Oxidative Stress

The term oxidative stress has been often used to indicate the outcome of oxidative damage to biologically relevant macromolecules such as: nucleic acids, proteins, lipids and carbohydrates. This occurs when oxidative stress-related molecules, produced in the extracellular environment or within the cell exceed cellular antioxidant defenses (Cadenas, 1989).
Molecular oxygen can easily accept unpaired electrons giving rise to a group of partially reduced species, generally termed ROS. The ROS include: superoxide (O2•−), H2O2, hydroxyl radical (HO.), peroxyl (ROO.) and alkoxyl (RO.) radicals, which may be implicated in the initiation and propagation of free radical chain reactions and are potentially highly deleterious to cells (Riley, 1994).
Hydrogen peroxide and O2•−, as well as HNE and related 4-hydroxy-2,3-alkenals (HAKs), the main aldehydic end products of lipid peroxidation, can act as potential mediators capable of affecting signal pathways as those mediated by NF-κB (Evans et al., 2002), and proliferative and functional response of target cells (Parola and Robino, 2001). Lipid peroxidation also generates reactive electrophilic compounds, mainly α, β-unsaturated aldehydes. These compounds react with DNA
HAKs inhibit DNA synthesis at high and cytotoxic doses. While, at very low and non cytotoxic doses, HAKs inhibit PDGF mitogenic signaling and proliferation of human HSCs, through specific inhibition of intrinsic tyrosine kinase activity associated with the PDGF-β receptor subunit. The inhibitory effect of HAKs is transient and HSCs regain the ability to proliferate as a response to PDGF within 48 h, such a recovery is associated with HAKs induced upregulation of PDGF-β receptors (Robino et al.,