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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Potential Therapeutic Effect of Antioxidant Therapy in Shock and Inflammation

Author(s): Salvatore Cuzzocrea, Christoph Thiemermann and Daniela Salvemini

Volume 11, Issue 9, 2004

Page: [1147 - 1162] Pages: 16

DOI: 10.2174/0929867043365396

Price: $65


Oxidative stress results from an oxidant / antioxidant imbalance, an excess of oxidants and / or a depletion of antioxidants. A considerable body of recent evidence suggests that oxidant stress plays a major role in several aspects of acute and chronic inflammation and is the subject of this review. Immunohistochemical and biochemical evidence demonstrate the significant role of reactive oxygen species (ROS) in acute and chronic inflammation. Initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3-phosphate dehydrogenase, inhibition of membrane Na+ / K+ ATP-ase activity, inactivation of membrane sodium channels, and other oxidative protein modifications contribute to the cytotoxic effect of ROS. All these toxicities are likely to play a role in the pathophysiology of shock, inflammation and ischemia and reperfusion. (2) Treatment with either peroxynitrite decomposition catalysts, which selectively inhibit peroxynitrite, or with SODms, which selectively mimic the catalytic activity of the human superoxide dismutase (SOD) enzymes, have been shown to prevent in vivo the delayed tissue injury and the cellular energetic failure associated with inflammation. 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 (PARS), leading to eventual severe energy depletion of the cells, and necrotic-type cell death. Antioxidant treatment inhibits the activation of PARS, and prevents the organ injury associated with acute and chronic inflammation.

Keywords: antioxidant therapy, shock, Inflammation, oxidant/antioxidant, reactive oxygen species

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