The involvement of heme oxygenase-1 activity in the therapeutic actions of 5-aminosalicylic acid in rat colitis

Krisztina Horváth, C. Varga, A. Berkó, A. Pósa, F. László, Brendan J R Whittle

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

The mechanism of action of 5-aminosalicylic acid (5-ASA), the active therapeutic moiety of a number of clinically used anti-colitic agents, is unclear. The present study investigates whether the beneficial effects in vivo could involve induction of the heat shock protein, heme oxygenase-1 (HO-1), known to provide endogenous anti-oxidant and anti-inflammatory moieties which can modulate colonic inflammation. The effects of 5-ASA on the colonic expression and activity of HO-1 along with its effect on the inflammatory damage have been evaluated in the colitis provoked by instillation of trinitrobenzene sulphonic acid (TNBS) over 48 h in the rat. Intracolonic administration of 5-ASA (8, 25 and 75 mg/kg/day) dose-dependently reduced the TNBS-provoked macroscopic colonic inflammatory injury, myeloperoxidase (MPO) activity and TNF-α levels, while also dose-dependently increasing colonic heme oxygenase enzyme activity. Colonic HO-1 protein expression, determined by Western blot analysis in this colitis model, was likewise further induced by 5-ASA. Intracolonic administration of 5-ASA alone under unchallenged conditions also induced colonic HO-1 protein expression and stimulated heme oxygenase enzyme activity. Administration of zinc protoporphyrin (50 μmol/kg/day, s.c.), which prevented the increase in colonic heme oxygenase activity, abolished the anti-colitic effect of 5-ASA. These results suggest that 5-ASA may exert its colonic anti-oxidant and anti-inflammatory effects in vivo in part through the up-regulation of HO-1 enzyme expression and activity.

Original languageEnglish
Pages (from-to)315-323
Number of pages9
JournalEuropean Journal of Pharmacology
Volume581
Issue number3
DOIs
Publication statusPublished - Mar 10 2008

Fingerprint

Mesalamine
Heme Oxygenase-1
Colitis
Heme Oxygenase (Decyclizing)
Trinitrobenzenes
Sulfonic Acids
Oxidants
Therapeutics
Anti-Inflammatory Agents
Enzymes
Heat-Shock Proteins
Peroxidase
Proteins
Up-Regulation
Western Blotting
Inflammation
Wounds and Injuries

Keywords

  • 5-Aminosalicylic acid (5-ASA)
  • Aminosalicylates
  • Heme oxygenase-1 (HO-1)
  • Inflammatory bowel diseases
  • Mesalamine
  • Model of colitis
  • TNBS colitis
  • Trinitrobenzene sulphonic acid
  • Zinc protoporphyrin (ZnPP)

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

The involvement of heme oxygenase-1 activity in the therapeutic actions of 5-aminosalicylic acid in rat colitis. / Horváth, Krisztina; Varga, C.; Berkó, A.; Pósa, A.; László, F.; Whittle, Brendan J R.

In: European Journal of Pharmacology, Vol. 581, No. 3, 10.03.2008, p. 315-323.

Research output: Contribution to journalArticle

@article{ca356e06cb8e400d95b65e2b5a7412ff,
title = "The involvement of heme oxygenase-1 activity in the therapeutic actions of 5-aminosalicylic acid in rat colitis",
abstract = "The mechanism of action of 5-aminosalicylic acid (5-ASA), the active therapeutic moiety of a number of clinically used anti-colitic agents, is unclear. The present study investigates whether the beneficial effects in vivo could involve induction of the heat shock protein, heme oxygenase-1 (HO-1), known to provide endogenous anti-oxidant and anti-inflammatory moieties which can modulate colonic inflammation. The effects of 5-ASA on the colonic expression and activity of HO-1 along with its effect on the inflammatory damage have been evaluated in the colitis provoked by instillation of trinitrobenzene sulphonic acid (TNBS) over 48 h in the rat. Intracolonic administration of 5-ASA (8, 25 and 75 mg/kg/day) dose-dependently reduced the TNBS-provoked macroscopic colonic inflammatory injury, myeloperoxidase (MPO) activity and TNF-α levels, while also dose-dependently increasing colonic heme oxygenase enzyme activity. Colonic HO-1 protein expression, determined by Western blot analysis in this colitis model, was likewise further induced by 5-ASA. Intracolonic administration of 5-ASA alone under unchallenged conditions also induced colonic HO-1 protein expression and stimulated heme oxygenase enzyme activity. Administration of zinc protoporphyrin (50 μmol/kg/day, s.c.), which prevented the increase in colonic heme oxygenase activity, abolished the anti-colitic effect of 5-ASA. These results suggest that 5-ASA may exert its colonic anti-oxidant and anti-inflammatory effects in vivo in part through the up-regulation of HO-1 enzyme expression and activity.",
keywords = "5-Aminosalicylic acid (5-ASA), Aminosalicylates, Heme oxygenase-1 (HO-1), Inflammatory bowel diseases, Mesalamine, Model of colitis, TNBS colitis, Trinitrobenzene sulphonic acid, Zinc protoporphyrin (ZnPP)",
author = "Krisztina Horv{\'a}th and C. Varga and A. Berk{\'o} and A. P{\'o}sa and F. L{\'a}szl{\'o} and Whittle, {Brendan J R}",
year = "2008",
month = "3",
day = "10",
doi = "10.1016/j.ejphar.2007.12.004",
language = "English",
volume = "581",
pages = "315--323",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "3",

