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Brno, Czech Republic

Pohanka M.,University of Hradec Kralove | Pohanka M.,Karel Englis College, Brno
Interdisciplinary Toxicology | Year: 2014

Cholinesterases are enzymes able to hydrolyze the neurotransmitter acetylcholine and thus to terminate transmission. Once the enzymes are inhibited, excitotoxicity can appear in the adjacent cells. It is well known that oxidative stress is involved in the toxicity of cholinesterase inhibitors. Commonly, stress follows inhibition of cholinesterases and disappears shortly afterwards. In the present experiment, it was decided to test the impact of an inhibitor, neostigmine, on oxidative stress in BALB/c mice after a longer interval. The animals were sacrificed three days after onset of the experiment and spleens and livers were collected. Reduced glutathione (GSH), glutathione reductase (GR), glutathione S-transferase (GST), thiobarbituric acid reactive substances (TBARS), ferric reducing antioxidant power (FRAP), caspase-3 and activity of acetylcholinesterase (AChE) were assayed. The tested markers were not altered with exceptions of FRAP. The FRAP values indicate accumulation of low molecular weight antioxidants in the examined organs. The role of low molecular weight antioxidants in the toxicity of AChE inhibitors is discussed. © 2015 Interdisciplinary Toxicology. Source

Pohanka M.,University of Hradec Kralove | Pohanka M.,Karel Englis College, Brno
Chemical Papers | Year: 2015

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are enzymes expressed in the human body under physiological conditions. AChE is an important part of the cholinergic nerves where it hydrolyses neurotransmitter acetylcholine. Both cholinesterases are sensitive to inhibitors acting as neurotoxic compounds. In analytical applications, the enzymes can serve as a biorecognition element in biosensors as well as simple disposable sensors (dipsticks) and be used for assaying the neurotoxic compounds. In the present review, the mechanism of AChE and BChE inhibition by disparate compounds is explained and methods for assaying the enzymes activity are shown. Optical, electrochemical, and piezoelectric biosensors are described. Attention is also given to the application of sol-gel techniques and quantum dots in the biosensors' construction. Examples of the biosensors are provided and the pros and cons are discussed. © 2015 Institute of Chemistry, Slovak Academy of Sciences 2015. Source

Pohanka M.,University of Hradec Kralove | Pohanka M.,Karel Englis College, Brno
Journal of Applied Biomedicine | Year: 2015

Caffeine is a secondary plant metabolite found in coffee and tea. Its major pathway is interaction with adenosine receptors. Minor pathways are also known. An effect of caffeine on immunity has been proposed. In this paper, the role of caffeine on the immune system was studied, using a BALB/c mouse model. The animals received saline (controls), keyhole limpet hemocyanin (KLH) 1 mg/kg or caffeine (alone or in combination with KLH) in doses of 1-16 mg/kg. The mice were sacrificed 1-7 days later and plasma levels of interleukin (IL) 2, 4, 6, 10, 12 and antibodies against KLH were determined by enzyme linked immunosorbent assay (ELISA). Caffeine caused a significant decrease in KLH-stimulated antibody produc-tion. The effect was dose dependent. There were similar findings for IL-2 and IL-4 but not for IL-6, IL-10 and IL-12. The significance of the findings is discussed with extrapolation to humans based on caffeine doses used in the study and the amount of caffeine in available beverages. © 2014 Faculty of Health and Social Studies, University of South Bohemia in Ceske Budejovice. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved. Source

Pohanka M.,University of Hradec Kralove | Pohanka M.,Karel Englis College, Brno
Current Medicinal Chemistry | Year: 2014

Alzheimer's disease (AD) is a neurodegenerative disorder with no known cure and rapid rise in incidence. The predominant cognitive impairment is currently treated using cognitive enhancers like cholinesterase inhibitors. The two molecular hallmarks of AD are amyloid plaques created from an amyloid precursor protein and hyperphosphorylated tau protein that is deposited as neurofibrillary tangles inside neurons. A number of pathological mechanisms follow or precede these formations. Alteration in mitochondrial function and deposition of heavy metals are reported. The disease progression is enhanced by oxidative stress. However, the role of oxidative stress is not universally accepted. The current review covers and discusses the basic evidence and role of oxidative stress in AD development. © 2014 Bentham Science Publishers. Source

Pohanka M.,University of Hradec Kralove | Pohanka M.,Karel Englis College, Brno
International Journal of Molecular Sciences | Year: 2014

Acetylcholinesterase (AChE) inhibitors are widely used for the symptomatic treatment of Alzheimer's disease and other dementias. More recent use is for myasthenia gravis. Many of these inhibitors interact with the second known cholinesterase, butyrylcholinesterase (BChE). Further, evidence shows that acetylcholine plays a role in suppression of cytokine release through a "cholinergic anti-inflammatory pathway" which raises questions about the role of these inhibitors in the immune system. This review covers research and discussion of the role of the inhibitors in modulating the immune response using as examples the commonly available drugs, donepezil, galantamine, huperzine, neostigmine and pyridostigmine. Major attention is given to the cholinergic anti-inflammatory pathway, a well-described link between the central nervous system and terminal effector cells in the immune system. © 2014 by the authors; licensee MDPI, Basel, Switzerland. Source

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