Ibuprofen decreases spontaneous activity and enhances nerve-evoked contractions to minimize mitomycin c-induced bladder dysfunction

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

Inflammation may play a causal role in urological side effects reported following intravesical mitomycin C (MMC). Our aim was to investigate the effects of the nonsteroidal anti-inflammatory drug ibuprofen (IBU) on the cytotoxic potency of MMC and the potential for IBU to protect against bladder dysfunction. Malignant (RT4, T24) and normal (UROtsa) urothelial lines were treated with MMC followed by ibuprofen, with cell viability and caspase-3 activity assessed. Female C57BL/6JArc mice (Saline/Control, MMC, Saline 1 IBU, and MMC 1 IBU) received intravesical treatment (1 hour) with saline or MMC (2 mg/ml), with IBU (1 mg/ml) delivered in drinking water (for 7 days). Voiding pattern analysis was conducted prior to and following (1, 3, 7 days) treatment. A whole-bladder preparation was used to assess compliance, contractile responses, and urothelial-mediator release. Ibuprofen selectively increased the cytotoxic potency of MMC and caspase-3 activity in both malignant cells lines but not in UROtsa. MMC significantly increased voiding frequency at 24 hours and 3 days, whereas administration of ibuprofen significantly reduced this effect. MMC significantly increased the frequency of spontaneous contractions from 2.3 6 0.5 contractions/min in saline controls to 4.8 6 0.16 contractions/min, with ibuprofen protecting against this change. Interestingly, although nerve-evoked responses were not altered by MMC, they were increased in both IBU groups. Ibuprofen improved voiding dysfunction following MMC treatment by reducing spontaneous phasic activity and enhancing nerve-mediated contractions. Ibuprofen use in bladder cancer patients may help to minimize the urological adverse effects associated with intravesical MMC.

Original languageEnglish
Pages (from-to)282-290
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume366
Issue number2
Early online date21 May 2018
DOIs
Publication statusPublished - 1 Aug 2018

Fingerprint

Ibuprofen
Mitomycin
Urinary Bladder
Caspase 3
Inbred C57BL Mouse
Urinary Bladder Neoplasms
Drinking Water
Compliance
Cell Survival
Anti-Inflammatory Agents
Therapeutics

Cite this

@article{43e8f0f94d014278982369120d66dbcb,
title = "Ibuprofen decreases spontaneous activity and enhances nerve-evoked contractions to minimize mitomycin c-induced bladder dysfunction",
abstract = "Inflammation may play a causal role in urological side effects reported following intravesical mitomycin C (MMC). Our aim was to investigate the effects of the nonsteroidal anti-inflammatory drug ibuprofen (IBU) on the cytotoxic potency of MMC and the potential for IBU to protect against bladder dysfunction. Malignant (RT4, T24) and normal (UROtsa) urothelial lines were treated with MMC followed by ibuprofen, with cell viability and caspase-3 activity assessed. Female C57BL/6JArc mice (Saline/Control, MMC, Saline 1 IBU, and MMC 1 IBU) received intravesical treatment (1 hour) with saline or MMC (2 mg/ml), with IBU (1 mg/ml) delivered in drinking water (for 7 days). Voiding pattern analysis was conducted prior to and following (1, 3, 7 days) treatment. A whole-bladder preparation was used to assess compliance, contractile responses, and urothelial-mediator release. Ibuprofen selectively increased the cytotoxic potency of MMC and caspase-3 activity in both malignant cells lines but not in UROtsa. MMC significantly increased voiding frequency at 24 hours and 3 days, whereas administration of ibuprofen significantly reduced this effect. MMC significantly increased the frequency of spontaneous contractions from 2.3 6 0.5 contractions/min in saline controls to 4.8 6 0.16 contractions/min, with ibuprofen protecting against this change. Interestingly, although nerve-evoked responses were not altered by MMC, they were increased in both IBU groups. Ibuprofen improved voiding dysfunction following MMC treatment by reducing spontaneous phasic activity and enhancing nerve-mediated contractions. Ibuprofen use in bladder cancer patients may help to minimize the urological adverse effects associated with intravesical MMC.",
author = "West, {Eliza G.} and Ryan Lang and Donna Sellers and Russ Chess-Williams and Catherine McDermott",
note = "The American Society for Pharmacology and Experimental Therapeutics.",
year = "2018",
month = "8",
day = "1",
doi = "10.1124/jpet.118.248989",
language = "English",
volume = "366",
pages = "282--290",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS",
number = "2",

}

TY - JOUR

T1 - Ibuprofen decreases spontaneous activity and enhances nerve-evoked contractions to minimize mitomycin c-induced bladder dysfunction

AU - West, Eliza G.

