may indicate immunosuppression in exposed mice. The dose-dependent increase in GSH concentration and GSH/GSSG ratio in whole blood demonstrated stimulated antioxidant defense against oxidative stress induced by TiO2 NP exposure.
Copper oxide nanoparticles (CuO NPs) are increasingly used in various industry sectors. Moreover, medical application of CuO NPs as antimicrobials also contributes to human exposure. Their toxicity, including toxicity to the immune system and blood, raises concerns, while information on their immunotoxicity is still very limited. The aim of our work was to evaluate the effects of CuO NPs (number concentration 1.40×106 particles/cm3, geometric mean diameter 20.4 nm) on immune/inflammatory response and antioxidant defense in mice exposed to 32.5 µg CuO/m3 continuously for 6 weeks. After six weeks of CuO NP inhalation, the content of copper in lungs and liver was significantly increased, while in kidneys, spleen, brain, and blood it was similar in exposed and control mice. Inhalation of CuO NPs caused a significant increase in proliferative response of T-lymphocytes after mitogenic stimulation and basal proliferative activity of splenocytes. CuO NPs significantly induced the production of IL-12p70, Th1-cytokine IFN-γ and Th2-cytokines IL-4, IL-5. Levels of TNF-α and IL-6 remained unchanged. Immune assays showed significantly suppressed phagocytic activity of granulocytes and slightly decreased respiratory burst. No significant differences in phagocytosis of monocytes were recorded. The percentage of CD3+, CD3+CD4+, CD3+CD8+, and CD3-CD19+ cell subsets in spleen, thymus, and lymph nodes did not differ between exposed and control animals. No changes in hematological parameters were found between the CuO NP exposed and control groups. The overall antioxidant protection status of the organism was expressed by evaluation of GSH and GSSG concentrations in blood samples. The experimental group exposed to CuO NPs showed a significant decrease in GSH concentration in comparison to the control group. In summary, our results indicate that sub-chronic inhalation of CuO NPs can cause undesired modulation of the immune response. Stimulation of adaptive immunity was indicated by activation of proliferation and secretion functions of lymphocytes. CuO NPs elicited pro-activation state of Th1 and Th2 lymphocytes in exposed mice. Innate immunity was affected by impaired phagocytic activity of granulocytes. Reduced glutathione was significantly decreased in mice exposed to CuO NPs.
- Klíčová slova
- antioxidant defense, copper oxide nanoparticles, cytokines, immune response, immunotoxicity, inflammation, lymphocytes, phagocytic activity and respiratory burst,
- MeSH
- adaptivní imunita MeSH
- antioxidancia MeSH
- cytokiny MeSH
- měď * toxicita MeSH
- myši MeSH
- nanočástice * toxicita MeSH
- oxidy MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antioxidancia MeSH
- cytokiny MeSH
- měď * MeSH
- oxidy MeSH
The objective of this study was to evaluate the concentrations of the total (T-GSH), oxidised (GSSG) and reduced (GSH) glutathione in the blood of dairy cows, assess the relationships of the phase and number of lactation, milk production, body condition score (BCS) and selected biochemical parameters on its concentrations. We analysed 79 samples of whole blood from dairy Holstein cows. The concentration of glutathione was assessed by the spectrophotometric enzymatic method. The whole dataset shows the mean concentration of T-GSH, GSSG and GSH of 803 ± 22 µmol/l, 23 ± 2.5 µmol/l and 757 ± 27 µmol/l, respectively. The GSH/GSSG ratio was 95 ± 17. The phase of the lactation had a significant impact on the levels of T-GSH and GSH, but the number of lactation and BCS had no effect. Dry cows had higher levels of T-GSH (938 ± 44 µmol/l) than the fresh (713 ± 46 µmol/l) and peak lactation (785 ± 45 µmol/l) cows. The fresh cows had significantly lower concentrations of GSH (618 ± 44 µmol/l) than the peak lactation (719 ± 46 µmol/l) and dry cows (827 ± 43 µmol/l). On the basis of a regression analysis, blood glutathione was affected mainly by the liver function and energy metabolism. Glutathione as the marker of oxidation stress seems to be a promising tool in monitoring the health and welfare of the herd, yet intensive research in this field remains necessary.
- Klíčová slova
- antioxidant defence, lactation period, liver metabolism, spectrophotometric method,
- Publikační typ
- časopisecké články MeSH
Selenium is an essential trace element important for many physiological processes, especially for the functions of immune and reproductive systems, metabolism of thyroid hormones, as well as antioxidant defense. Selenium deficiency is usually manifested by an increased incidence of retention of placenta, metritis, mastitis, aborts, lowering fertility and increased susceptibility to infections. In calves, lambs and kids, the selenium deficiency demonstrates by WMD (white muscle disease), in foals and donkey foals, it is associated with incidence of WMD and yellow fat disease, and in pigs it causes VESD (vitamin E/selenium deficiency) syndrome. The prevention of these health disorders can be achieved by an adequate selenium supplementation to the diet. The review summarizes the survey of knowledge on selenium, its biological significance in the organism, the impact of its deficiency in mammalian livestock (comparison of ruminants vs. non-ruminants, herbivore vs. omnivore) and possibilities of its peroral administration. The databases employed were as follows: Web of Science, PubMed, MEDLINE and Google Scholar.
