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Oxidation-reduction changes and distribution of toxic and essential/trace elements in the rat brain induced by isoflurane and iron-dextran

Inhaled anesthetics are normally considered non-active, but under appropriate conditions, they are metabolized in reactive free radicals (ROS) and reacting with cellular parts, causing damage. In the brain, iron plays an important role in the production of myelin, metabolism of monoamine transmitters and GABA synthesis. On the other hand, the accumulation of iron in the brain changes brain cell metabolism and leads to increased oxidative stress and neurodegeneration. The aim of this study was to investigate the possible antioxidant/prooxidative effect of isoflurane and Fe-dextran, as well as their combined interaction on the rat brain tissue samples by: a) evaluation of the neuro-inflammation, measuring the relative weight of the brain compared to a healthy control group ; b) changes in the oxido-reduction status measuring the level of malondialdehyde (MDA, end product of lipid peroxidation) and glutathione (GSH), activity of catalase (CAT) and superoxide dismutase (SOD) ; c) NO analysis as well as distribution of essential and toxic metals by mass spectrometry inductively coupled plasma (ICP-MS). The results indicate that isoflurane causes oxidative stress in the brain, while its combination with Fe-dextran as well as Fe-dextran itself causes increased lipid peroxidation and neuro-inflammation. Because of the increased levels of oxidative stress and the formation of superoxide anions, the level of NO in the iron dextran treated group and its combination with isoflurane decreased due to the formation of peroxynitrite which as an intermediator for protein oxidation, lipid peroxidation, mitochondrial dysfunction causes apoptosis and necrosis respectively neurodegeneration. Furthermore, the results of ICP - MS indicate a statistically significant increase in toxic metals (Al, Pb) as well as essential elements in brain tissue (Fe, Zn) in the rats treated with iron dextran and combination of iron dextran and isoflurane compared to the control group. The biggest changes in the distribution of toxic and essential trace elements / elements are seen in the group treated with iron dextran and isoflurane compared to other groups. The results indicate that the iron dextran and the combination of iron dextran and isoflurane have a neurotoxic effect through increased lipid peroxidation, ROS, which ultimately leads to cell death and degeneration of brain tissue.

Oxidation-reduction changes, essential/trace elements , isoflurane, iron-dextran, neurodegeneration

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