Reactive Oxygen Species in Health and Disease (original) (raw)
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Reactive Oxygen Species: Its Effects on various Diseases
JOURNAL OF ADVANCES IN BIOTECHNOLOGY
A free radical is any molecule capable of independent existence that contains one or more free electrons. These free radicals fall under the broader category of reactive oxygen species (ROS). ROS such as O2- , H2O2, NO-, OH-, HOCl, ONOO- are toxic to cells. ROS act largely by driving several important molecular pathways that play important roles in pathologic processes including neurodegeneration. injury, atherosclerosis, and inflammatory responses and ischemia-reperfusion. ROS, as in various radicals ions leads to mitochondrial dysfunction and consequently other cell organelles damage either through environmental effect or through genetic or metabolic disorders. Reactive molecular species also disturbs other metabolic pathways in a manner that cell’s normal functionality gets disrupted. Though diseases caused by reactive oxygen species are many, this review has covered its effect on major diseases. The present review paper will provide the detail of mechanism of ROS and its effec...
Biochemical basis and metabolic interplay of redox regulation
Redox Biology, 2019
Accumulated evidence strongly indicates that oxidative stress, characterized by an imbalance between reactive oxygen species (ROS) production and antioxidants in favor of oxidants, plays an important role in disease pathogenesis. However, ROS can act as signaling molecules and fulfill essential physiological functions at basal levels. Each ROS would be different in the extent to stimulate and contribute to different pathophysiological effects. Importantly, multiple ROS generators can be activated either concomitantly or sequentially by relevant signaling molecules for redox biological functions. Here, we summarized the current knowledge related to chemical and biochemical features of primary ROS species and corresponding antioxidants. Metabolic pathways of five major ROS generators and five ROS clearance systems were described, including their ROS products, specific ROS enriched tissue, cell and organelle, and relevant functional implications. We provided an overview of ROS generation and induction at different levels of metabolism. We classified 11 ROS species into three types based on their reactivity and target selectivity and presented ROS homeostasis and functional implications in pathological and physiological status. This article intensively reviewed and refined biochemical basis, metabolic signaling and regulation, functional insights, and provided guidance for the identification of novel therapeutic targets.
A radical shift in perspective: mitochondria as regulators of reactive oxygen species
The Journal of experimental biology, 2017
Mitochondria are widely recognized as a source of reactive oxygen species (ROS) in animal cells, where it is assumed that over-production of ROS leads to an overwhelmed antioxidant system and oxidative stress. In this Commentary, we describe a more nuanced model of mitochondrial ROS metabolism, where integration of ROS production with consumption by the mitochondrial antioxidant pathways may lead to the regulation of ROS levels. Superoxide and hydrogen peroxide (H2O2) are the main ROS formed by mitochondria. However, superoxide, a free radical, is converted to the non-radical, membrane-permeant H2O2; consequently, ROS may readily cross cellular compartments. By combining measurements of production and consumption of H2O2, it can be shown that isolated mitochondria can intrinsically approach a steady-state concentration of H2O2 in the medium. The central hypothesis here is that mitochondria regulate the concentration of H2O2 to a value set by the balance between production and consum...
Antioxidants & Redox Signaling, 2014
Significance: Oxidative stress is a well established hallmark of cardiovascular disease and there is strong evidence for a causal role of reactive oxygen and nitrogen species (RONS) therein. Recent Advances: Improvement of cardiovascular complications by genetic deletion of RONS producing enzymes and overexpression of RONS degrading enzymes proved the involvement of these species in cardiovascular disease at a molecular level. Vice versa, overexpression of RONS producing enzymes as well as deletion of antioxidant enzymes was demonstrated to aggravate cardiovascular complications. Critical Issues: With the present overview we present and discuss different pathways how mitochondrial RONS interact (crosstalk) with other sources of oxidative stress, namely NADPH oxidases, xanthine oxidase and an uncoupled nitric oxide synthase. The potential mechanisms of how this crosstalk proceeds are discussed in detail. Several examples from the literature are summarized (including hypoxia, angiotensin II mediated vascular dysfunction, cellular starvation, nitrate tolerance, aging, hyperglycemia, b-amyloid stress and others) and the underlying mechanisms are put together to a more general concept of redox-based activation of different sources of RONS via enzyme-specific ''redox switches''. Mitochondria play a key role in this concept providing redox triggers for oxidative damage in the cardiovascular system but also act as amplifiers to increase the burden of oxidative stress. Future Directions: Based on these considerations, the characterization of the role of mitochondrial RONS formation in cardiac disease as well as inflammatory processes but also the role of mitochondria as potential therapeutic targets in these pathophysiological states should be addressed in more detail in the future. Antioxid. Redox Signal. 20, 308-324.
