Effects of the novel non-peptidyl low molecular weight radical scavenger IAC in different models of inflammation: a new perspective in anti- inflammatory therapy
| Autor: | Lorenzo Corsi |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Parkinson's disease
neurological disorders L-arginine bis (1-hydroxy-2 RNS Pharmacology guanosine triphosphate (GTP) medicine.disease_cause Biochemistry Lipid peroxidation chemistry.chemical_compound Mice Neuroprotective Properties Piperidines sclerosis hydrophylic-ity/lipophylicity Drug Discovery neurodegenerative diseases electron paramagnetic reso-nance (EPR) FREE RADICALS biology intrinsic property nitric oxide synthase Chemistry c-Jun N-terminal kinase (JNK) protein kinase C (PKC) IAC maladaptive re-sponse Anti-Inflammatory Agents Non-Steroidal ROS Free Radical Scavengers Alzheimer's disease superoxide dismutase nitrosative stress Neuroprotection cyclooxygenase myeloperoxidase Molecular Medicine PGE2 superoxide metalloproteinase medicine.symptom leukocyte gastrointesti-nal (GI) excitotoxicity kappa B kinase (IKK-b) Free Radicals medicine.drug_class Inflammatory bowel dis-eases (IBD) 6-tetramethyl-4-piperidinyl)-decandioate Radical Scavenger Inflammation Lipid Peroxidation 2 6 re-active oxygen nitrogen species nitric oxide (NO) non steroidal anti-inflammatory drugs (NSAIDs) prostaglandins (PGs) dysregulated peroxyl peroxynitrite radicals oxidative stress status xanthine oxidase mitogen-activated protein kinase (p38-MAPK) monocyte chemo-attractant protein-1 (MCP-1) vascular cell adhesion molecule-1 (VCAM-1) guanosine diphosphate (GDP) deoxyribo-nucleic acid (DNA) L-citrulline indomethacin gastric ulcers pancreatic islets reactive oxygen species (ROS) bilateral common carotid artery occlusion (BCCO) Anti-inflammatory Nitric oxide Superoxide dismutase medicine Animals Humans Organic Chemistry Rats biology.protein Cyclooxygenase Oxidative stress |
| Zdroj: | Current medicinal chemistry. 17(32) |
| ISSN: | 1875-533X |
| Popis: | 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 PGE 2 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. |
| Databáze: | OpenAIRE |
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