Paraaminosalicylate blocks that ileal injury induced by phorbol myristate acetate

Michael C. Overdahl, Mark W. Julian, Steven E. Weisbrode, W. Bruce Davis, Paul M. Dorinsky

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Activation of neutrophils with the release of oxidant radicals has been implicated in the pathogenesis of gut injury in inflammatory bowel disease (IBD). The pathogenesis of gut injury in the multiple organ dysfunction syndrome associated with acute lung injury, although less focal, appears to be similar. Paraaminosalicylate (PAS) has been shown to be effective in treating IBD, most likely because of its ability to scavenge oxidant radicals. The present study was therefore designed to test the hypothesis that PAS attenuates the gut injury typically seen during systemic neutrophil activation by phorbol myristate acetate (PMA). We assessed gut injury by measuring the concentration ratio of lymph to plasma protein (C(L)/C(P)) at steady-state lymph flows in autoperfused cat ileum preparations. As expected, the C(L)/C(P) increased in animals given PMA (15 μg/kb; n = 6) compared with control animals (n = 5) (0.205 ± 0.033 versus 0.118 ± 0.004; p = 0.04) and were accompanied by morphologic alterations. In contrast, the intravenous administration of PAS (100 mg/kg) to animals prior to PMA infusion (n = 5) yielded a C(L)/C(P) value indistinguishable from that in control animals (0.113 ± 0.017 versus 0.118 ± 0.004). Additional in vitro studies suggested that the protective effects of PAS were not the result of altered neutrophil margination, chemotaxis, or oxidant burst. Although PAS appeared to protect the ileum from PMA-induced microvascular injury, it had no protective effects on the lungs.

Original languageEnglish (US)
Pages (from-to)1640-1647
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume149
Issue number6
DOIs
StatePublished - Jan 1 1994

Fingerprint

Tetradecanoylphorbol Acetate
Oxidants
Wounds and Injuries
Neutrophil Activation
Lymph
Ileum
Inflammatory Bowel Diseases
Aptitude
Multiple Organ Failure
Acute Lung Injury
Chemotaxis
Protein C
Intravenous Administration
Blood Proteins
Cats
Neutrophils
Lung

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Paraaminosalicylate blocks that ileal injury induced by phorbol myristate acetate. / Overdahl, Michael C.; Julian, Mark W.; Weisbrode, Steven E.; Davis, W. Bruce; Dorinsky, Paul M.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 149, No. 6, 01.01.1994, p. 1640-1647.

Research output: Contribution to journalArticle

Overdahl, Michael C. ; Julian, Mark W. ; Weisbrode, Steven E. ; Davis, W. Bruce ; Dorinsky, Paul M. / Paraaminosalicylate blocks that ileal injury induced by phorbol myristate acetate. In: American Journal of Respiratory and Critical Care Medicine. 1994 ; Vol. 149, No. 6. pp. 1640-1647.
@article{cecc43fcea7f43509a83d602a9edc9b8,
title = "Paraaminosalicylate blocks that ileal injury induced by phorbol myristate acetate",
abstract = "Activation of neutrophils with the release of oxidant radicals has been implicated in the pathogenesis of gut injury in inflammatory bowel disease (IBD). The pathogenesis of gut injury in the multiple organ dysfunction syndrome associated with acute lung injury, although less focal, appears to be similar. Paraaminosalicylate (PAS) has been shown to be effective in treating IBD, most likely because of its ability to scavenge oxidant radicals. The present study was therefore designed to test the hypothesis that PAS attenuates the gut injury typically seen during systemic neutrophil activation by phorbol myristate acetate (PMA). We assessed gut injury by measuring the concentration ratio of lymph to plasma protein (C(L)/C(P)) at steady-state lymph flows in autoperfused cat ileum preparations. As expected, the C(L)/C(P) increased in animals given PMA (15 μg/kb; n = 6) compared with control animals (n = 5) (0.205 ± 0.033 versus 0.118 ± 0.004; p = 0.04) and were accompanied by morphologic alterations. In contrast, the intravenous administration of PAS (100 mg/kg) to animals prior to PMA infusion (n = 5) yielded a C(L)/C(P) value indistinguishable from that in control animals (0.113 ± 0.017 versus 0.118 ± 0.004). Additional in vitro studies suggested that the protective effects of PAS were not the result of altered neutrophil margination, chemotaxis, or oxidant burst. Although PAS appeared to protect the ileum from PMA-induced microvascular injury, it had no protective effects on the lungs.",
author = "Overdahl, {Michael C.} and Julian, {Mark W.} and Weisbrode, {Steven E.} and Davis, {W. Bruce} and Dorinsky, {Paul M.}",
year = "1994",
month = "1",
day = "1",
doi = "10.1164/ajrccm.149.6.8004323",
language = "English (US)",
volume = "149",
pages = "1640--1647",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "6",

