Figure 3.

ROS sources and downstream cellular effects. Endogenous sources of ROS include mitochondrial metabolic reactions, NADPH oxidase activity, and microsomal cytochrome P450 detoxification pathways; exogenous sources comprehend ultraviolet radiation, X-rays and gamma-rays, ultrasounds, pesticides, herbicides, and xenobiotics. ROS are normal products of cell metabolism with physiological roles in the organisms. They regulate signalling pathways through changes in the activity of structural proteins, transcription factors, membrane receptors, ion channels, and protein kinases/phosphatases. However, when ROS levels rise, and antioxidant defence cannot neutralize them, the redox homeostasis is disrupted, and a new state referred to as oxidative stress (OS) arises. OS leads to impairment of redox signalling and induces damage to biomolecules. OS has a graded response with minor or moderated changes provoking an adaptive response and homeostasis restauration and violent perturbations leading to pathological insults, damage beyond repair, and even cell death. MR: membrane receptor; NOS: nitric oxide synthase; NOX: NADPH oxidase. Filled arrows indicate a direct action, while dashed arrows indicate indirect or simplified mechanisms.