Mitochondrial metabolism of reactive oxygen species
Biochemistry (Moscow), 2005
Oxidative stress is considered a major contributor to etiology of both "normal" senescence and severe pathologies with serious public health implications. Mitochondria generate reactive oxygen species (ROS) that are thought to augment intracellular oxidative stress. Mitochondria possess at least nine known sites that are capable of generating superoxide anion, a progenitor ROS. Mitochondria also possess numerous ROS defense systems that are much less studied. Studies of the last three decades shed light on many important mechanistic details of mitochondrial ROS production, but the bigger picture remains obscure. This review summarizes the current knowledge about major components involved in mitochondrial ROS metabolism and factors that regulate ROS generation and removal. An integrative, systemic approach is applied to analysis of mitochondrial ROS metabolism, which is now dissected into mitochondrial ROS production, mitochondrial ROS removal, and mitochondrial ROS emission. It is suggested that mitochondria augment intracellular oxidative stress due primarily to failure of their ROS removal systems, whereas the role of mitochondrial ROS emission is yet to be determined and a net increase in mitochondrial ROS production in situ remains to be demonstrated.
Frontiers in Pharmacology, 2023
Increased production and buildup of reactive oxygen species (ROS) can lead to various health issues, including metabolic problems, cancers, and neurological conditions. Our bodies counteract ROS with biological antioxidants such as SOD, CAT, and GPx, which help prevent cellular damage. However, if there is an imbalance between ROS and these antioxidants, it can result in oxidative stress. This can cause genetic and epigenetic changes at the molecular level. This review delves into how ROS plays a role in disorders caused by oxidative stress. We also look at animal models used for researching ROS pathways. This study offers insights into the mechanism, pathology, epigenetic changes, and animal models to assist in drug development and disease understanding.
Roles of Reactive Oxygen Species in Diseases and Novel Antioxidant Therapeutics
MedPharmRes, 2017
Reactive oxygen species (ROS) or oxidative stress has been reported with strongly involving to pathogenesis of many diseases in human. On the other hand, ROS play a critical regulation as secondary signal to maintain intracellular redox equilibrium. Basically, the antioxidant defense systems in the body counteract with overproduced ROS. However, when the redox balance is broken under severe oxidative stress conditions, it leads to tissue injuries and numerous disorders. In this review, we briefl introduce the systems of ROS and antioxidants systems in the body and discuss the opposite roles of ROS in normal physiological conditions and diseases. For ROS-related diseases, conventional and currently developed antioxidant therapies are also described in this review.
Reactive oxygen species in disease: Rebuttal of a conventional concept
Journal of Controversies in Biomedical Research, 2015
The production of intracellular reactive oxygen species and reactive nitrogen species has long been proposed as leading to the random deleterious modification of macromolecules (i.e., nucleic acids, proteins) with an associated progressive development of the age associated systemic diseases (e.g., diabetes, Parkinson's disease) as well as contributing to the ageing process. Superoxide anion (hydrogen peroxide) and nitric oxide (peroxynitrite) comprise regulated intracellular second messenger pro-oxidant systems, with specific sub-cellular locales of production and are essential for the normal function of the metabolome and cellular electro-physiology. We have posited that the formation of superoxide anion and its metabolic product hydrogen peroxide, and nitric oxide, do not conditionally lead to random damage of macromolecular species such as nucleic acids or proteins. Under normal physiological conditions their production is intrinsically regulated that is very much consistent with their second messenger purpose of function. We further propose that the concept of an orally administered small molecule antioxidant as a therapy to abrogate free radical activity (to control oxidative stress) is a chimera. As such we consider that free radicals are not a major overwhelming player in the development of the chronic diseases or the ageing process.