BACKGROUND AND OBJECTIVES: Organophosphate (OPs) anticholinesterases are one of the main groups of pesticides used in agriculture. Harmful effects of OPs on health have been attributed primarily for irreversible inhibition of acetylcholinesterase (AChE) at nerve synapse. However, studies have shown that inhibition of AChE alone cannot explain all the maladies encountered in prolonged exposure to OPs. Predisposition to population heterogeneity and irregularities in various biochemicals like paraoxonases and inflammatory biochemicals are the possible affects of OPs long term exposure that may lead to sequels of diseases and are less addressed in literature. The study was aimed to assess the cholinergic enzymes (AChE and BChE), PON1, and inflammatory markers (IL1β, IL6, TNFα, CRP, Apo AI, Apo B) and determine the toxicogenetics association of PON1 gene (rs 662 and rs 85456) to chronically OPs exposed groups from Pakistan and Cameroon. MATERIALS AND METHODS: AChE, BChE and PON1 were measured by colorimetric method using spectrophotometry. Inflammatory markers were determined by Elisa assay. PCR-restriction fragment length polymorphism (PCR-RFLP) using salting out method was employed for SNP genotyping. RESULTS: The results revealed the significant (p ≤ 0.05) inhibition of cholinergic enzymes PON 1 was found to be 6.91 ng/mL±1.03 and 2.84 ng/mL±1.40 (mean ± SD) in Pakistan and Cameroon groups respectively. IL6, TNFα, CRP were increased and Apo AI was less while Apo B was increased in OP exposed groups in both population groups. SNPs analysis of PON1 showed significant differences in allelic and genotype frequencies of OPs exposed and non-exposed groups. CONCLUSIONS: PON1 was noticeably less in Cameroonian than Pakistani, albeit both groups have significant decrease in PON1 actity. In addition, the study concludes that OPs induce low grade inflammation, an aetiology of many diseases. Selected PON1 SNPs analysis showed a significant toxicogenetics association with OPs exposure marker enzymes. The results of this study may help in regulation of usage of OPs anticholinesterases in different populations. The study will further open new avenues in toxicogenetic and exploration of SNPs based strategies on organophosphate intoxication.
- MeSH
- acetylcholinesterasa genetika MeSH
- aryldialkylfosfatasa genetika MeSH
- lidé MeSH
- organofosfáty MeSH
- organofosforové sloučeniny * MeSH
- pesticidy * toxicita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Pákistán MeSH
Cíl studie: Posoudit vliv malnutrice u pacientů s karcinomem pankreatu (PC) na míru oxidačního stresu a na antioxidační systém organismu. Typ studie: Observační, strukturálně vyvážená studie případů a kontrol. Název a sídlo pracoviště: IV. Interní klinika, 1. LF UK a VFN v Praze, U Nemocnice 2, 128 01 Praha 2, Česká republika Materiál a metody: Do studie bylo zařazeno 68 pacientů (M/F = 36/32) s PC, kteří byli podle indexu NRI (nutrition risk index) rozděleni do dvou skupin na pacienty se středně těžkou až těžkou malnutricí (PC-MAL) a pacienty s lehkou malnutricí či bez malnutrice (PC-NOR). Každá skupina čítala 34 osob (M/F = 18/16) a mezi skupinami nebyl signifikantní rozdíl ve věku. Dále byla do studie zařazena na základě věku a pohlaví spárovaná kontrolní skupina (CON). Sledovaným subjektům byly odebírány vzorky po celonočním lačnění a kromě základních klinických a biochemických parametrů byly stanovovány markery oxidačního stresu (konjugované dieny v precipitovaných LDL; CD/LDL a oxidované LDL; ox-LDL/LDL), aktivity antioxidačních enzymů a koncentrace redukovaného glutathionu (GSH). Ke statistickému zpracování výsledků byl použit program STATISTICA (Stat Soft, CZ). Výsledky: Výsledky naší studie potvrzují zvýšený oxidační stres u pacientů s PC a to zvýšenými hladinami ox-LDL/LDL a CD/ LDL v porovnání s CON (p < 0,01). Signifikantně vyšší hladiny těchto markerů měli pacienti s malnutricí než bez malnutrice. Pozorovány byly rovněž výrazné změny v antioxidačním systému u pacientů s PC; kteří oproti CON skupině měli sníženou aktivitu katalázy (CAT, p < 0,01) glutationperoxidázy (p < 0,01), arylesterázovou (PON-A) i laktonázovou aktivitu (PON-L) paraoxonázy (p < 0,01) a koncentraci redukovaného glutathionu (p < 0,001) a zvýšené hladiny sérového amyloidu A (SAA, p < 0,001). Ovlivnění aktivit CAT, PON-A a PON-L a hladiny SAA bylo signifikantně větší u pacientů s podvýživou oproti PC pacientům bez příznaků malnutrice. Závěr: V této studii bylo prokázáno prohloubení oxidačního stresu a výraznější ovlivnění funkce antioxidačního systému organismu pacientů vlivem malnutrice.
