Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury.

By S. Cuzzocrea, D. Riley, A. Caputi, D. Salvemini. Pharmacological Reviews, 2001

1,159 citations recorded by the source corpus.

A vast amount of circumstantial evidence implicates oxygen-derived free radicals (especially superoxide and hydroxyl radical) and high-energy oxidants (such as peroxynitrite) as mediators of inflammation, shock, and ischemia/reperfusion injury. The aim of this review is to describe recent developments in the field of oxidative stress research. The first part of the review focuses on the roles of reactive oxygen species (ROS) in shock, inflammation, and ischemia/reperfusion injury. The second part of the review deals with the novel findings using recently identified pharmacological tools (e.g., peroxynitrite decomposition catalysts and selective superoxide dismutase mimetics (SODm) in shock, ischemia/reperfusion, and inflammation. 1) The role of ROS consists of immunohistochemical and biochemical evidence that demonstrates the production of ROS in shock, inflammation, and ischemia/reperfusion injury. ROS can initiate a wide range of toxic oxidative reactions. These include initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3-phosphate dehydrogenase, inhibition of membrane sodium/potassium ATPase activity, inactivation of membrane sodium channels, and other oxidative modifications of proteins. All these toxicities are likely to play a role in the pathophysiology of shock, inflammation, and ischemia/reperfusion. 2) Treatment with either peroxynitrite decomposition catalysts, which selectively inhibit peroxynitrite, or with SODm, which selectively mimic the catalytic activity of the human superoxide dismutase enzymes, have been shown to prevent in vivo the delayed vascular decompensation and the cellular energetic failure associated with shock, inflammation, and ischemia/reperfusion injury. ROS (e.g., superoxide, peroxynitrite, hydroxyl radical, and hydrogen peroxide) are all potential reactants capable of initiating DNA single-strand breakage, with subsequent activation of the nuclear enzyme poly(ADP-ribose) synthetase, leading to eventual severe energy depletion of the cells and necrotic-type cell death. Antioxidant treatment inhibits the activation of poly(ADP-ribose) synthetase and prevents the organ injury associated with shock, inflammation, and ischemia/reperfusion.

Subfields: Immunology, Pathology and Forensic Medicine, Physiology

View Paper: https://www.semanticscholar.org/paper/0352602a655fadb6ed0d8d1fc9c7f2344f5a231e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. P. Barnes

In Pathology and Forensic Medicine

1. C. Oyinbo

In Physiology

1. Soheila Karimi-Abdolrezaee
2. P. Barnes
3. Antonio Ceriello
4. Arsalan Alizadeh
5. Scott Dyck

Citations in the corpus

• Pathophysiology and pharmacologic treatment of acute spinal cord injury. (2004, background): “respiratory chain enzymes, alter DNA and DNA-associated proteins and inhibit sodium-potassium ATPase, collectively conspiring to induce the metabolic collapse and subsequent necrotic or apoptotic death of the cell [26].”
• Acute Spinal Cord Injury, Part I: Pathophysiologic Mechanisms (2001, background): “Such reperfusion may exacerbate injury and cellular death through the genesis of deleterious free radicals and other toxic byproducts (37,38).”
• Traumatic Spinal Cord Injury: An Overview of Pathophysiology, Models and Acute Injury Mechanisms (2019, background): “Lipid and protein oxidation following SCI has a number of detrimental consequences at cellular level including mitochondrial respiratory and metabolic failure as well as DNA alteration that ultimately lead to cell death (141).”
• The physiology and pathophysiology of nitric oxide in the brain. (2005, background): “Oxidative stress plays a key role in ischemic-reperfusion situations (Cuzzocrea et al., 2001).”
• Mediators of Chronic Obstructive Pulmonary Disease (2004, background): “Currently available antioxidants are rather weak, but more potent drugs, including spin-trap antioxidants (nitrones) and stable glutathione analogs, are currently in clinical development (Cuzzocrea et al., 2001).”
• Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. (2011, background): “Ischemia and reperfusion induced endothelial damage are mediated through free radicals and other toxic byproducts (Cuzzocrea et al. 2001).”
• Biological activities of sulfated polysaccharides from tropical seaweeds. (2010, background): “These include cardiovascular disease, inflammatory conditions and neurodegenerative disease such as Alzheimer’s disease, mutations and cancer [21,22].”
• New insights on oxidative stress and diabetic complications may lead to a "causal" antioxidant therapy. (2003, background): “On this matter, it has recently been suggested that antioxidant therapy with vitamin E or other antioxidants is limited to scavenging already-formed oxidants and may therefore be considered a more “symptomatic” rather than a causal treatment for vascular oxidative stress (54).”