}

TY - JOUR

T1 - Paraaminosalicylate blocks that ileal injury induced by phorbol myristate acetate

AU - Overdahl, Michael C.

AU - Julian, Mark W.

AU - Weisbrode, Steven E.

AU - Davis, W. Bruce

AU - Dorinsky, Paul M.

PY - 1994/1/1

Y1 - 1994/1/1

N2 - Activation of neutrophils with the release of oxidant radicals has been implicated in the pathogenesis of gut injury in inflammatory bowel disease (IBD). The pathogenesis of gut injury in the multiple organ dysfunction syndrome associated with acute lung injury, although less focal, appears to be similar. Paraaminosalicylate (PAS) has been shown to be effective in treating IBD, most likely because of its ability to scavenge oxidant radicals. The present study was therefore designed to test the hypothesis that PAS attenuates the gut injury typically seen during systemic neutrophil activation by phorbol myristate acetate (PMA). We assessed gut injury by measuring the concentration ratio of lymph to plasma protein (C(L)/C(P)) at steady-state lymph flows in autoperfused cat ileum preparations. As expected, the C(L)/C(P) increased in animals given PMA (15 μg/kb; n = 6) compared with control animals (n = 5) (0.205 ± 0.033 versus 0.118 ± 0.004; p = 0.04) and were accompanied by morphologic alterations. In contrast, the intravenous administration of PAS (100 mg/kg) to animals prior to PMA infusion (n = 5) yielded a C(L)/C(P) value indistinguishable from that in control animals (0.113 ± 0.017 versus 0.118 ± 0.004). Additional in vitro studies suggested that the protective effects of PAS were not the result of altered neutrophil margination, chemotaxis, or oxidant burst. Although PAS appeared to protect the ileum from PMA-induced microvascular injury, it had no protective effects on the lungs.

AB - Activation of neutrophils with the release of oxidant radicals has been implicated in the pathogenesis of gut injury in inflammatory bowel disease (IBD). The pathogenesis of gut injury in the multiple organ dysfunction syndrome associated with acute lung injury, although less focal, appears to be similar. Paraaminosalicylate (PAS) has been shown to be effective in treating IBD, most likely because of its ability to scavenge oxidant radicals. The present study was therefore designed to test the hypothesis that PAS attenuates the gut injury typically seen during systemic neutrophil activation by phorbol myristate acetate (PMA). We assessed gut injury by measuring the concentration ratio of lymph to plasma protein (C(L)/C(P)) at steady-state lymph flows in autoperfused cat ileum preparations. As expected, the C(L)/C(P) increased in animals given PMA (15 μg/kb; n = 6) compared with control animals (n = 5) (0.205 ± 0.033 versus 0.118 ± 0.004; p = 0.04) and were accompanied by morphologic alterations. In contrast, the intravenous administration of PAS (100 mg/kg) to animals prior to PMA infusion (n = 5) yielded a C(L)/C(P) value indistinguishable from that in control animals (0.113 ± 0.017 versus 0.118 ± 0.004). Additional in vitro studies suggested that the protective effects of PAS were not the result of altered neutrophil margination, chemotaxis, or oxidant burst. Although PAS appeared to protect the ileum from PMA-induced microvascular injury, it had no protective effects on the lungs.

UR - http://www.scopus.com/inward/record.url?scp=0028233244&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028233244&partnerID=8YFLogxK

U2 - 10.1164/ajrccm.149.6.8004323

DO - 10.1164/ajrccm.149.6.8004323

M3 - Article

C2 - 8004323

AN - SCOPUS:0028233244

VL - 149

SP - 1640

EP - 1647

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 6

ER -