- Klíčová slova
- antioxidant, donkeys, horses, metallomics, oxidative stress, ruminants, selenium,
- MeSH
- lidé MeSH
- potravní doplňky MeSH
- savci metabolismus MeSH
- selen nedostatek metabolismus fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- selen MeSH
Catecholamines may undergo iron-promoted oxidation resulting in formation of reactive intermediates (aminochromes) capable of redox cycling and reactive oxygen species (ROS) formation. Both of them induce oxidative stress resulting in cellular damage and death. Iron chelation has been recently shown as a suitable tool of cardioprotection with considerable potential to protect cardiac cells against catecholamine-induced cardiotoxicity. However, prolonged exposure of cells to classical chelators may interfere with physiological iron homeostasis. Prochelators represent a more advanced approach to decrease oxidative injury by forming a chelating agent only under the disease-specific conditions associated with oxidative stress. Novel prochelator (lacking any iron chelating properties) BHAPI [(E)-Ń-(1-(2-((4-(4,4,5,5-tetramethyl-1,2,3-dioxoborolan-2-yl)benzyl)oxy)phenyl)ethylidene) isonicotinohydrazide] is converted by ROS to active chelator HAPI with strong iron binding capacity that efficiently inhibits iron-catalyzed hydroxyl radical generation. Our results confirmed redox activity of oxidation products of catecholamines isoprenaline and epinephrine, that were able to activate BHAPI to HAPI that chelates iron ions inside H9c2 cardiomyoblasts. Both HAPI and BHAPI were able to efficiently protect the cells against intracellular ROS formation, depletion of reduced glutathione and toxicity induced by catecholamines and their oxidation products. Hence, both HAPI and BHAPI have shown considerable potential to protect cardiac cells by both inhibition of deleterious catecholamine oxidation to reactive intermediates and prevention of ROS-mediated cardiotoxicity.
- Klíčová slova
- BHAPI, Cardiotoxicity, Catecholamines, HAPI, Iron chelation, Prochelator,
- MeSH
- adrenalin antagonisté a inhibitory toxicita MeSH
- biokatalýza MeSH
- buněčné linie MeSH
- chelátory železa farmakologie MeSH
- glutathion metabolismus MeSH
- hydroxylový radikál metabolismus MeSH
- isoprenalin antagonisté a inhibitory toxicita MeSH
- kardiotonika farmakologie MeSH
- katecholaminy antagonisté a inhibitory toxicita MeSH
- krysa rodu Rattus MeSH
- kyseliny boronové farmakologie MeSH
- lidé MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- oxidační stres účinky léků MeSH
- prekurzory léčiv farmakologie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- semikarbazony farmakologie MeSH
- sloučeniny boru farmakologie MeSH
- železo chemie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- adrenalin MeSH
- chelátory železa MeSH
- glutathion MeSH
- hydroxylový radikál MeSH
- isoprenalin MeSH
- kardiotonika MeSH
- katecholaminy MeSH
- kyseliny boronové MeSH
- N'-(1-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyloxy)phenyl)ethylidene)isonicotinohydrazide MeSH Prohlížeč
- prekurzory léčiv MeSH
- reaktivní formy kyslíku MeSH
- semikarbazony MeSH
- sloučeniny boru MeSH
- železo MeSH
Anthracyclines (such as doxorubicin or daunorubicin) are among the most effective anticancer drugs, but their usefulness is hampered by the risk of irreversible cardiotoxicity. Dexrazoxane (ICRF-187) is the only clinically approved cardioprotective agent against anthracycline cardiotoxicity. Its activity has traditionally been attributed to the iron-chelating effects of its metabolite with subsequent protection from oxidative stress. However, dexrazoxane is also a catalytic inhibitor of topoisomerase II (TOP2). Therefore, we examined whether dexrazoxane and two other TOP2 catalytic inhibitors, namely sobuzoxane (MST-16) and merbarone, protect cardiomyocytes from anthracycline toxicity and assessed their effects on anthracycline antineoplastic efficacy. Dexrazoxane and two other TOP2 inhibitors protected isolated neonatal rat cardiomyocytes against toxicity induced by both doxorubicin and daunorubicin. However, none of the TOP2 inhibitors significantly protected cardiomyocytes in a model of hydrogen peroxide-induced oxidative injury. In contrast, the catalytic inhibitors did not compromise the antiproliferative effects of the anthracyclines in the HL-60 leukemic cell line; instead, synergistic interactions were mostly observed. Additionally, anthracycline-induced caspase activation was differentially modulated by the TOP2 inhibitors in cardiac and cancer cells. Whereas dexrazoxane was upon hydrolysis able to significantly chelate intracellular labile iron ions, no such effect was noted for either sobuzoxane or merbarone. In conclusion, our data indicate that dexrazoxane may protect cardiomyocytes via its catalytic TOP2 inhibitory activity rather than iron-chelation activity. The differential expression and/or regulation of TOP2 isoforms in cardiac and cancer cells by catalytic inhibitors may be responsible for the selective modulation of anthracycline action observed.
