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Nitric oxide is produced by almost all cardiac cells, endothelial cells, cardiomyocytes and nerve fibers. It is synthesized by an enzyme, a nitric oxide synthase, which occurs in endothelial, neural and inducible form. The distribution of nitric oxide synthase in the heart is characterized by a pronounced non-uniformity. Nitric oxide exerts its effects in physiological and pathophysiological conditions. The physiological effects of low concentrations of nitric oxide, which is released in the normal conditions under the influence of constituent enzymes, occur via cyclic guanosine monophosphate. The synthesized nitric oxide exhibits its effect in the cells where it is produced, in an autocrine manner, or by diffusing into the neighboring cells, in a paracrine manner. Nitric oxide acts by regulating the coronary vessel tonus, affecting the contractility of cardiomyocytes, generating an inotropic effect in a dose-dependent manner and controlling the cellular respiration. Other effects of nitric oxide in the cardiovascular system include the hyperpolarization of the smooth muscle cells in blood vessels, the inhibition of the monocyte adhesion, the inhibition of platelet migration, adhesion and aggregation and the proliferation of smooth muscle cells and fibroblasts. The anti-atherosclerotic effects of nitric oxide are based on these effects. Nitric oxide is a weak free radical in gaseous state, and the cytotoxic and/or the cytoprotective effects of the higher concentrations of nitric oxide are related to the chemical structure of nitric oxide as a free radical. The excessive production of nitric oxide by the activation of inducible nitric oxide synthase can lead to major irregularities in the function of cardiomyocytes and cardiac insufficiency. Understanding the nitric oxide molecular mechanisms of signaling pathways in the heart can provide a new strategic approach to prevention and treatment of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Introduction Reactive oxygen species are particularly active in the brain and neuronal tissue, and they are involved in numerous cellular functions, including cell death and survival. Brain and oxidative stress A high metabolic rate and an abundant supply of the transition metals make the brain an ideal target for a free radical attack. In addition, the brain has a high susceptibility to oxidative stress due to the high lipid content and relatively lower regenerative capacity in comparison with other tissues. Vulnerability of nerve cells to oxidative stress The neurons are more vulnerable to oxidative stress than other brain cell types. In addition to the two conventional enzymes, catalase and glutathione peroxidase, peroxiredoxins remove intracellular hydrogen peroxide by reducing it to water. The recent work increasingly supports the hypothesis that peroxiredoxins are not only antioxidant proteins, but they also play a role in cell signaling by controlling hydrogen peroxide and alkyl hydroperoxide levels. The accumulating evidence demonstrates that microglia can become deleterious and damage neurons. The overactivated microglia release reactive oxygen species that cause neuronal damage in neurodegenerative diseases. Conclusion The defense of nerve cells against reactive oxygen species - mediated oxidative damage is essential for maintaining the functionality of nerve cells. The ongoing studies show that neuron-glial compartmentalization of antioxidants is critical for the neuronal signaling by hydrogen peroxide as well as the neuronal protection. [ABSTRACT FROM AUTHOR]

Introduction Oxidative stress and oxygen free radicals are thought to play an important role in acute effects of a number of neurotoxic processes. 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy), a ring substituted amphetamine derivate, has attracted a great deal of media attention in recent years due to its widespread abuse as recreational drug by the young generation. The aim of the present study was to evaluate the acute effects of 3,4-methylenedioxymethamphetamine on oxidative stress parameters (index of lipid peroxidation - ILP, superoxide radicals O2-, superoxide dismutase - SOD and glutathione - GSH) in frontal cortex, striatum and hippocampus in Wistar rats. Materials and methods The study included 40 male Wistar rats (200-250 g), housed 4 per cage having Fee access to food and water. MDMA was dissolved in distillated water and administered peroraly at 5, 10, 20 or 40 mg/kg. 8 hours following MDMA, the rats were killed by decapitation, their brains were rapidly removed and the brain structures were dissected out on ice and analyzed biochemically. Results Acute peroral administration of a single dose (5, 10, 20 and 40 mg/kg) resulted in increase of ILP, O2-, SOD and decrease of GSH. Conclusion The results obtained in the present study suggest that oxidative stress plays a crucial role in MDMA-induced neurotoxicity and that the mechanism of MDMA neurotoxycity may vary between brain regions. [ABSTRACT FROM AUTHOR]