Objective: To assess the influence of malnutrition in patients with pancreatic carcinoma (PC) on the oxidative stress and antioxidant system. Design: Observation, matched case-control study. Settings: This study was conducted at the 4th Department of Internal Medicine of General University Hospital in Prague, U Nemocnice 2, 128 01 Prague 2, Czech Republic Material and methods: In to our study 68 patients (M/F = 36/32) with PC were included and divided according to the nutrition risk index into two groups – patients with moderate or severe malnutrition (PC-MAL) and mild or no malnutrition (PCNOR). In both groups there were 34 patients (M/F = 18/16) with no difference in age between both groups. Furthermore, group of 34 sex- and age-matched healthy controls (CON) were enrolled into the study. The samplings were taken after overnight fast and apart from basic clinical and biochemical parameters markers of oxidative stress (level of conjugated dienes in precipitated LDL, CD/LDL and oxidized LDL, ox-LDL/LDL), activities of antioxidant enzymes and concentration of reduced glutathione (GSH) were assessed. For all statistical analysis the statistical program STATISTICA (Stat Soft, CZ) was used. Results: In our study we confirmed increased oxidative stress in PC, with higher levels of ox-LDL/LDL and CD/LDL compared to CON (p < 0.01). Significantly higher levels of these markers were in patients with malnutrition then without malnutrition. We observed also changes in antioxidant system of PC patients – these patients had decreased activity of catalase (CAT, p < 0.01), glutathione peroxidase (p < 0.01), arylesterase (PON-A) and also lactonase activity (PON-L) of paraoxonase (p < 0.01) and concentration of GSH (p < 0.001) and higher levels of serum amyloid A (SAA, p < 0.001). The changes in CAT, PON-A, PON-L and SAA levels were significantly higher in PC patients with malnutrition then without. Conclusion: In this study we proved the deepening of oxidative stress and the strongly impaired function of antioxidant system in PC patients due to malnutrition.
- MeSH
- aryldialkylfosfatasa analýza krev MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- nádory slinivky břišní * komplikace patofyziologie MeSH
- oxidační stres * MeSH
- podvýživa MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Beside the key inhibition of acetylcholinesterase (AChE), involvement of oxidative stress in organophosphate (OP)-induced toxicity has been supported by experimental and human studies. On the other hand, according to our best knowledge, possible antioxidant properties of oximes, the only causal antidotes to OP-inhibited AChE, have been examined only by a few studies. Thus, we have determined the effect of four conventional (obidoxime, trimedoxime, pralidoxime, asoxime) and two promising experimental oximes (K027, K203) on dichlorvos (DDVP)-induced oxidative changes in vivo. Wistar rats (5/group) were treated with oxime (5% LD50 i.m) immediately after DDVP challenge (75% LD50 s.c). Oxidative stress biomarkers were determined in plasma and brain 60 min after the treatment: prooxidative-superoxide anion (O2·-) and total oxidative status (TOS); antioxidative-superoxide dismutase (SOD), total thiol (SH) groups, total antioxidant status (TAS) and paraoxonase (PON1); tissue oxidative stress burden-prooxidative-antioxidative balance (PAB) and oxidative stress index (OSI); oxidative tissue damage-malondialdehyde (MDA) and advanced oxidation protein products (AOPP). All oximes were able to attenuate DDVP-induced oxidative stress in rat plasma and brain. Changes of determined parameters in brain were not as prominent as it was seen in plasma. Based on OSI, better abilities of oxime K027, K203 and obidoxime to maintain DDVP-induced oxidative stress in rat brain were shown as compared to trimedoxime, pralidoxime and asoxime. Oximes can influence the complex in vivo redox processes that might contribute to their overall therapeutic efficacy. Further research is needed to understand the underlying molecular mechanisms involved in this phenomenon.
