Molecular Mechanism for Various Pharmacological Activities of NSAIDS

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 explanat...

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Main Author: Tohru Mizushima
Format: Article
Language:English
Published: MDPI AG 2010-05-01
Series:Pharmaceuticals
Subjects:
Online Access:http://www.mdpi.com/1424-8247/3/5/1614/
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author Tohru Mizushima
author_facet Tohru Mizushima
author_sort Tohru Mizushima
collection DOAJ
description 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.
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spelling doaj.art-68212cb61e8741d390674e6356a585312022-12-22T01:23:31ZengMDPI AGPharmaceuticals1424-82472010-05-01351614163610.3390/ph3051614Molecular Mechanism for Various Pharmacological Activities of NSAIDSTohru MizushimaThe 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.http://www.mdpi.com/1424-8247/3/5/1614/NSAIDsgastric ulcergene expressioncancerAlzheimer’s disease
spellingShingle Tohru Mizushima
Molecular Mechanism for Various Pharmacological Activities of NSAIDS
Pharmaceuticals
NSAIDs
gastric ulcer
gene expression
cancer
Alzheimer’s disease
title Molecular Mechanism for Various Pharmacological Activities of NSAIDS
title_full Molecular Mechanism for Various Pharmacological Activities of NSAIDS
title_fullStr Molecular Mechanism for Various Pharmacological Activities of NSAIDS
title_full_unstemmed Molecular Mechanism for Various Pharmacological Activities of NSAIDS
title_short Molecular Mechanism for Various Pharmacological Activities of NSAIDS
title_sort molecular mechanism for various pharmacological activities of nsaids
topic NSAIDs
gastric ulcer
gene expression
cancer
Alzheimer’s disease
url http://www.mdpi.com/1424-8247/3/5/1614/
work_keys_str_mv AT tohrumizushima molecularmechanismforvariouspharmacologicalactivitiesofnsaids