Development of NSAIDs with lower gastric side effect

Tohru Mizushima

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

The anti-inflammatory action of nonsteroidal anti-inflammatory drugs (NSAIDs) is mediated through their inhibitory effects on cyclooxygenase (COX) activity. On the other hand, NSAIDs use is associated with gastrointestinal complications. The inhibition of COX by NSAIDs is not the sole explanation for the gastrointestinal side effects of NSAIDs. In this article, I review our recent work on the COX-independent mechanism involved in NSAID-induced gastric lesions. Using DNA microarray analysis, we found that NSAIDs affect expression of various genes in a COX-independent manner and found that membrane permeabilization activity of NSAIDs and resulting NSAID-induced apoptosis are involved in NSAID-induced gastric lesions. These results suggest that NSAIDs with lower membrane permeabilization activity would be safer on stomach tissue and we found that loxoprofen, a clinically used NSAID, has relatively lower membrane permeabilization activity than other NSAIDs. We synthesized derivatives of loxoprofen and found that fluoro-loxoprofen has lower membrane permeabilization activity and their oral administration produced fewer gastric lesions but showed an equivalent anti-inflammatory effect. These results suggest that fluoro-loxoprofen is likely to be therapeutically beneficial as safer NSAIDs.

Original languageEnglish
Title of host publicationFrontiers of Gastrointestinal Research
Pages71-78
Number of pages8
Volume30
DOIs
Publication statusPublished - 2012 Jun

Publication series

NameFrontiers of Gastrointestinal Research
Volume30
ISSN (Print)03020665
ISSN (Electronic)16623754

Fingerprint

Stomach
Anti-Inflammatory Agents
Pharmaceutical Preparations
Prostaglandin-Endoperoxide Synthases
Gastrointestinal Agents
Membranes
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Oral Administration
Apoptosis
Gene Expression

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Mizushima, T. (2012). Development of NSAIDs with lower gastric side effect. In Frontiers of Gastrointestinal Research (Vol. 30, pp. 71-78). (Frontiers of Gastrointestinal Research; Vol. 30). https://doi.org/10.1159/000338396

Development of NSAIDs with lower gastric side effect. / Mizushima, Tohru.

Frontiers of Gastrointestinal Research. Vol. 30 2012. p. 71-78 (Frontiers of Gastrointestinal Research; Vol. 30).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Mizushima, T 2012, Development of NSAIDs with lower gastric side effect. in Frontiers of Gastrointestinal Research. vol. 30, Frontiers of Gastrointestinal Research, vol. 30, pp. 71-78. https://doi.org/10.1159/000338396
Mizushima T. Development of NSAIDs with lower gastric side effect. In Frontiers of Gastrointestinal Research. Vol. 30. 2012. p. 71-78. (Frontiers of Gastrointestinal Research). https://doi.org/10.1159/000338396
Mizushima, Tohru. / Development of NSAIDs with lower gastric side effect. Frontiers of Gastrointestinal Research. Vol. 30 2012. pp. 71-78 (Frontiers of Gastrointestinal Research).
@inproceedings{712d1e16ca85460c8af2689d48810f4b,
title = "Development of NSAIDs with lower gastric side effect",
abstract = "The anti-inflammatory action of nonsteroidal anti-inflammatory drugs (NSAIDs) is mediated through their inhibitory effects on cyclooxygenase (COX) activity. On the other hand, NSAIDs use is associated with gastrointestinal complications. The inhibition of COX by NSAIDs is not the sole explanation for the gastrointestinal side effects of NSAIDs. In this article, I review our recent work on the COX-independent mechanism involved in NSAID-induced gastric lesions. Using DNA microarray analysis, we found that NSAIDs affect expression of various genes in a COX-independent manner and found that membrane permeabilization activity of NSAIDs and resulting NSAID-induced apoptosis are involved in NSAID-induced gastric lesions. These results suggest that NSAIDs with lower membrane permeabilization activity would be safer on stomach tissue and we found that loxoprofen, a clinically used NSAID, has relatively lower membrane permeabilization activity than other NSAIDs. We synthesized derivatives of loxoprofen and found that fluoro-loxoprofen has lower membrane permeabilization activity and their oral administration produced fewer gastric lesions but showed an equivalent anti-inflammatory effect. These results suggest that fluoro-loxoprofen is likely to be therapeutically beneficial as safer NSAIDs.",
author = "Tohru Mizushima",
year = "2012",
month = "6",
doi = "10.1159/000338396",
language = "English",
isbn = "9783318021837",
volume = "30",
series = "Frontiers of Gastrointestinal Research",
pages = "71--78",
booktitle = "Frontiers of Gastrointestinal Research",

}

TY - GEN

T1 - Development of NSAIDs with lower gastric side effect

AU - Mizushima, Tohru

PY - 2012/6

Y1 - 2012/6

N2 - The anti-inflammatory action of nonsteroidal anti-inflammatory drugs (NSAIDs) is mediated through their inhibitory effects on cyclooxygenase (COX) activity. On the other hand, NSAIDs use is associated with gastrointestinal complications. The inhibition of COX by NSAIDs is not the sole explanation for the gastrointestinal side effects of NSAIDs. In this article, I review our recent work on the COX-independent mechanism involved in NSAID-induced gastric lesions. Using DNA microarray analysis, we found that NSAIDs affect expression of various genes in a COX-independent manner and found that membrane permeabilization activity of NSAIDs and resulting NSAID-induced apoptosis are involved in NSAID-induced gastric lesions. These results suggest that NSAIDs with lower membrane permeabilization activity would be safer on stomach tissue and we found that loxoprofen, a clinically used NSAID, has relatively lower membrane permeabilization activity than other NSAIDs. We synthesized derivatives of loxoprofen and found that fluoro-loxoprofen has lower membrane permeabilization activity and their oral administration produced fewer gastric lesions but showed an equivalent anti-inflammatory effect. These results suggest that fluoro-loxoprofen is likely to be therapeutically beneficial as safer NSAIDs.

AB - The anti-inflammatory action of nonsteroidal anti-inflammatory drugs (NSAIDs) is mediated through their inhibitory effects on cyclooxygenase (COX) activity. On the other hand, NSAIDs use is associated with gastrointestinal complications. The inhibition of COX by NSAIDs is not the sole explanation for the gastrointestinal side effects of NSAIDs. In this article, I review our recent work on the COX-independent mechanism involved in NSAID-induced gastric lesions. Using DNA microarray analysis, we found that NSAIDs affect expression of various genes in a COX-independent manner and found that membrane permeabilization activity of NSAIDs and resulting NSAID-induced apoptosis are involved in NSAID-induced gastric lesions. These results suggest that NSAIDs with lower membrane permeabilization activity would be safer on stomach tissue and we found that loxoprofen, a clinically used NSAID, has relatively lower membrane permeabilization activity than other NSAIDs. We synthesized derivatives of loxoprofen and found that fluoro-loxoprofen has lower membrane permeabilization activity and their oral administration produced fewer gastric lesions but showed an equivalent anti-inflammatory effect. These results suggest that fluoro-loxoprofen is likely to be therapeutically beneficial as safer NSAIDs.

UR - http://www.scopus.com/inward/record.url?scp=84863758416&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863758416&partnerID=8YFLogxK

U2 - 10.1159/000338396

DO - 10.1159/000338396

M3 - Conference contribution

AN - SCOPUS:84863758416

SN - 9783318021837

VL - 30

T3 - Frontiers of Gastrointestinal Research

SP - 71

EP - 78

BT - Frontiers of Gastrointestinal Research

ER -