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Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury.
Pharmacol Rev. 2001 Mar; 53(1):135-59.PR

Abstract

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.

Authors+Show Affiliations

Institute of Pharmacology, University of Messina, Messina, Italy. salvator@www.unime.itNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

11171943

Citation

Cuzzocrea, S, et al. "Antioxidant Therapy: a New Pharmacological Approach in Shock, Inflammation, and Ischemia/reperfusion Injury." Pharmacological Reviews, vol. 53, no. 1, 2001, pp. 135-59.
Cuzzocrea S, Riley DP, Caputi AP, et al. Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. Pharmacol Rev. 2001;53(1):135-59.
Cuzzocrea, S., Riley, D. P., Caputi, A. P., & Salvemini, D. (2001). Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. Pharmacological Reviews, 53(1), 135-59.
Cuzzocrea S, et al. Antioxidant Therapy: a New Pharmacological Approach in Shock, Inflammation, and Ischemia/reperfusion Injury. Pharmacol Rev. 2001;53(1):135-59. PubMed PMID: 11171943.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. AU - Cuzzocrea,S, AU - Riley,D P, AU - Caputi,A P, AU - Salvemini,D, PY - 2001/2/15/pubmed PY - 2001/4/17/medline PY - 2001/2/15/entrez SP - 135 EP - 59 JF - Pharmacological reviews JO - Pharmacol Rev VL - 53 IS - 1 N2 - 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. SN - 0031-6997 UR - https://www.unboundmedicine.com/medline/citation/11171943/Antioxidant_therapy:_a_new_pharmacological_approach_in_shock_inflammation_and_ischemia/reperfusion_injury_ L2 - http://pharmrev.aspetjournals.org/cgi/pmidlookup?view=long&pmid=11171943 DB - PRIME DP - Unbound Medicine ER -