Since excessive amounts of catecholamines are known to produce arrhythmias and increase the plasma level of aminochrome, an oxidation product of catecholamines, we tested the hypothesis that antioxidants may reduce the formation of aminochrome and prevent the catecholamine-induced arrhythmias. For this purpose, Sprague-Dawley rats were pretreated orally, with vitamin A or vitamin C for 21 days, and their effects on ventricular arrhythmias induced by a bolus dose or cumulative doses of intravenous epinephrine were examined. Electrocardiogram recording of these animals revealed that pretreatment with either of these vitamins increased the time of onset and decreased the duration of the epinephrine-induced ventricular arrhythmias. Ventricular fibrillations due to high doses of epinephrine were also prevented by the antioxidant pretreatment. Although pretreatment with either vitamin A or vitamin C did not affect the basal malondialdehyde level in control animals, the increase in malondialdehyde level caused by epinephrine administration was significantly reduced by these agents. The elevated level of plasma aminochrome due to epinephrine was also decreased by vitamins A and C treatments. The results indicate that antioxidant may prevent catecholamine-induced arrhythmias by reducing the formation of aminochrome and thus may provide a new strategy for the management of stress-related heart disease.
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http://dx.doi.org/10.1007/s12012-009-9051-5 | DOI Listing |
Antioxidants (Basel)
September 2024
Molecular & Clinical Pharmacology, Instituto de Ciencias Biomédicas (ICBM), Faculty of Medicine, University of Chile, Santiago 8380453, Chile.
Recently, a single-neuron degeneration model has been proposed to understand the development of idiopathic Parkinson's disease based on (i) the extremely slow development of the degenerative process before the onset of motor symptoms and during the progression of the disease and (ii) the fact that it is triggered by an endogenous neurotoxin that does not have an expansive character, limiting its neurotoxic effect to single neuromelanin-containing dopaminergic neurons. It has been proposed that aminochrome is the endogenous neurotoxin that triggers the neurodegenerative process in idiopathic Parkinson's disease by triggering mitochondrial dysfunction, oxidative stress, neuroinflammation, dysfunction of both lysosomal and proteasomal protein degradation, endoplasmic reticulum stress and formation of neurotoxic alpha-synuclein oligomers. Aminochrome is an endogenous neurotoxin that is rapidly reduced by flavoenzymes and/or forms adducts with proteins, which implies that it is impossible for it to have a propagative neurotoxic effect on neighboring neurons.
View Article and Find Full Text PDFMikrochim Acta
July 2024
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China.
Copper selenide nanoparticles (CuSeNP) were synthesized using histidine, ethylenediamine, and sodium selenate as precursors by one-step microwave digestion methods. The as-prepared CuSeNPs exhibit excellent catechol oxidase mimic enzyme and catalase (CAT)-like activities. Dopamine (DA) can be oxidized to aminochrome with HO by CuSeNPs, and the intermediate product aminochrome can further react with α-naphthol to yield a highly fluorescent derivative.
View Article and Find Full Text PDFBiomolecules
June 2024
Molecular & Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Santiago 8330111, Chile.
One of the biggest problems in the treatment of idiopathic Parkinson's disease is the lack of new drugs that slow its progression. L-Dopa remains the star drug in the treatment of this disease, although it induces severe side effects. The failure of clinical studies with new drugs depends on the use of preclinical models based on neurotoxins that do not represent what happens in the disease since they induce rapid and expansive neurodegeneration.
View Article and Find Full Text PDFInt J Biochem Cell Biol
March 2024
Department of Pharmacology and Physiology, Oklahoma State University College of Osteopathic Medicine, Tahlequah, OK, USA.
Parkinson's disease (PD) is a neurodegenerative disorder that progresses over time and is characterized by preferential reduction of dopaminergic neurons in the substantia nigra. Although the precise mechanisms leading to cell death in neurodegenerative disorders, such as PD, are not fully understood, it is widely accepted that increased oxidative stress may be a prevalent factor contributing to the deterioration of the nigrostriatal dopaminergic fibers in such conditions. Aminochrome, generated from dopamine (DA) metabolism, plays an important role in multiple pathogenic mechanisms associated with PD.
View Article and Find Full Text PDFAntioxidants (Basel)
March 2023
Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, SE-10691 Stockholm, Sweden.
Investigations of the effect of antioxidants on idiopathic Parkinson's disease have been unsuccessful because the preclinical models used to propose these clinical studies do not accurately represent the neurodegenerative process of the disease. Treatment with certain exogenous neurotoxins induces massive and extremely rapid degeneration; for example, MPTP causes severe Parkinsonism in just three days, while the degenerative process of idiopathic Parkinson´s disease proceeds over many years. The endogenous neurotoxin aminochrome seems to be a good alternative target since it is formed in the nigrostriatal system neurons where the degenerative process occurs.
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