}

TY - JOUR

T1 - The involvement of heme oxygenase-1 activity in the therapeutic actions of 5-aminosalicylic acid in rat colitis

AU - Horváth, Krisztina

AU - Varga, C.

AU - Berkó, A.

AU - Pósa, A.

AU - László, F.

AU - Whittle, Brendan J R

PY - 2008/3/10

Y1 - 2008/3/10

N2 - The mechanism of action of 5-aminosalicylic acid (5-ASA), the active therapeutic moiety of a number of clinically used anti-colitic agents, is unclear. The present study investigates whether the beneficial effects in vivo could involve induction of the heat shock protein, heme oxygenase-1 (HO-1), known to provide endogenous anti-oxidant and anti-inflammatory moieties which can modulate colonic inflammation. The effects of 5-ASA on the colonic expression and activity of HO-1 along with its effect on the inflammatory damage have been evaluated in the colitis provoked by instillation of trinitrobenzene sulphonic acid (TNBS) over 48 h in the rat. Intracolonic administration of 5-ASA (8, 25 and 75 mg/kg/day) dose-dependently reduced the TNBS-provoked macroscopic colonic inflammatory injury, myeloperoxidase (MPO) activity and TNF-α levels, while also dose-dependently increasing colonic heme oxygenase enzyme activity. Colonic HO-1 protein expression, determined by Western blot analysis in this colitis model, was likewise further induced by 5-ASA. Intracolonic administration of 5-ASA alone under unchallenged conditions also induced colonic HO-1 protein expression and stimulated heme oxygenase enzyme activity. Administration of zinc protoporphyrin (50 μmol/kg/day, s.c.), which prevented the increase in colonic heme oxygenase activity, abolished the anti-colitic effect of 5-ASA. These results suggest that 5-ASA may exert its colonic anti-oxidant and anti-inflammatory effects in vivo in part through the up-regulation of HO-1 enzyme expression and activity.

AB - The mechanism of action of 5-aminosalicylic acid (5-ASA), the active therapeutic moiety of a number of clinically used anti-colitic agents, is unclear. The present study investigates whether the beneficial effects in vivo could involve induction of the heat shock protein, heme oxygenase-1 (HO-1), known to provide endogenous anti-oxidant and anti-inflammatory moieties which can modulate colonic inflammation. The effects of 5-ASA on the colonic expression and activity of HO-1 along with its effect on the inflammatory damage have been evaluated in the colitis provoked by instillation of trinitrobenzene sulphonic acid (TNBS) over 48 h in the rat. Intracolonic administration of 5-ASA (8, 25 and 75 mg/kg/day) dose-dependently reduced the TNBS-provoked macroscopic colonic inflammatory injury, myeloperoxidase (MPO) activity and TNF-α levels, while also dose-dependently increasing colonic heme oxygenase enzyme activity. Colonic HO-1 protein expression, determined by Western blot analysis in this colitis model, was likewise further induced by 5-ASA. Intracolonic administration of 5-ASA alone under unchallenged conditions also induced colonic HO-1 protein expression and stimulated heme oxygenase enzyme activity. Administration of zinc protoporphyrin (50 μmol/kg/day, s.c.), which prevented the increase in colonic heme oxygenase activity, abolished the anti-colitic effect of 5-ASA. These results suggest that 5-ASA may exert its colonic anti-oxidant and anti-inflammatory effects in vivo in part through the up-regulation of HO-1 enzyme expression and activity.

KW - 5-Aminosalicylic acid (5-ASA)

KW - Aminosalicylates

KW - Heme oxygenase-1 (HO-1)

KW - Inflammatory bowel diseases

KW - Mesalamine

KW - Model of colitis

KW - TNBS colitis

KW - Trinitrobenzene sulphonic acid

KW - Zinc protoporphyrin (ZnPP)

UR - http://www.scopus.com/inward/record.url?scp=38949193198&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38949193198&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2007.12.004

DO - 10.1016/j.ejphar.2007.12.004

M3 - Article

C2 - 18215658

AN - SCOPUS:38949193198

VL - 581

SP - 315

EP - 323

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 3

ER -