Oxygen Toxicity and Reactive Oxygen Species: The Devil Is in the Details

Abstract

ABSTRACT:Reactive oxygen species (ROS) serve as cell signaling molecules for normal biologic processes. However, the generation of ROS can also provoke damage to multiple cellular organelles and processes, which can ultimately disrupt normal physiology. An imbalance between the production of ROS and the antioxidant defenses that protect cells has been implicated in the pathogenesis of a variety of diseases, such as cancer, asthma, pulmonary hypertension, and retinopathy. The nature of the injury will ultimately depend on specific molecular interactions, cellular locations, and timing of the insult. This review will outline the origins of endogenous and exogenously generated ROS. The molecular, cellular, pathologic, and physiologic targets will then be discussed with a particular emphasis on aspects relevant to child development. Finally, antioxidant defenses that scavenge ROS and mitigate associated toxicities will be presented, with a discussion of potential therapeutic approaches for the prevention and/or treatment of human diseases using enzymatic and nonenzymatic antioxidants. . This review will focus on-1) origins of ROS: environment, cells, and cellular components; 2) molecular targets: classic and novel macromolecular targets and associated toxicity in infants and children; 3) antioxidant defenses: developmental regulation and vulnerabilities; and 4) antioxidant therapies: enzymatic and nonenzymatic approaches. Origins of ROSOxygen has a unique molecular structure and is abundant within cells. It readily accepts free electrons generated by normal oxidative metabolism within the cell, producing ROS, such as O 2 ·Ϫ and hydroxyl radical (HO · ), as well as the oxidant H 2 O 2 . Processes causing uncoupling of electron transport can enhance the production of ROS, with mitochondria being a major source (4). However, other cellular components, such as endoplasmic reticulum-bound enzymes, cytoplasmic enzyme systems, and the surface of the plasma membrane, also contribute (5,6). Activity of multiple enzyme systems, such as the cytochrome P 450 monoxygenase system, xanthine oxidoreductase, nitric oxide synthases, and several others involved in the inflammatory process (cyclooxygenase and lipoxygenase), can also increase the generation of ROS.

Differential effects of docosahexaenoic acid on preterm and term placental pro-oxidant/antioxidant balance

“…Oxidative damage is elevated in conditions that complicate pregnancy and result in preterm birth (Myatt 2010), with excessive ROS production playing a significant role in the development of oxygen radical diseases of the newborn (Auten & Davis 2009). Recent clinical studies of maternal dietary supplementation with fish oil or other DHA-containing supplements suggest that some clinical benefits exist, such as a reduction in preterm birth rates; however, this compound is well known to exert pro-oxidant effects.…”

Effects of astaxanthin on oxidative stress induced by Cu2+ in prostate cells

“…Low intracellular Cu 2+ concentrations could influence the activities of these enzymes and the normal metabolisms of the cells. Interestingly, the redox properties of the metal also mediate its toxicity because uncontrolled production of reactive oxygen species (ROS) results in oxidative stress, which does not follow a correct antioxidant response and consequently damages the biological macromolecules such as nucleic acids, proteins, and lipids (Adler et al, 1999;Auten and Davis, 2009;Maltepe and Saugstad, 2009;Linder, 2012 intake, distribution, utilization, and excretion are precisely regulated (Rosenzweig and O'Halloran, 2000;Kim et al, 2008;de Feo et al, 2009;Banci et al, 2010;Festa and Thiele, 2011;Haas et al, 2011).…”

Obesity, reproduction and oxidative stress

“…Когда количество свободных радикалов превышает активность антиоксидантной защиты, формируется состояние, называемое оксида-тивным стрессом [41]. Патологическое действие сво-бодных радикалов заключается в повреждении ДНК, перекисном окислении липидов и белков [42].…”