Effects of delayed NSAID administration after experimental eccentric contraction injury - A cellular and proteomics study.

BACKGROUND:Acute muscle injuries are exceedingly common and non-steroidal anti-inflammatory drugs (NSAIDs) are widely consumed to reduce the associated inflammation, swelling and pain that peak 1-2 days post-injury. While prophylactic use or early administration of NSAIDs has been shown to delay mus...

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Main Authors: Amy E Bryant, Michael J Aldape, Clifford R Bayer, Eva J Katahira, Laura Bond, Carrie D Nicora, Thomas L Fillmore, Therese R W Clauss, Thomas O Metz, Bobbie-Jo Webb-Robertson, Dennis L Stevens
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5330483?pdf=render
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author Amy E Bryant
Michael J Aldape
Clifford R Bayer
Eva J Katahira
Laura Bond
Carrie D Nicora
Thomas L Fillmore
Therese R W Clauss
Thomas O Metz
Bobbie-Jo Webb-Robertson
Dennis L Stevens
author_facet Amy E Bryant
Michael J Aldape
Clifford R Bayer
Eva J Katahira
Laura Bond
Carrie D Nicora
Thomas L Fillmore
Therese R W Clauss
Thomas O Metz
Bobbie-Jo Webb-Robertson
Dennis L Stevens
author_sort Amy E Bryant
collection DOAJ
description BACKGROUND:Acute muscle injuries are exceedingly common and non-steroidal anti-inflammatory drugs (NSAIDs) are widely consumed to reduce the associated inflammation, swelling and pain that peak 1-2 days post-injury. While prophylactic use or early administration of NSAIDs has been shown to delay muscle regeneration and contribute to loss of muscle strength after healing, little is known about the effects of delayed NSAID use. Further, NSAID use following non-penetrating injury has been associated with increased risk and severity of infection, including that due to group A streptococcus, though the mechanisms remain to be elucidated. The present study investigated the effects of delayed NSAID administration on muscle repair and sought mechanisms supporting an injury/NSAID/infection axis. METHODS:A murine model of eccentric contraction (EC)-induced injury of the tibialis anterior muscle was used to profile the cellular and molecular changes induced by ketorolac tromethamine administered 47 hr post injury. RESULTS:NSAID administration inhibited several important muscle regeneration processes and down-regulated multiple cytoprotective proteins known to inhibit the intrinsic pathway of programmed cell death. These activities were associated with increased caspase activity in injured muscles but were independent of any NSAID effect on macrophage influx or phenotype switching. CONCLUSIONS:These findings provide new molecular evidence supporting the notion that NSAIDs have a direct negative influence on muscle repair after acute strain injury in mice and thus add to renewed concern about the safety and benefits of NSAIDS in both children and adults, in those with progressive loss of muscle mass such as the elderly or patients with cancer or AIDS, and those at risk of secondary infection after trauma or surgery.
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spelling doaj.art-debe4290161745cba72e49bf78a41bbd2022-12-22T03:58:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01122e017248610.1371/journal.pone.0172486Effects of delayed NSAID administration after experimental eccentric contraction injury - A cellular and proteomics study.Amy E BryantMichael J AldapeClifford R BayerEva J KatahiraLaura BondCarrie D NicoraThomas L FillmoreTherese R W ClaussThomas O MetzBobbie-Jo Webb-RobertsonDennis L StevensBACKGROUND:Acute muscle injuries are exceedingly common and non-steroidal anti-inflammatory drugs (NSAIDs) are widely consumed to reduce the associated inflammation, swelling and pain that peak 1-2 days post-injury. While prophylactic use or early administration of NSAIDs has been shown to delay muscle regeneration and contribute to loss of muscle strength after healing, little is known about the effects of delayed NSAID use. Further, NSAID use following non-penetrating injury has been associated with increased risk and severity of infection, including that due to group A streptococcus, though the mechanisms remain to be elucidated. The present study investigated the effects of delayed NSAID administration on muscle repair and sought mechanisms supporting an injury/NSAID/infection axis. METHODS:A murine model of eccentric contraction (EC)-induced injury of the tibialis anterior muscle was used to profile the cellular and molecular changes induced by ketorolac tromethamine administered 47 hr post injury. RESULTS:NSAID administration inhibited several important muscle regeneration processes and down-regulated multiple cytoprotective proteins known to inhibit the intrinsic pathway of programmed cell death. These activities were associated with increased caspase activity in injured muscles but were independent of any NSAID effect on macrophage influx or phenotype switching. CONCLUSIONS:These findings provide new molecular evidence supporting the notion that NSAIDs have a direct negative influence on muscle repair after acute strain injury in mice and thus add to renewed concern about the safety and benefits of NSAIDS in both children and adults, in those with progressive loss of muscle mass such as the elderly or patients with cancer or AIDS, and those at risk of secondary infection after trauma or surgery.http://europepmc.org/articles/PMC5330483?pdf=render
spellingShingle Amy E Bryant
Michael J Aldape
Clifford R Bayer
Eva J Katahira
Laura Bond
Carrie D Nicora
Thomas L Fillmore
Therese R W Clauss
Thomas O Metz
Bobbie-Jo Webb-Robertson
Dennis L Stevens
Effects of delayed NSAID administration after experimental eccentric contraction injury - A cellular and proteomics study.
PLoS ONE
title Effects of delayed NSAID administration after experimental eccentric contraction injury - A cellular and proteomics study.
title_full Effects of delayed NSAID administration after experimental eccentric contraction injury - A cellular and proteomics study.
title_fullStr Effects of delayed NSAID administration after experimental eccentric contraction injury - A cellular and proteomics study.
title_full_unstemmed Effects of delayed NSAID administration after experimental eccentric contraction injury - A cellular and proteomics study.
title_short Effects of delayed NSAID administration after experimental eccentric contraction injury - A cellular and proteomics study.
title_sort effects of delayed nsaid administration after experimental eccentric contraction injury a cellular and proteomics study
url http://europepmc.org/articles/PMC5330483?pdf=render
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