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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; in revised form: 29 April 2010 / Accepted: 11 May 2010 / Published: 25 May 2010
Abstract: 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.
Keywords: NSAIDs; gastric ulcer; gene expression; cancer; Alzheimer’s disease
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MDPI and ACS Style
Mizushima, T. Molecular Mechanism for Various Pharmacological Activities of NSAIDS. Pharmaceuticals 2010, 3, 1614-1636.
Mizushima T. Molecular Mechanism for Various Pharmacological Activities of NSAIDS. Pharmaceuticals. 2010; 3(5):1614-1636.
Mizushima, Tohru. 2010. "Molecular Mechanism for Various Pharmacological Activities of NSAIDS." Pharmaceuticals 3, no. 5: 1614-1636.