- MeSH
- aryldialkylfosfatasa krev MeSH
- biologické markery krev MeSH
- cholinesterasové inhibitory farmakologie MeSH
- dichlorvos toxicita MeSH
- krysa rodu rattus MeSH
- malondialdehyd krev MeSH
- mozek účinky léků MeSH
- obidoxim chlorid farmakologie MeSH
- otrava organofosfáty farmakoterapie MeSH
- oxidační stres účinky léků MeSH
- oximy farmakologie MeSH
- pralidoximové sloučeniny MeSH
- pyridinové sloučeniny farmakologie MeSH
- superoxiddismutasa krev MeSH
- trimedoxim farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Activated platelets and glycated lipoproteins are responsible for atherothrombosis in diabetics. Melatonin and native high-density lipoproteins are crucial in the preservation of pro/oxidant-antioxidant balance. The aim of the present study was to investigate the in vitro effects of native high-density lipoproteins and melatonin on altering the platelet response induced by glycated lipoproteins. Low-density lipoproteins and high-density lipoproteins were purified from plasma by ultracentrifugation and were glycated with glucose for three weeks. After incubation with or without melatonin/or native highdensity lipoproteins, low-density lipoproteins, glycated low-density lipoproteins/glycated high-density lipoproteins were added to ADP-induced platelets. Oxidative parameters, caspase-3/9 and nitric oxide levels were measured spectrophotometrically; CD62-P/ annexin-V expression was determined by flow cytometry. In glycated low-density lipoprotein/glycated high-density lipoprotein-treated groups, platelet malondialdehyde/ protein carbonyl, P-selectin, annexin-V, caspase-3/9 levels were increased (ranging from P < 0.001 to P < 0.01); glutathione and nitric oxide levels were reduced (ranging from P < 0.001 to P < 0.01). In glycated low-density lipoprotein/glycated high-density lipoprotein-treated groups, melatonin treatment reduced malondialdehyde, protein carbonyl, CD62-P, annexin-V and caspase-3/9 (P < 0.001, P < 0.01) levels and elevated nitric oxide (only glycated low-density lipoproteins). In glycated low-density lipoprotein/glycated high-density lipoprotein-treated groups, native high-density lipoprotein treatment reduced malondialdehyde, protein carbonyl, annexin-V, caspase-3/9 levels (P < 0.001, P < 0.01) and increased glutathione; nitric oxide levels (only with gly-HDL). Both melatonin and high-density lipoproteins should be regarded as novel promising mechanism-based potential therapeutic targets to prevent atherothrombosis in diabetics.
- MeSH
- apoptóza účinky léků MeSH
- aryldialkylfosfatasa metabolismus MeSH
- dospělí MeSH
- glutathion metabolismus MeSH
- glykosylace účinky léků MeSH
- karbonylace proteinů MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipoproteiny HDL farmakologie MeSH
- malondialdehyd metabolismus MeSH
- melatonin farmakologie MeSH
- oxid dusnatý metabolismus MeSH
- oxidace-redukce MeSH
- oxidační stres účinky léků MeSH
- trombocyty účinky léků MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Organophosphorus compounds (OP) are part of a group of compounds that may be hazardous to health. They are called neurotoxic agents because of their action on the nervous system, inhibiting the acetylcholinesterase (AChE) enzyme and resulting in a cholinergic crisis. Their high toxicity and rapid action lead to irreversible damage to the nervous system, drawing attention to developing new treatment methods. The diisopropyl fluorophosphatase (DFPase) enzyme has been considered as a potent biocatalyst for the hydrolysis of toxic OP and has potential for bioremediation of this kind of intoxication. In order to investigate the degradation process of the nerve agents Tabun, Cyclosarin and Soman through the wild-type DFPase, and taking into account their stereochemistry, theoretical studies were carried out. The intermolecular interaction energy and other parameters obtained from the molecular docking calculations were used to construct a data matrix, which were posteriorly treated by statistical analyzes of chemometrics, using the PCA (Principal Components Analysis) multivariate analysis. The analyzed parameters seem to be quite important for the reaction mechanisms simulation (QM/MM). Our findings showed that the wild-type DFPase enzyme is stereoselective in hydrolysis, showing promising results for the catalytic degradation of the neurotoxic agents under study, with the degradation mechanism performed through two proposed pathways.
