Oxidative stress

Abstract

Considerable evidence implicates oxidative stress in the pathophysiology of many complications of human pregnancy, and this topic has now become a major focus of both clinical and basic science research. Oxidative stress arises when the production of reactive oxygen species overwhelms the intrinsic anti-oxidant defences. Reactive oxygen species play important roles as second messengers in many intracellular signalling cascades aimed at maintaining the cell in homeostasis with its immediate environment. At higher levels, they can cause indiscriminate damage to biological molecules, leading to loss of function and even cell death. In this chapter, we will review how reactive oxygen species are generated and detoxified in the human placenta, and what roles they may play at homeostatic concentrations. We will then consider their involvement in normal placental development, and in complications ranging from miscarriage to pre-eclampsia and premature rupture of the membranes.

Cannabinoids, the Heart of the Matter

“…Oxidative stress arises when the production of reactive oxygen species exceeds the total antioxidant capacity of the body. Reactive oxygen species act as second messengers in signaling cascades in the cardiovascular system and are produced by cardiac mitochondria 22, 23. When the concentration of reactive oxygen species exceeds total antioxidant capacity, damage can be caused to biomolecules, eventually leading to loss‐of‐function and cell death.…”

Oxidative stress in pregnancy and fertility pathologies

“…Oxidative stress is the term used to designate an imbalance between reactive oxygen species (ROS) and anti-oxidant levels in a cell, favoring the former (Burton and Jauniaux 2011;Dalle-Donne et al 2006;Dröge 2002;Halliwell 2003). ROS include free-radical intermediates such as superoxide anion radical (O 2 · − ; the most abundant under physiological conditions (Burton and Jauniaux 2011)), hydroxyl radical (HO·), peroxyl radical (ROO·), alkoxyl radical (RO·), and hydroperoxyl radical (HO· 2 ), and non-radical intermediates such as hydrogen peroxide (H 2 O 2 ), ozone (O 3 ), hypochlorous acid (HOCl), peroxynitrite (ONOO-), and singlet oxy-gen ( 1 O 2 ).…”

“…ROS include free-radical intermediates such as superoxide anion radical (O 2 · − ; the most abundant under physiological conditions (Burton and Jauniaux 2011)), hydroxyl radical (HO·), peroxyl radical (ROO·), alkoxyl radical (RO·), and hydroperoxyl radical (HO· 2 ), and non-radical intermediates such as hydrogen peroxide (H 2 O 2 ), ozone (O 3 ), hypochlorous acid (HOCl), peroxynitrite (ONOO-), and singlet oxy-gen ( 1 O 2 ). These compounds have high instability due to the existence of one or more, unpaired electrons (Aherne and O'Brien 2000;Dalle-Donne et al 2003;Valko et al 2007).…”

“…O 2 reduction to water implies a 1-2 % electron leakage, generating O 2 · − at the ubiquinone and NADH dehydrogenase (complex I) level, as well as in complex III; & Radiation, exciting UV rays, and ionizing X rays; & Xenobiotics and drug metabolism; & The activity of monoamine oxidase, which deaminates biogenic amines. This mechanism occurs at the outer membrane of the mitochondria and is associated to large H 2 O 2 production; & In purine catabolism and formation of uric acid, in the reactions catalyzed by xanthine oxidase, a O 2 · − -producing enzyme (Myatt and Cui 2004); & In the reactions catalyzed by xanthine oxidoreductase, nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase, nitric oxide synthase, and heme oxygenase, and in the formation o f peroxynitrite (Myatt and Cui 2004); & during an inflammatory response, the production of H 2 O 2 and O 2 · − greatl y increases in cells such as polymorphonuclear cells, eosinophils, monocytes, Kupffer cells, and macrophages, thanks to a highly specialized NAD(P)H-dependent oxidase system located in the outer surface of the cell membrane, coupled to the action of superoxide dismutase (SOD) (Burton and Jauniaux 2011;Poli et al 2004); & during protein folding taking place in the endoplasmic reticulum, where a significant amount of O 2 · − is formed. In this process, the formation of disulfide bonds is an oxidative process, since it involves the oxidation of sulfhydryl groups of cysteine residues (Burton and Jauniaux 2011;Burton et al 2009;Poli et al 2004).…”

“…At homeostatic levels, ROS are implicated in diverse actions on cell function, including activation of redoxsensitive transcription factors and activation of protein kinases (Burton and Jauniaux 2011), regulation of vascular tone and functions controlled by O 2 c o n c e n t r a t i o n s , enhancement of signal transduction from many membrane receptors (e.g., the antigen receptor of lymphocytes) (Dröge 2002), combating pathogens (Myatt and Cui 2004), among others. However, when in excess, ROS can induce cell injury and a chronic inflammatory state that can trigger a cascade of free-radical reactions, promoting secondary ROS generation and resulting in cellular modification and damage in DNA, carbohydrates, proteins, and polyunsaturated fatty acids.…”