Oxidative stress and free radicals related diseases of the newborn

Abstract

Free radicals (FRs) generation is an unavoidable consequence of the life in an oxygen-rich atmosphere. FRs can be considered a double-edged sword. Beneficial effects of FRs occur at moderate concentrations and involve physiological roles in cellular responses to noxia, as in defense against infectious agents, in the function of a number of cellular signaling pathways and the induction of a mitogenic response. The over-production of FRs and the insufficiency of an antioxidant mechanism result in oxidative stress (OS), a deleterious process and important mediator of damage to cell structures and tissues. It occurs at birth in all newborns as a consequence of the hyperoxic challenge after the transition from the hypoxic intrauterine environment to extrauterine life. During the perinatal period, OS can be magnified by others predisposing conditions such as hyperoxia, hypoxia, ischemia, hypoxia-reperfusion, inflammation and high levels of non-protein bound iron. Epidemiological studies linked OS occurring during fetal stages and early infancy with adverse health outcomes later in life, indicating that OS is an early event in the etiology of these chronic diseases. Newborns, especially if preterm, are particularly susceptible to OS and damage due to the increased generation of FRs, the lack of adequate antioxidant protection, and the inability to induce antioxidant defenses during the hyperoxic challenge at birth. This impairment of the oxidative balance has been thought to be the common factor of pathologies grouped together as “free radical disease in the neonate” that include retinopathy of prematurity (which may lead to blindness in severe cases), bronchopulmonary dysplasia (a particularly debilitating pulmonary lesion of the preterm infant), periventricular leukomalacia (an important cause of severe neurodisability) and necrotizing enterocolitis. In this review we discuss in detail these perinatal diseases. Particularly, we analyze the current knowledge about the role of OS in their pathogenesis.