Cíl studie: Paraoxonasa 1 (PON1) je antioxidační enzym s širokým spektrem fyziologických úloh – jednou z důležitých funkcí PON1 je její schopnost inhibovat LDL-lipidovou peroxidaci a inaktivovat oxidované fosfolipidy. Cílem této studie bylo sledovat aktivitu PON1 a hladinu konjugovaných dienů v precipitovaných LDL částicích (CD/LDL) u subjektů s různým počtem splněných kritérií metabolického syndromu (MetS). Typ studie: Observační. Název a sídlo pracoviště: IV. Interní klinika 1. Lékařské fakulty Univerzity Karlovy a Všeobecné fakultní nemocnice v Praze. Materiál a metody: Do studie bylo celkem zařazeno 254 subjektů (188 žen/166 mužů) rozdělených do šesti skupin, a to podle počtu splněných kritérií (podle počtu přítomných komponent) metabolického syndromu. Všechny skupiny byly spárovány na základě věku. Hlavními sledovanými parametry byla aktivita PON1 a koncentrace CD/LDL. Měření obou těchto parametrů bylo prováděno spektrofotometrickými metodami. Výsledky: Pacienti, kteří splňovali všech pět kritérií MetS měli signifikantně snížené aktivity PON1 ve srovnání se skupinami pacientů s žádným až třemi parametry MetS (p < 0.05). Hladina CD/LDL byla naopak u pacientů, kteří splňovali čtyři nebo všech pět kritérií MetS signifikantně zvýšena ve srovnání s ostatními skupinami (p < 0.001). Závěr: Naše studie ukázala, že aktivita PON1 je ve značné míře ovlivňována koncentrací HDL-C a apoA1 a dále, že aktivity PON1 jsou snížené a naopak hladiny CD/LDL zvýšené hlavně u pacientů, kteří splňují všech pět kritérií metabolického syndromu.
Objective: Paraoxonase 1 is an antioxidant enzyme with a variety of physiological roles – one of them is the inhibition of LDL (low-density lipoprotein) lipid peroxidation and inactivation of LDL-derived oxidized phospholipids. The aim of this study was to investigate the PON1 activity and levels of conjugated dienes in precipitated LDL (CD/LDL) in subjects, who fulfill different numbers of metabolic syndrome (MetS) criteria. Design: Cross-sectional study Settings: 4 th Department of Internal Medicine, 1 st Faculty of Medicine, Charles University and General University Hospital Prague Material and methods: The population under study consisted of 354 Caucasian subjects (188 females/166 males) divided into 6 groups according to the number of presented components of metabolic syndrome. All groups were age matched. The activity of paraoxonase 1 and concentration of conjugated dienes in precipitated LDL (CD/LDL) were both assessed spectrophotometrically. Results: The activity of PON1 was significantly decreased in subjects with all 5 components of MetS in comparison with those with 0 to 3 components of MetS (p < 0.05). The concentrations of CD/LDL were increased in subjects with 4 or 5 components of MetS compared to subjects with 0-3 components of MetS (p < 0.001). Conclusion: As was shown in this study, the levels of PON1 are extensively affected by the concentration of HDL-C and ApoA1. PON1 activity is depressed and CD/LDL levels are increased mainly in subjects who fulfill all five criteria of MetS
- Klíčová slova
- konjugované dieny,
- MeSH
- aryldialkylfosfatasa * analýza fyziologie MeSH
- lipoproteiny LDL analýza MeSH
- metabolický syndrom krev MeSH
- spektrofotometrie MeSH
- Publikační typ
- pozorovací studie MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- paraoxonáza, snížená aktivita paraoxonázy, koncentrace sérového amyloidu A, zvýšená hladina koncentrace amyloidu A,
- MeSH
- aryldialkylfosfatasa * analýza farmakologie fyziologie krev metabolismus MeSH
- biochemická analýza krve * MeSH
- dospělí MeSH
- duktální karcinom pankreatu * diagnóza patofyziologie MeSH
- duktální karcinom prsu * diagnóza patofyziologie MeSH
- klinické chemické testy * MeSH
- klinické laboratorní techniky * MeSH
- klinické zkoušky jako téma metody statistika a číselné údaje MeSH
- lidé MeSH
- sérový amyloid A * analýza farmakologie fyziologie metabolismus MeSH
- zánět * diagnóza MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
Cíl studie: Na základě soudobých studií podat přehled o hlavních biologických funkcích lipoproteinů o vysoké hustotě (HDL), zejména ve vztahu k reverznímu transportu cholesterolu a k jejich protizánětlivému působení. Popsat pravděpodobné mechanismy vzniku dysfunkčních prozánětlivých HDL a uvést některé parametry asociované s tímto procesem. Podat přehled o laboratorních metodách stanovení kvantitativních, strukturních a funkčních vlastností HDL, včetně moderních metod založených na hmotové spektrometrii. Typ studie: přehledový článek Závěr: V případě systémového zánětu a/nebo oxidačního stresu dochází ke vzniku dysfunkčních HDL akumulujících oxidanty. Probíhá strukturní modifikace apolipoproteinu AI, což vede mimo jiné k inhibici reverzního transportu cholesterolu a tvorbě prozánětlivých HDL. Na ztrátě příznivých vlastností HDL se podílí modifikace proteinové i lipidové složky HDL. Izolované měření HDL cholesterolu nemusí u některých syndromů bezvýhradně korelovat s mírou kardiovaskulárního rizika a v některých situacích je vhodné stanovit markery mapující strukturu a funkci HDL.
