Farmacja Polska (Mar 2021)
The role of oxidative stress in the etiology of selected civilization diseases
Abstract
The evolutionary ability to use oxygen in the process of respiration has provided living organisms with an efficient source of energy and made the development of life on Earth possible. However, oxygen and its derivatives can also pose a threat. During physiological processes, ROS (reactive oxygen species) are generated. Excessive amounts of these chemically active molecules may lead to the modification of biologically important macromolecules (proteins, nucleic acids), resulting in irreversible disturbances in the structure of key cell structures (cell nucleus, membranes). Another consequence of ROS activity is the disruption of signal transduction pathways in the cell, which leads to the development of many serious diseases (atherosclerosis, cancer). On the other hand, similarly to excess oxygen, its deficiency can be disastrous for cells. Hypoxia, i.e. a state of insufficient oxygen supply in relation to demand, is relevant not only in ischaemic heart disease and myocardial infarction but also in many other cardiovascular, neurodegenerative and even cancerous diseases. A major role in the response to hypoxia at the cellular level is played by hypoxia-inducible factor (HIF), whose hyperactivation is associated with multidirectional disruption of intracellular pathways. There is a close link between hypoxia-related phenomena and ROS at the molecular level, which is based on bidirectional regulation. Therefore, both factors should be considered together in regards to the development of many pathologies. Despite the role of ROS and hypoxia in the development of lifestyle diseases, which has been discussed for years, it has still not been possible to introduce effective targeted therapy in this area. Notwithstanding encouraging initial data, many studies have provided inconclusive results on the efficacy of antioxidant therapy in neurodegenerative, cardiovascular and cancer diseases. In the latter case, however, the use of hypoxia-activated drugs and HIF-1 inhibitors seems to be a promising strategy. This demonstrates the need for a better understanding of the mechanisms involved in the action of the aforementioned factors and warrants further research in this area. The aim of this work is to present the mechanism of action of RFTs and hypoxia, their role in the pathophysiology of the most common human diseases and their potential use as targets for therapy.
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