The widely used insecticide chlorpyrifos (CP) is known to inhibit acetylcholinesterase (AChE) activity attributed to result in various neurological disorders and acetylcholine-dependent organ functions including heart, skeletal muscle, lung, gastrointestinal tract, and central nervous systems. Enzyme reactivators, such as oximes, are known to restore AChE activity and mitigate adverse effects. The identification of compounds that reactivate AChE constitute agents with important therapeutic beneficial effects in cases of pesticide poisoning. However, the screening of novel drugs using traditional models may raise ethical concerns. This study aimed to investigate the potential of Drosophila melanogaster as a model organism for screening AChE reactivators, with a focus on organophosphate poisoning. The efficacy of several oximes, including pralidoxime, trimedoxime, obidoxime, methoxime, HI-6, K027, and K048, against CP-induced AChE activity inhibition in D. melanogaster was determined in silico, in vitro, and in vivo experiments. Molecular docking studies indicated a strong interaction between studied oximes and the active-site gorge of AChE. Data showed that selected oximes (100 μM) are effective in the reactivation of AChE inhibited by CP (10 μM) in vitro. Finally, in vivo investigations demonstrated that selected oximes, pralidoxime and K048 (1.5 ppm), reversed the locomotor deficits, inhibition of AChE activity as well as lowered the mortality rates induced by CP (0.75 ppm). Our findings contribute to utilization of D. melanogaster as a robust model for determination of actions of identified new AChE inhibitory agents with more effective therapeutic properties that those currently in use in the clinical practice in treatment of AChE associated disorders.
- Klíčová slova
- Drosophila melanogaster, Insecticides, acetylcholinesterase inhibition, locomotor, molecular docking, organophosphates, oximes, risk assessment, screening,
- MeSH
- acetylcholinesterasa * metabolismus MeSH
- cholinesterasové inhibitory toxicita MeSH
- Drosophila melanogaster * účinky léků enzymologie MeSH
- dursban * toxicita MeSH
- insekticidy toxicita MeSH
- modely u zvířat MeSH
- oximy * farmakologie MeSH
- reaktivátory cholinesterázy * farmakologie MeSH
- simulace molekulového dockingu * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- acetylcholinesterasa * MeSH
- cholinesterasové inhibitory MeSH
- dursban * MeSH
- insekticidy MeSH
- oximy * MeSH
- reaktivátory cholinesterázy * MeSH
Results of a number of studies indicate that electroplaters have increased cancer risks as a consequence of exposure to genotoxic metals such as chromium (VI) and nickel. These effects may be due to induction of damage of the genetic material which plays a key role in the etiology of cancer, and it was found that workers in galvanization factories exhibited increased levels of DNA damage. The aim of the present study was to investigate genetic stability in workers of a bright plating factory who are exposed to chromium (Cr) and cobalt (Co). Exfoliated cells were collected from the buccal and nasal mucosa of workers (n = 42) and matched controls (n = 43) and analyzed for induction of micronuclei (MN) which are formed as a consequence of chromosomal aberrations. In addition, other nuclear anomalies namely nuclear buds (Nbuds) which are formed as a consequence of gene amplification and markers indicating different stages of cell death (condensed chromatin, karyorrhexis, karyolysis, and pyknosis) were also assessed. No evidence was noted for induction of MN, but significantly increased rates of Nbuds in cells from both, buccal and nasal mucosa, were found. Parameters which are indicative for cytotoxic effects were more pronounced in nasal cells and rose with duration of employment period. Overall, our findings indicated that no apparent chromosomal damage occurred in bright electroplaters. However, data demonstrated that acute cytotoxic effects may lead to inflammations and/or lesions in epithelia of the respiratory tract of the workers.
