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Effects of the Novel Non-Peptidyl Low Molecular Weight Radical Scavenger IAC in Different Models of Inflammation: A New Perspective in Anti-Inflammatory Therapy

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Abstract:

The bis (1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate called IAC, is a new non-peptidyl low molecular weight radical scavenger able to give a fast reaction with the majority of radical species involved in the oxidative stress. This intrinsic property might be of particular interest in all the processes where it presents an over production of reactive oxygen/nitrogen species (ROS/RNS) such as inflammation. Indeed, it is well known that systemic inflammatory response is associated with the production of ROS, nitric oxide (NO), which in turn deplete the endogenous GSH, mediating cytotoxicity. It has been shown that IAC through its antioxidant activity, exerted a protective effect in vitro in islets isolated from type-2 diabetic patients, and in vivo in a non-obese diabetic mouse model and in DNBS-induced colitis in rats. The ability of IAC to protect brain from ischemia, suggests a possible use of the compound in broad range of inflammatory- related diseases. It is well known that the use of non steroidal anti-inflammatory drugs (NSAIDs) is associated with a broad spectrum of untoward side-effects such as gastrointestinal ulceration. The major pathogenetic element in the development of these effects is the depletion of prostaglandins (PGs) through inhibition of cyclooxygenase. The evidence that IAC protects gastric mucosa in an animal model of indomethacin-induced ulcer, through local increase of PGE2 levels and antioxidant activity, candidates this compound as a novel, promising, anti-inflammatory compound avoiding the major common untoward side-effects elicited by NSAID's.





Keywords: Alzheimer's disease; FREE RADICALS; IAC; Inflammation; Inflammatory bowel dis-eases (IBD); L-arginine; L-citrulline; Lipid Peroxidation; Neuroprotection; Neuroprotective Properties; PGE2; Parkinson's disease; RNS; ROS; Radical Scavenger; bilateral common carotid artery occlusion (BCCO); bis (1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate; c-Jun N-terminal kinase (JNK); cyclooxygenase; deoxyribo-nucleic acid (DNA); dysregulated; electron paramagnetic reso-nance (EPR); excitotoxicity; gastric ulcers; gastrointesti-nal (GI); guanosine diphosphate (GDP); guanosine triphosphate (GTP); hydrophylic-ity/lipophylicity; indomethacin; intrinsic property; kappa B kinase (IKK-b); leukocyte; maladaptive re-sponse; metalloproteinase; mitogen-activated protein kinase (p38-MAPK); monocyte chemo-attractant protein-1 (MCP-1); myeloperoxidase; neurodegenerative diseases; neurological disorders; nitric oxide (NO); nitric oxide synthase; nitrogen species; nitrosative stress; non steroidal anti-inflammatory drugs (NSAIDs); oxidative stress status; pancreatic islets; peroxyl, superoxide; peroxynitrite radicals; prostaglandins (PGs); protein kinase C (PKC); re-active oxygen; reactive oxygen species (ROS); sclerosis; superoxide dismutase; vascular cell adhesion molecule-1 (VCAM-1); xanthine oxidase

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986710793205390

Publication date: November 1, 2010

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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