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Journal ArticleDOI

Peroxynitrite: biochemistry, pathophysiology and development of therapeutics

TLDR
This Review focuses on pharmacological strategies to attenuate the toxic effects of peroxynitrite, which include its catalytic reduction to nitrite and its isomerization to nitrate by metalloporphyrins, which have led to potential candidates for drug development for cardiovascular, inflammatory and neurodegenerative diseases.
Abstract
Peroxynitrite--the product of the diffusion-controlled reaction of nitric oxide with superoxide radical--is a short-lived oxidant species that is a potent inducer of cell death Conditions in which the reaction products of peroxynitrite have been detected and in which pharmacological inhibition of its formation or its decomposition have been shown to be of benefit include vascular diseases, ischaemia-reperfusion injury, circulatory shock, inflammation, pain and neurodegeneration In this Review, we first discuss the biochemistry and pathophysiology of peroxynitrite and then focus on pharmacological strategies to attenuate the toxic effects of peroxynitrite These include its catalytic reduction to nitrite and its isomerization to nitrate by metalloporphyrins, which have led to potential candidates for drug development for cardiovascular, inflammatory and neurodegenerative diseases

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How mitochondria produce reactive oxygen species.

TL;DR: The description outlined here facilitates the understanding of factors that favour mitochondrial ROS production and develops better methods to measure mitochondrial O2•− and H2O2 formation in vivo, as uncertainty about these values hampers studies on the role of mitochondrial ROS in pathological oxidative damage and redox signalling.
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Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal.

TL;DR: This review focuses on biochemical concepts of lipidPeroxidation, production, metabolism, and signaling mechanisms of two main omega-6 fatty acids lipid peroxidation products: malondialdehyde (MDA) and, in particular, 4-hydroxy-2-nonenal (4-HNE), summarizing not only its physiological and protective function as signaling molecule stimulating gene expression and cell survival, but also its cytotoxic role inhibiting geneexpression and promoting cell death.
Journal ArticleDOI

Reconciling the chemistry and biology of reactive oxygen species

TL;DR: This review examines how target selectivity and antioxidant effectiveness vary for different oxidants and highlights areas where greater understanding is required on the fate of oxidants generated by cellular NADPH oxidases and on the identification of oxidant sensors in cell signaling.
Journal ArticleDOI

Redox Regulation of Cell Survival

TL;DR: The current understanding of how disturbance in redox homeostasis may affect cell death and contribute to the development of diseases such as cancer and degenerative disorders is reviewed and the basic knowledge on redox regulation of cell survival can be used to develop strategies for the treatment or prevention of those diseases.
References
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Journal ArticleDOI

Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide.

TL;DR: It is proposed that superoxide dismutase may protect vascular tissue stimulated to produce superoxide and NO under pathological conditions by preventing the formation of peroxynitrite.
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Nitric Oxide and Peroxynitrite in Health and Disease

TL;DR: Current evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion, which is presented in detail in this review.
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Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of superoxide and nitric oxide.

TL;DR: Peroxynitrite anion was a less effective thiol-oxidizing agent than its anion, with oxidation presumably mediated by the decomposition products, hydroxyl radical and nitrogen dioxide.
Journal ArticleDOI

Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor

TL;DR: It is demonstrated that EDRF is protected from breakdown by superoxide dismutase (SOD) and Cu2+, but not by catalase, and is inactivated by Fe2+.
Journal ArticleDOI

Peroxynitrite-induced membrane lipid peroxidation : the cytotoxic potential of superoxide and nitric oxide

TL;DR: It is concluded that the conjugate acid of peroxynitrite, peroxlynitrous acid (ONOOH), and/or its decomposition products, i.e., .OH and nitrogen dioxide (.NO2), initiate lipid peroxidation without the requirement of iron.
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