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Pharmaceuticals 2010, 3(5), 1614-1636; doi:10.3390/ph3051614

Molecular Mechanism for Various Pharmacological Activities of NSAIDS

Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan
Received: 10 December 2009 / Revised: 29 April 2010 / Accepted: 11 May 2010 / Published: 25 May 2010
(This article belongs to the Special Issue Non-Steroidal Anti-Inflammatory Drugs)
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The anti-inflammatory action of non-steroidal anti-inflammatory drugs (NSAIDs) is mediated through their inhibitory effects on cyclooxygenase (COX) activity. On the other hand, NSAID use is often associated with gastrointestinal complications. The inhibition of COX by NSAIDs is not the sole explanation for the gastrointestinal side effects of NSAIDs. Furthermore, recent epidemiological studies have revealed that prolonged NSAID use reduces the risk of cancer and Alzheimer’s disease (AD) and a COX-independent unknown mechanism is suggested to be involved in these activities of NSAIDs. In this article, I review our recent work on the COX-independent mechanism involved in NSAID-induced gastric lesions and anti-tumor and anti-AD activities of NSAIDs. Using DNA microarray analysis, we found that NSAIDs affect expression of various genes in a COX-independent manner. We found that membrane permeabilization activity of NSAIDs and resulting NSAID-induced apoptosis are involved in NSAID-induced gastric lesions. On the other hand, induction of expression of tight junction-related genes and endoplasmic reticulum chaperones were suggested to be involved in anti-tumor and anti-AD, respectively, activities of NSAIDs. These results suggest that NSAIDs affect expression of various genes in a COX-independent manner, which is involved in various pharmacological activities of NSAIDs. View Full-Text
Keywords: NSAIDs; gastric ulcer; gene expression; cancer; Alzheimer’s disease NSAIDs; gastric ulcer; gene expression; cancer; Alzheimer’s disease

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This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Mizushima, T. Molecular Mechanism for Various Pharmacological Activities of NSAIDS. Pharmaceuticals 2010, 3, 1614-1636.

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