**2. Reactive oxygen species**

In all animals and plants, maintaining a normal oxygen concentration is essential. In contrast, an imbalance in oxygen concentration will lead to consequences, such as hypoxia (low oxygen) and oxidative stress (high oxygen), which can lead to tissue damage and even cell death. Cigarettes, herbicides, nitrogen oxide, ozone, radiation, and some metals affect oxygen concentration and oxidative stress conditions [9].

ROS originates from the metabolic process of oxygen used to induce oxidative stress [10]. The sources of ROS production are divided into exogenous and endogenous. Vital molecule changes due to reaction with ROS can be associated with various chronic diseases, such as atherosclerosis, osteoarthritis, diabetes, Alzheimer's disease, degenerative neurological diseases, and cardiovascular disease (**Figure 1**) [11–16]. ROS concentration determines their role; so that in equilibrium, they can play a role as the second cellular messenger and regulator of biological processes, but an excessive increase of ROS concentration causes oxidative stress [17, 18].

In 1991, the relationship between the induction of oxidants (ionizing radiation) and the activation of transcription factors was identified [19]. ROS affects the redoxsensitive elements of some transcription factors, such as hypoxia-inducible factors (HIFs) and kinases like phosphatidylinositol 3-kinase (PI3K); thus, it is possible to regulate these factors by oxygen free radicals [1, 20]. It is not easy to use antioxidants, because the body needs a sufficient concentration of ROS for specific purposes, but antioxidants alter the redox biology and interfere with the body's normal functioning.