- MeSH
- antracykliny farmakologie MeSH
- biokatalýza účinky léků MeSH
- buněčný cyklus účinky léků MeSH
- daunomycin farmakologie MeSH
- dexrazoxan farmakologie MeSH
- DNA-topoisomerasy typu II metabolismus MeSH
- doxorubicin farmakologie MeSH
- glutathion metabolismus MeSH
- glutathiondisulfid metabolismus MeSH
- HL-60 buňky MeSH
- inhibitory topoisomerasy II farmakologie MeSH
- kardiomyocyty cytologie účinky léků metabolismus MeSH
- kaspasy metabolismus MeSH
- krysa rodu Rattus MeSH
- kultivované buňky MeSH
- lékové interakce MeSH
- lidé MeSH
- novorozená zvířata MeSH
- piperaziny farmakologie MeSH
- potkani Wistar MeSH
- proliferace buněk účinky léků MeSH
- průtoková cytometrie MeSH
- thiobarbituráty farmakologie MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antracykliny MeSH
- daunomycin MeSH
- dexrazoxan MeSH
- DNA-topoisomerasy typu II MeSH
- doxorubicin MeSH
- glutathion MeSH
- glutathiondisulfid MeSH
- inhibitory topoisomerasy II MeSH
- kaspasy MeSH
- merbarone MeSH Prohlížeč
- piperaziny MeSH
- sobuzoxane MeSH Prohlížeč
- thiobarbituráty MeSH
BACKGROUND AND PURPOSE: The anticancer drugs doxorubicin and bleomycin are well-known for their oxidative stress-mediated side effects in heart and lung, respectively. It is frequently suggested that iron is involved in doxorubicin and bleomycin toxicity. We set out to elucidate whether iron chelation prevents the oxidative stress-mediated toxicity of doxorubicin and bleomycin and whether it affects their antiproliferative/proapoptotic effects. EXPERIMENTAL APPROACH: Cell culture experiments were performed in A549 cells. Formation of hydroxyl radicals was measured in vitro by electron paramagnetic resonance (EPR). We investigated interactions between five iron chelators and the oxidative stress-inducing agents (doxorubicin, bleomycin and H(2)O(2)) by quantifying oxidative stress and cellular damage as TBARS formation, glutathione (GSH) consumption and lactic dehydrogenase (LDH) leakage. The antitumour/proapoptotic effects of doxorubicin and bleomycin were assessed by cell proliferation and caspase-3 activity assay. KEY RESULTS: All the tested chelators, except for monohydroxyethylrutoside (monoHER), prevented hydroxyl radical formation induced by H(2)O(2)/Fe(2+) in EPR studies. However, only salicylaldehyde isonicotinoyl hydrazone and deferoxamine protected intact A549 cells against H(2)O(2)/Fe(2+). Conversely, the chelators that decreased doxorubicin and bleomycin-induced oxidative stress and cellular damage (dexrazoxane, monoHER) were not able to protect against H(2)O(2)/Fe(2+). CONCLUSIONS AND IMPLICATIONS: We have shown that the ability to chelate iron as such is not the sole determinant of a compound protecting against doxorubicin or bleomycin-induced cytotoxicity. Our data challenge the putative role of iron and hydroxyl radicals in the oxidative stress-mediated cytotoxicity of doxorubicin and bleomycin and have implications for the development of new compounds to protects against this toxicity.
- MeSH
- aldehydy farmakologie MeSH
- apoptóza účinky léků MeSH
- bleomycin toxicita MeSH
- časové faktory MeSH
- chelátory železa chemie farmakologie MeSH
- deferoxamin farmakologie MeSH
- doxorubicin toxicita MeSH
- elektronová paramagnetická rezonance MeSH
- hydrazony farmakologie MeSH
- isoniazid analogy a deriváty farmakologie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory plic metabolismus patologie MeSH
- oxidační stres účinky léků MeSH
- peroxid vodíku chemie MeSH
- peroxidace lipidů účinky léků MeSH
- proliferace buněk účinky léků MeSH
- protinádorová antibiotika toxicita MeSH
- pyridoxal analogy a deriváty farmakologie MeSH
- razoxan farmakologie MeSH
- sloučeniny železa chemie metabolismus MeSH
- viabilita buněk účinky léků MeSH
- volné radikály chemie MeSH
- železo chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- aldehydy MeSH
- bleomycin MeSH
- chelátory železa MeSH
- deferoxamin MeSH
- doxorubicin MeSH
- Fenton's reagent MeSH Prohlížeč
- hydrazony MeSH
- isoniazid MeSH
- peroxid vodíku MeSH
- protinádorová antibiotika MeSH
- pyridoxal isonicotinoyl hydrazone MeSH Prohlížeč
- pyridoxal MeSH
- razoxan MeSH
- salicylaldehyde isonicotinoyl hydrazone MeSH Prohlížeč
- sloučeniny železa MeSH
- volné radikály MeSH
- železo MeSH
