Anticancer drugs as a potential source of OS are listed in Table 2. Sarco/Endoplasmic ReticulumMitochondria Complex and Calcium OverloadEnergy Failure Sarco/Endoplasmic ReticulumMitochondria Complex Mitochondria play a central role in the life and death of cells. cause fast depletion of antioxidant Tnf protection including the homocystein-methionine system, whose activity decreases with age. The alteration of effector subcellular structures (mitochondria, sarco/endoplasmic reticulum) and subsequent changes in cellular energetics and calcium turnover may also occur and lead to the disruption of cellular function, including neurons and cardiomyocytes. On the organ level (nervous system and heart), neurocardiogenic stunning may occur. The effects of OS correspond to the effect of high doses of catecholamines in the experiment. Intensive OS might represent for this acute clinical condition. TTS might be significantly more complex A 286982 pathology than currently perceived so far. – Catecholamines (exogenous source)- Toxins, chemicals, drugs (incl. tobacco, caffeine, cocaine), allergens, vaccines, blood transfusion- Photochemical smog (incl. UV A 286982 radiation, pollution from transport and industry)Endogenous sources- Physical stress- Emotional stress- Catecholamines (endogenous source)- Emergency and acute clinical conditions (incl. infections)- Fenton reaction (i.e., all conditions associated with bleeding including injuries, operations, invasive procedures)- Epileptic seizures- Immunopathological conditions and diseases (incl. acute allergic reactions and delayed-type hypersensitivity)- Acute and chronic inflammations- Chronic disorders (e.g., autoimmune, degenerative, demyelinating, metabolic)- Malignancies Open in a separate window Due to the biochemical pathways, OS is usually associated with various pathologies or comorbidities potentially leading to TTS. OS sources that can be combined with each other are discussed in detail. Oxidative Stress Oxidative Stress in Medicine Oxidative stress as a concept in redox biology and medicine represents an imbalance between oxidants and antioxidants in favor of the oxidants, leading to a disruption of redox signaling and control and/or molecular damage (22, 23, 25C27). As the ballast of metabolic processes, OS denotes deviation from redox constant state and evokes stress responses (25). Under aerobic conditions, more than 90% of the oxygen consumed is usually reduced directly to water by cytochrome oxidase in the electron transport chain (ETC) using a four-electron mechanism (28C30). ETC located in eukaryotic cells around the inner mitochondrial membrane is usually A 286982 associated with oxidative phosphorylation and energy production in the form of ATP from various substrates. Less than 10% of the consumed oxygen is usually reduced by one-electron conversion to the superoxide radical (O2-); by the reduction by another electron and the A 286982 addition of two protons, hydrogen peroxide (H2O2) is usually formed (29C31). Reactive species (RS) associated with OS can adversely affect biologically important molecules C lipids, proteins and nucleic acids. OS is usually involved in the A 286982 development of a number of pathologies such as hypertension, dyslipidemia, metabolic diseases, incl. diabetes mellitus, neurodegenerative disorders, respiratory and inflammatory diseases or malignancies. They also represent TTS comorbidities (7, 13, 24, 32, 33). In healthy adult women aged 19C78 years, significantly higher levels of lipid peroxidation were found by evaluating the levels of malondialdehyde and F2-isoprostanes. Plasma levels of C-reactive protein (CRP) and cholesterol also positively correlated with both biomarkers (34). Autoantibodies to oxidized DNA were 50 percent higher in women than in men (35). In contrast, ascorbic acid in plasma showed a strong inverse relationship with lipid peroxidation (34). Similarly low concentrations of total glutathione (the most important endogenous antioxidant) were found in the blood of healthy individuals of various ages, primarily those aged between 60 and 79 C see also paragraph 7 (36). These facts suggest a relationship between OS, gender and age, which is important for TTS. Oxidative Stress and Reactive Species RS arise in the body from exogenous and endogenous sources (22C24). They.