Biological importance of reactive oxygen species in relation to difficulties of treating pathologies involving oxidative stress by exogenous antioxidants

• Reactive oxygen species (ROS) are deleterious to essential biomacromolecules.
• Yet, starting from life origin and evolution, ROS are involved in various physiological processes.
• Many clinical trials failed to treat free-radical diseases by antioxidants likely due to affecting these critical processes.
• A concept of positive signaling role of ROS, formed as a result of tissue injury, is discussed.
• Undesired effects of ROS should be targeted exactly, at concrete sites of ROS production.

Findings about involvement of reactive oxygen species (ROS) not only in defense processes, but also in a number of pathologies, stimulated discussion about their role in etiopathogenesis of various diseases. Yet questions regarding the role of ROS in tissue injury, whether ROS may serve as a common cause of different disorders or whether their uncontrolled production is just a manifestation of the processes involved, remain unexplained. Dogmatically, increased ROS formation is considered to be responsible for development of the so-called free-radical diseases. The present review discusses importance of ROS in various biological processes, including origin of life, evolution, genome plasticity, maintaining homeostasis and organism protection. This may be a reason why no significant benefit was found when exogenous antioxidants were used to treat free-radical diseases, even though their causality was primarily attributed to ROS. Here, we postulate that ROS unlikely play a causal role in tissue damage, but may readily be involved in signaling processes and as such in mediating tissue healing rather than injuring. This concept is thus in a contradiction to traditional understanding of ROS as deleterious agents. Nonetheless, under conditions of failing autoregulation, ROS may attack integral cellular components, cause cell death and deteriorate the evolving injury.

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