HI-6 is used as an antidote to nerve agents. It can also act as an antagonist to acetylcholine receptors (AChRs) including the nicotinic receptor, α 7 nAChR which is involved in regulating the immune response through macrophages. This experiment investigated the efficacy of HI-6 to regulate the immune response. Laboratory BALB/c mice received HI-6 and/or keyhole limpet hemocyanin (KLH) as an antigen. Antibody production was investigated after either 21 or 65 days when either single or repeated dose of antigen was applied. We confirmed that HI-6 significantly improved vaccination efficacy when KLH was given in a dose of 1mg/kg. The effect was dose dependent. A combination of HI-6 and KLH produced a vaccination of almost the same efficacy as that for Freund's complete adjuvant. The findings point at the suitability of HI-6 for improving vaccination efficacy at the level of immunity regulation by the nervous system.
- MeSH
- adjuvancia imunologická farmakologie MeSH
- antidota farmakologie MeSH
- ELISA MeSH
- Freundovo adjuvans MeSH
- hemokyanin imunologie MeSH
- imunita účinky léků MeSH
- imunizace * MeSH
- interleukin-6 analýza biosyntéza MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- oximy farmakologie MeSH
- protilátky analýza MeSH
- pyridinové sloučeniny farmakologie MeSH
- rovnováha Th1-Th2 účinky léků MeSH
- tvorba protilátek účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Caffeine is an alkaloid with a stimulant effect in the body. It can interfere in transmissions based on acetylcholine, epinephrine, norepinephrine, serotonin, dopamine and glutamate. Clinical studies indicate that it can be involved in the slowing of Alzheimer disease pathology and some other effects. The effects are not well understood. In the present work, we focused on the question whether caffeine can inhibit acetylcholinesterase (AChE) and/or, butyrylcholinesterase (BChE), the two enzymes participating in cholinergic neurotransmission. A standard Ellman test with human AChE and BChE was done for altering concentrations of caffeine. The test was supported by an in silico examination as well. Donepezil and tacrine were used as standards. In compliance with Dixon's plot, caffeine was proved to be a non-competitive inhibitor of AChE and BChE. However, inhibition of BChE was quite weak, as the inhibition constant, Ki, was 13.9 ± 7.4 mol/L. Inhibition of AChE was more relevant, as Ki was found to be 175 ± 9 µmol/L. The predicted free energy of binding was -6.7 kcal/mol. The proposed binding orientation of caffeine can interact with Trp86, and it can be stabilize by Tyr337 in comparison to the smaller Ala328 in the case of human BChE; thus, it can explain the lower binding affinity of caffeine for BChE with reference to AChE. The biological relevance of the findings is discussed.
- Publikační typ
- časopisecké články MeSH
Sulfur mustard (SM) is a vesicant chemical warfare agent that persists as a serious menace from the viewpoint of acute and chronic toxicity, simple synthesis and no effective treatment currently being available. The two most deleterious basic molecular mechanisms in SM poisoning are: inflammation and over-activation of poly(ADP-ribose) polymerase and the resulting DNA alkylation. Oxidative stress is the common consequence of these pathway activations. In the present review, the significance of oxidative stress in SM poisoning is discussed along with research on antioxidant therapy as a suitable antidote. The temporal dynamics of the redox imbalance, the antioxidant depletion and impact this has on tissues are described as the pathologies induced by SM. Special attention is paid to ameliorating the damage using low molecular weight antioxidants. Melatonin, epigallocatechin gallate and flavone derivatives, in particular, have been studied in recent experiments. The suitability of these antioxidants for therapy purposes is considered in a separate chapter. The review concludes with a view to the future and the studies needed on antioxidant therapy as a countermeasure to SM poisoning.
- MeSH
- antioxidancia chemie farmakologie terapeutické užití MeSH
- chemické bojové látky metabolismus otrava MeSH
- lidé MeSH
- oxidační stres účinky léků MeSH
- poly(ADP-ribosa)-polymerasy metabolismus MeSH
- poškození DNA účinky léků MeSH
- yperit metabolismus otrava MeSH
- zánět chemicky indukované farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Macrophages play an important role in the immune system. They also participate in multiple processes including angiogenesis and triggering of inflammation. The present study summarizes pieces of knowledge on the importance of macrophages in disease, especially the inflammation. Special attention is paid to the cholinergic anti-inflammatory pathway (CAP) associated with the nicotinic acetylcholine receptor (nAChR) and the parasympathetic nervous system. The current pharmacological effectiveness in suppressing the inflammation in general and the septic shock in particular, is limited. CAP was discovered recently and it seems to be a suitable target for the development of new drugs. Moreover, available drugs binding to either nAChR or acetylcholinesterase (AChE) are candidates for either an inhibition or enhancement of CAP. Though the current scientific databases do not include all necessary data on the association of CAP with body functions and the research is quite intensive, the objective of the present review is to introduce the current trends and to critically evaluate CAP and macrophage-associated pathways.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- antiflogistika nesteroidní chemie terapeutické užití MeSH
- cholinergní látky chemie terapeutické užití MeSH
- HIV infekce imunologie patologie MeSH
- hormony kůry nadledvin terapeutické užití MeSH
- lidé MeSH
- makrofágy imunologie MeSH
- nikotinové receptory metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- zánět farmakoterapie imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Assay of acetylcholinesterase (AChE) activity plays an important role in diagnostic, detection of pesticides and nerve agents, in vitro characterization of toxins and drugs including potential treatments for Alzheimer's disease. These experiments were done in order to determine whether indoxylacetate could be an adequate chromogenic reactant for AChE assay evaluation. Moreover, the results were compared to the standard Ellman's method. We calculated Michaelis constant Km (2.06 × 10(-4) mol/L for acetylthiocholine and 3.21 × 10(-3) mol/L for indoxylacetate) maximum reaction velocity V(max) (4.97 × 10(-7) kat for acetylcholine and 7.71 × 10(-8) kat for indoxylacetate) for electric eel AChE. In a second part, inhibition values were plotted for paraoxon, and reactivation efficacy was measured for some standard oxime reactivators: obidoxime, pralidoxime (2-PAM) and HI-6. Though indoxylacetate is split with lower turnover rate, this compound appears as a very attractive reactant since it does not show any chemical reactivity with oxime antidots and thiol used for the Ellman's method. Thus it can be advantageously used for accurate measurement of AChE activity. Suitability of assay for butyrylcholinesterase activity assessment is also discussed.
- Publikační typ
- časopisecké články MeSH