- MeSH
- buněčná smrt účinky léků MeSH
- buněčné jádro účinky léků MeSH
- chrom toxicita MeSH
- dospělí MeSH
- kobalt toxicita MeSH
- lidé MeSH
- lidské chromozomy účinky léků MeSH
- mikrojádra chromozomálně defektní chemicky indukované MeSH
- nosní sliznice účinky léků MeSH
- pokovování galvanické * MeSH
- pracovní expozice škodlivé účinky MeSH
- ústní sliznice účinky léků MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chrom MeSH
- kobalt MeSH
The widespread use of agrochemicals is detrimental to the environment and may exert harmful effects on human health. The consumer demand for organic food plants has been increasing. There is thus a rising need for alternatives to agrochemicals that can foster sustainable plant production. The aim of this study was to evaluate the potential use of an arbuscular mycorrhizal (AM) fungus as an alternative to application of chemical fertilizer for improving growth performance of the medicinal and aromatic plant Coriandrum sativum. Plants were inoculated with the AM fungus Rhizophagus irregularis BEG163 and/or supplemented with a commercial chemical fertilizer (Plant Marvel, Nutriculture Bent Special) in agricultural soil. Plant growth, nutrition, and development of AM fungus were assessed. Plants inoculated with R. irregularis and those supplemented with chemical fertilizer displayed significantly improved growth performances when compared with controls. There were no significant differences in total fresh weight between plants inoculated with R. irregularis or those supplemented with chemical fertilizer. Leaf chlorophyll a + b (82%), shoot nitrogen (44%), phosphorus (254%), and potassium (27%) concentrations increased in plants inoculated with R. irregularis compared to controls. Application of chemical fertilizer inhibited root mycorrhizal colonization and the length of the extraradical mycelium of R. irregularis. Inoculation with R. irregularis was equally or more efficient than application of chemical fertilizer in promoting growth and nutrition of C. sativum. AM fungi may thus contribute to improve biologically based production of food plants and reduce the dependence on agrochemicals in agriculture.
- MeSH
- kořeny rostlin růst a vývoj mikrobiologie fyziologie MeSH
- koriandr růst a vývoj mikrobiologie fyziologie MeSH
- léčivé rostliny růst a vývoj mikrobiologie fyziologie MeSH
- listy rostlin růst a vývoj fyziologie MeSH
- mykorhiza fyziologie MeSH
- průmyslová hnojiva analýza MeSH
- půdní mikrobiologie * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- průmyslová hnojiva MeSH
The exploitation of arbuscular mycorrhizal (AM) fungi has become of great interest in agriculture due to their potential roles in reducing the need for agrochemicals, while improving plant growth and nutrition. Nevertheless, the application of AM fungi by dispersing inocula in granular form to open agricultural fields is not feasible because nontargeted spreading of inocula over large surface areas results in high cost per plant. Seed coating has the potential to significantly reduce the amount of inoculum needed, resulting in cost reduction and increased efficiency. The aim of this study was to assess whether seed coating with AM fungal inoculum is a feasible delivery system for production of common wheat (Triticum aestivum L.). Wheat seeds were coated with inoculum of Rhizophagus irregularis BEG140 and grown under different fertilization conditions: (1) none, (2) partial, or (3) complete. Data indicated that mycorrhizal inoculation via seed coating significantly increased the dry weight of shoot and seed spikes of wheat associated with reduced fertilization. Assessment of nutritional status of wheat showed that plants inoculated with R. irregularis via seed coating displayed enhanced stem concentrations of potassium (K), sulfur (S), and zinc (Zn). There were no significant differences in root colonization between plants conventionally inoculated with R. irregularis in soil and those inoculated via seed coating. Seed coating with AM fungi may be as effective as conventional soil inoculation and may contribute to reduce the utilization of chemical fertilizers. The application of AM via seed coating is proposed as an ecotechnological approach for sustainable agricultural wheat production.
- MeSH
- Glomeromycota fyziologie MeSH
- mykorhiza fyziologie MeSH
- průmyslová hnojiva analýza MeSH
- pšenice růst a vývoj mikrobiologie MeSH
- půdní mikrobiologie * MeSH
- semena rostlinná mikrobiologie fyziologie MeSH
- zemědělství metody MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- průmyslová hnojiva MeSH
Transmissive spongiform encephalopathies (TSE) are neurodegenerative diseases characterized by depositions of abnormally folded prion protein (PrP(TSE)) in brain. PrP(TSE) is at present the only specific biochemical marker of human and animal TSE. As deposits of PrP(TSE) remain in the body for long periods, there is substantial chance of them being nonenzymatically modified by glycation. The detection of glycated PrP(TSE) may have potential to serve as a diagnostic marker. Monoclonal antibodies specific for carboxymethyl lysine/arginine-modified prion protein were prepared. Recombinant human prion protein (rhPrP) was bacterially expressed and purified by affinity chromatography. rhPrP was modified by glyoxylic acid that introduces carboxymethyl groups on lysine and arginine residues present within the molecule of the protein. Modified rhPrP (rhPrP-CML) was used for immunization of 6 mice, and 960 hybridoma cells were prepared. Screening of cell supernatants resulted in the selection of four promising clones. One of them (EM-31) strongly reacts with human and mouse recombinant PrP-CML, and three other clones react also with CML in vitro modified human and mouse brain PrP. Besides possible implication in TSE diagnostics, the antibodies may serve as tolls to advance our knowledge regarding the role of glycation in the prion pathophysiology.
