**3. ROS in physiological conditions**

Reactive oxygen species are continuously produced in the cells, especially during mitochon‐ drial electron transport chain and eliminated in biological systems, where in physiological conditions (low levels), they play crucial roles in the regulation of different cell's functions, including cell proliferation, apoptosis, transformation, and senescence [7].

The mechanism of action of ROS in activation of cell proliferation or different signal pathways implies the interaction between ROS and cysteine residues leading to the formation of disulfide bonds and activation of signal transducing pathways. The activation of these processes may occur via kinase activation or phosphatase inhibition, and via regulation of proteinases, including matrix metalloproteinases (see Figure 1) [14].

Besides their toxic effects, it was demonstrated that reactive oxygen species interfere in main cellular processes (differentiation, organogenesis, wound healing, cell fate regula‐ tion), in the activity of different enzymes (kinases and phosphatase), transcription factors, ionic channels and transporters [6]. Moreover, it appears that ROS acts as an essential cellular messenger alongside with the acknowledged second messengers (Ca2+, arachidon‐ ic acid, cAMP and IP3) [6].

Pan and coworkers stated that ROS are involved in the microbicidal activity of phagocytes, regulation of signal transduction and gene expression, and act as inducers of oxidative damage to macromolecules (nucleic acids, proteins, and lipids) (see Figure 1) [29].

**Figure 1.** ROS cellular functions in physiological conditions (the picture was obtained by using Servier Medical Art templates).

Most of the free radicals generated by various cellular metabolic systems originate from oxygen. The percent of molecular oxygen that is converted into superoxide and hydroxyl radicals at mitochondrial level is 5%. Mounting evidence indicates that the free radicals resulted have major function in the normal metabolism of cells: they are used in the synthesis of prostaglandins, cholesterol and steroidal hormones. Furthermore, the biosynthesis of collagen demands the participation of hydroxyl free radicals [16].

The effects and functions of ROS are distinct and dependent of their concentration, for example: low concentrations of mitochondrial ROS are associated with metabolic adapta‐ tion in hypoxic conditions; moderate concentrations are involved in the regulation of inflammatory response and high levels stimulate apoptosis/autophagy pathways responsi‐ ble of inducing cell death [11].

Other beneficial effects of ROS refer to their involvement in the intracellular killing of bacte‐ ria by neutrophil granulocytes, detoxification of the liver and certain cell signaling processes [20, 30].

There is also considerable information regarding the roles of mitochondrial ROS (superoxide anion and hydrogen peroxide) in inflammatory cytokine production and innate immune responses by activation of newly characterized RIG-I-like receptors (RLRs), inflammasomes, and mitogen activated protein kinases (MAPK) [11, 31, 32].