AU - Lang, Ryan

AU - Sellers, Donna

AU - Chess-Williams, Russ

AU - McDermott, Catherine

N1 - The American Society for Pharmacology and Experimental Therapeutics.

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Inflammation may play a causal role in urological side effects reported following intravesical mitomycin C (MMC). Our aim was to investigate the effects of the nonsteroidal anti-inflammatory drug ibuprofen (IBU) on the cytotoxic potency of MMC and the potential for IBU to protect against bladder dysfunction. Malignant (RT4, T24) and normal (UROtsa) urothelial lines were treated with MMC followed by ibuprofen, with cell viability and caspase-3 activity assessed. Female C57BL/6JArc mice (Saline/Control, MMC, Saline 1 IBU, and MMC 1 IBU) received intravesical treatment (1 hour) with saline or MMC (2 mg/ml), with IBU (1 mg/ml) delivered in drinking water (for 7 days). Voiding pattern analysis was conducted prior to and following (1, 3, 7 days) treatment. A whole-bladder preparation was used to assess compliance, contractile responses, and urothelial-mediator release. Ibuprofen selectively increased the cytotoxic potency of MMC and caspase-3 activity in both malignant cells lines but not in UROtsa. MMC significantly increased voiding frequency at 24 hours and 3 days, whereas administration of ibuprofen significantly reduced this effect. MMC significantly increased the frequency of spontaneous contractions from 2.3 6 0.5 contractions/min in saline controls to 4.8 6 0.16 contractions/min, with ibuprofen protecting against this change. Interestingly, although nerve-evoked responses were not altered by MMC, they were increased in both IBU groups. Ibuprofen improved voiding dysfunction following MMC treatment by reducing spontaneous phasic activity and enhancing nerve-mediated contractions. Ibuprofen use in bladder cancer patients may help to minimize the urological adverse effects associated with intravesical MMC.

AB - Inflammation may play a causal role in urological side effects reported following intravesical mitomycin C (MMC). Our aim was to investigate the effects of the nonsteroidal anti-inflammatory drug ibuprofen (IBU) on the cytotoxic potency of MMC and the potential for IBU to protect against bladder dysfunction. Malignant (RT4, T24) and normal (UROtsa) urothelial lines were treated with MMC followed by ibuprofen, with cell viability and caspase-3 activity assessed. Female C57BL/6JArc mice (Saline/Control, MMC, Saline 1 IBU, and MMC 1 IBU) received intravesical treatment (1 hour) with saline or MMC (2 mg/ml), with IBU (1 mg/ml) delivered in drinking water (for 7 days). Voiding pattern analysis was conducted prior to and following (1, 3, 7 days) treatment. A whole-bladder preparation was used to assess compliance, contractile responses, and urothelial-mediator release. Ibuprofen selectively increased the cytotoxic potency of MMC and caspase-3 activity in both malignant cells lines but not in UROtsa. MMC significantly increased voiding frequency at 24 hours and 3 days, whereas administration of ibuprofen significantly reduced this effect. MMC significantly increased the frequency of spontaneous contractions from 2.3 6 0.5 contractions/min in saline controls to 4.8 6 0.16 contractions/min, with ibuprofen protecting against this change. Interestingly, although nerve-evoked responses were not altered by MMC, they were increased in both IBU groups. Ibuprofen improved voiding dysfunction following MMC treatment by reducing spontaneous phasic activity and enhancing nerve-mediated contractions. Ibuprofen use in bladder cancer patients may help to minimize the urological adverse effects associated with intravesical MMC.

UR - http://www.scopus.com/inward/record.url?scp=85050394399&partnerID=8YFLogxK

U2 - 10.1124/jpet.118.248989

DO - 10.1124/jpet.118.248989

M3 - Article

VL - 366

SP - 282

EP - 290

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 2

ER -