- MeSH
- arginin analogy a deriváty chemie metabolismus MeSH
- glykosylace MeSH
- hybridomy imunologie metabolismus MeSH
- lidé MeSH
- lysin analogy a deriváty chemie metabolismus MeSH
- monoklonální protilátky * imunologie metabolismus MeSH
- mozek imunologie metabolismus MeSH
- myši knockoutované MeSH
- myši transgenní MeSH
- myši MeSH
- peptidy chemie metabolismus MeSH
- prionové nemoci diagnóza imunologie metabolismus MeSH
- priony * chemie metabolismus MeSH
- rekombinantní proteiny chemie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- arginin MeSH
- lysin MeSH
- monoklonální protilátky * MeSH
- N(6)-carboxymethyllysine MeSH Prohlížeč
- peptidy MeSH
- priony * MeSH
- rekombinantní proteiny MeSH
Tabun (O-ethyl-N,N-dimethyl phosphoramidocyanidate) belongs to the group of highly toxic organophosphorus compounds that may be used as chemical warfare agents for military as well as terrorist purposes. Tabun differs from other highly toxic organophosphates by the fact that commonly used antidotes are not able adequately to prevent tabun-induced acute toxic effects. The neuroprotective effects of four bispyridinium oximes (K075, trimedoxime, HI-6, obidoxime) in combination with atropine on rats poisoned with tabun at a sublethal dose (150 microg/kg i.m.; 80% of LD50 value) were studied. Tabun-induced neurotoxicity was monitored using a functional observational battery and automatic measurement of motor activity at 24 h and 7 d following tabun challenge. The results indicated that all tested oximes combined with atropine enabled tabun-poisoned rats to survive 7 d following challenge. Trimedoxime combined with atropine was the most effective antidote in decreasing tabun-induced neurotoxicity in the case of sublethal poisonings among all oximes tested. Due to its neuroprotective effects, trimedoxime may be considered to be more suitable oxime for the antidotal treatment of acute tabun exposure than currently used oximes (obidoxime, HI-6) and the newly synthesized oxime K075.
- MeSH
- antagonisté muskarinových receptorů farmakologie MeSH
- atropin farmakologie MeSH
- chemické bojové látky otrava MeSH
- cholinesterasové inhibitory otrava MeSH
- kombinovaná farmakoterapie MeSH
- krysa rodu Rattus MeSH
- neuroprotektivní látky farmakologie MeSH
- neurotoxické syndromy farmakoterapie MeSH
- organofosfáty MeSH
- otrava organofosfáty * MeSH
- oximy farmakologie MeSH
- potkani Wistar MeSH
- reaktivátory cholinesterázy farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antagonisté muskarinových receptorů MeSH
- atropin MeSH
- chemické bojové látky MeSH
- cholinesterasové inhibitory MeSH
- neuroprotektivní látky MeSH
- organofosfáty MeSH
- oximy MeSH
- reaktivátory cholinesterázy MeSH
- tabun MeSH Prohlížeč
The potency of newly developed asymmetric bispyridinium oximes (K027, K048) in reactivating tabun-inhibited acetylcholinesterase (AChE) and in eliminating tabun-induced acute toxic effects was compared with commonly used oximes (obidoxime, trimedoxime, the oxime HI-6) using in vivo methods. Studies determined the percent of reactivation of tabun-inhibited blood and tissue AChE in poisoned rats and showed that the reactivating efficacy of both newly developed oximes is comparable with obidoxime and trimedoxime, the most efficacious known reactivators of tabun-inhibited AChE. These were also found to be sufficiently efficacious in the elimination of acute lethal toxic effects in tabun-poisoned rats. The oxime HI-6, relatively efficacious against soman, did not seem to be an adequately effective oxime in reactivation of tabun-inhibited AChE and in counteracting acute lethal effects of tabun. In addition, our results confirm that the efficacy of oximes in reactivating tabun-inhibited AChE in blood, diaphragm, and brain correlates with the potency of oximes in protecting rats poisoned with supralethal doses of tabun.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- aktivace enzymů MeSH
- bránice enzymologie MeSH
- chemické bojové látky otrava MeSH