Objective: On the basis of recent studies to make an overview concerning the crucial biological functions of high density lipoproteins (HDL), with emphasis on the role in reverse cholesterol transport and their antiinflammatory traits. The aim was to describe probable mechanisms of dysfunctional proinflammatory HDL formation with introduction some of associated parameters. To present laboratory methods for determination of quantitative, structural and functional qualities of HDL, including advanced mass spectrometry techniques. Study design: review Conclusion: In the case of systemic inflammation and/or oxidative stress, the formation of dysfunctional HDL accumulating oxidants takes place, including apo AI structural modifications. This process can lead to the inhibition of reverse cholesterol transport and proinflammatory HDL generation, among others. Loss of beneficial qualities results from modification of both lipid and protein components of HDL. In some cases, an isolated quantitative measurement of HDL cholesterol may not fully correlate with cardiovascular risk and it is eligible to determine some of structural and/or functional markers of HDL.
- MeSH
- adiponektin analýza terapeutické užití MeSH
- apolipoproteiny analýza MeSH
- aryldialkylfosfatasa analýza terapeutické užití MeSH
- dospělí MeSH
- HDL-cholesterol analýza MeSH
- hmotnostní spektrometrie MeSH
- ischemická choroba srdeční diagnóza prevence a kontrola MeSH
- kardiovaskulární nemoci diagnóza prevence a kontrola MeSH
- klinické laboratorní techniky metody využití MeSH
- lidé MeSH
- lipoproteiny HDL * fyziologie klasifikace MeSH
- peroxidasa analýza terapeutické užití MeSH
- proteomika * MeSH
- senioři MeSH
- transportní proteiny pro estery cholesterolu MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
OBJECTIVE: In the pathogenesis of the metabolic syndrome (MetS), an increase of oxidative stress could play an important role which is closely linked with insulin resistance, endothelial dysfunction, and chronic inflammation. The aim of our study was to assess several parameters of the antioxidant status in MetS. METHODS: 40 subjects with MetS and 40 age- and sex-matched volunteers without MetS were examined for activities of superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase 1 (GPX1), glutathione reductase (GR), paraoxonase1 (PON1), concentrations of reduced glutathione (GSH), and conjugated dienes in low-density lipoprotein (CD-LDL). RESULTS: Subjects with MetS had higher activities of CuZnSOD (p < 0.05) and GR (p < 0.001), higher concentrations of CD-LDL (p < 0.001), lower activities of CAT (p < 0.05) and PON1 (p < 0.05), and lower concentrations of GSH (p < 0.05), as compared with controls. Activity of GPX1 was not significantly changed. CONCLUSIONS: Our results implicated an increased oxidative stress in MetS and a decreased antioxidative defense that correlated with some laboratory (triglycerides, high-density lipoprotein cholesterol (HDL-C)) and clinical (waist circumference, blood pressure) components of MetS.
- MeSH
- antioxidancia analýza MeSH
- aryldialkylfosfatasa krev MeSH
- biologické markery krev MeSH
- enzymy krev MeSH
- glutathion krev MeSH
- glutathionperoxidasa krev MeSH
- glutathionreduktasa krev MeSH
- katalasa krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipoproteiny LDL krev MeSH
- metabolický syndrom krev diagnóza enzymologie MeSH
- oxidační stres MeSH
- studie případů a kontrol MeSH
- superoxiddismutasa krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