- krysa rodu Rattus MeSH
- mozek enzymologie MeSH
- organofosfáty MeSH
- otrava organofosfáty * MeSH
- otrava farmakoterapie MeSH
- oximy farmakologie MeSH
- potkani Wistar MeSH
- pyridinové sloučeniny farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- 1-(4-hydroxyiminomethylpyridinium)-3-(carbamoylpyridinium) propane dibromide MeSH Prohlížeč
- 1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)butane MeSH Prohlížeč
- acetylcholinesterasa MeSH
- chemické bojové látky MeSH
- organofosfáty MeSH
- oximy MeSH
- pyridinové sloučeniny MeSH
- tabun MeSH Prohlížeč
The efficacy of H oximes (HI-6, HLö-7), the oxime BI-6, and currently used oximes (pralidoxime, obidoxime, trimedoxime) to reactivate acetylcholinesterase inhibited by two nerve agents (tabun, VX agent) was tested in vitro. Both H oximes (HI-6, HLö-7) and the oxime BI-6 were found to be more efficacious reactivators of VX-inhibited acetylcholinesterase than pralidoxime and obidoxime. On the other hand, their potency to reactivate tabun-inhibited acetylcholinesterase was low and did not reach the reactivating efficacy of trimedoxime and obidoxime. Thus, none of these compounds can be considered to be a broad-spectrum reactivator of nerve agent-inhibited acetylcholinesterase in spite of high potency to reactivate acetylcholinesterase inhibited by some nerve agents. More than one oxime may be necessary for the antidotal treatment of nerve agent-exposed individuals.
- MeSH
- acetylcholinesterasa fyziologie MeSH
- antidota farmakologie MeSH
- chemické bojové látky farmakologie MeSH
- cholinesterasové inhibitory farmakologie MeSH
- krysa rodu Rattus MeSH
- mozek účinky léků MeSH
- obidoxim chlorid farmakologie MeSH
- organofosfáty farmakologie MeSH
- organothiofosforové sloučeniny farmakologie MeSH
- oximy farmakologie MeSH
- potkani Wistar MeSH
- pralidoximové sloučeniny farmakologie MeSH
- pyridinové sloučeniny farmakologie MeSH
- pyridiny farmakologie MeSH
- reaktivátory cholinesterázy farmakologie MeSH
- trimedoxim farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- acetylcholinesterasa MeSH
- antidota MeSH
- asoxime chloride MeSH Prohlížeč
- BI 6 MeSH Prohlížeč
- chemické bojové látky MeSH
- cholinesterasové inhibitory MeSH
- HLo 7 MeSH Prohlížeč
- obidoxim chlorid MeSH
- organofosfáty MeSH
- organothiofosforové sloučeniny MeSH
- oximy MeSH
- pralidoxime MeSH Prohlížeč
- pralidoximové sloučeniny MeSH
- pyridinové sloučeniny MeSH
- pyridiny MeSH
- reaktivátory cholinesterázy MeSH
- tabun MeSH Prohlížeč
- trimedoxim MeSH
- VX MeSH Prohlížeč
The potency of newly developed and currently used oximes to reactivate sarin-inhibited acetylcholinesterase was evaluated using in vitro methods. A rat brain homogenate was used as a source of acetylcholinesterase. Significant differences in reactivation potency among all tested oximes were observed. Although the ability of newly developed oximes to reactivate sarin-inhibited acetylcholinesterase does not reach the reactivating potency of the oxime HI-6, the oxime K033 seems to be a more efficacious reactivator of sarin-inhibited acetylcholinesterase than other currently available oximes (pralidoxime, obidoxime) at concentrations (10(-5)-10(-4)M) corresponding to recommended doses in vivo. The results of our study also confirm that the reactivation potency of the tested reactivators depends on many factors, such as (1) the number of pyridinium rings, (2) the number of oxime groups and their position, and (3) the length and the shape of the linkage bridge between pyridinium rings.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- chemické bojové látky toxicita MeSH
- cholinesterasové inhibitory toxicita MeSH
- krysa rodu Rattus MeSH
- kultivované buňky MeSH
- mozek účinky léků enzymologie MeSH
- oximy farmakologie MeSH
- potkani Wistar MeSH
- sarin antagonisté a inhibitory toxicita MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- acetylcholinesterasa MeSH
- chemické bojové látky MeSH
- cholinesterasové inhibitory MeSH
- oximy MeSH
- sarin MeSH
