Flavonoid-induced gastroprotection in rats: Role of blood flow and leukocyte adherence

Marion A. Blank, Beth L. Ems, Linda M. O'Brien, Pamela S. Weisshaar, Jeffrey J. Ares, Peter W. Abel, Donna Marie McCafferty, John L. Wallace

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

To elucidate the mechanisms of flavonoid-induced protection against nonsteroidal anti-inflammatory drug (indomethacin)-induced acute gastric damage, the effects of 5-methoxyflavone and 5-methoxyflavanone on the gastric vasculature were compared both in vivo (using laser Doppler flowmetry in anesthetized rats) and in vitro on rat superior mesenteric arteries. The effects of the compounds on indomethacin-induced leukocyte adherence to mesenteric venules were investigated by intravital videomicroscopy. Oral 5-methoxyflavone reduced indomethacin-induced macroscopic damage by 38 to 99% (ED50 5.5 mg/kg). Damage was not significantly reduced by 5-methoxyflavanone. Light microscopy studies also demonstrated a reduction in damage severity. 5-Methoxyflavone, but not 5-methoxyflavanone, increased the gastric conductance significantly. The effects on isolated mesenteric arteries correlated with the effects on in vivo conductance. Finally, indomethacin-induced leukocyte adherence was inhibited to a greater extent by 5-methoxyflavone than by 5-methoxyflavanone. In conclusion, the flavonoid 5-methoxyflavone provides gastroprotection against nonsteroidal anti-inflammatory drug-induced gastric damage. A structurally similar compound, 5-methoxyflavanone, demonstrated minimal gastroprotective activity, suggesting that the double bond of 5-methoxyflavone is required for biological activity. The finding that 5-methoxyflavone (but not 5-methoxyflavanone) significantly increased gastric vascular perfusion and reduced leukocyte adherence to mesenteric venules suggests that these mechanisms may contribute to the flavonoid's gastroprotective activity.

Original languageEnglish
Pages (from-to)147-154
Number of pages8
JournalDigestion
Volume58
Issue number2
StatePublished - Mar 1997

Fingerprint

Flavonoids
Indomethacin
Stomach
Leukocytes
Venules
Anti-Inflammatory Agents
Gastrointestinal Agents
Video Microscopy
Laser-Doppler Flowmetry
Mesenteric Arteries
Superior Mesenteric Artery
Blood Vessels
Microscopy
Perfusion
Light
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Blank, M. A., Ems, B. L., O'Brien, L. M., Weisshaar, P. S., Ares, J. J., Abel, P. W., ... Wallace, J. L. (1997). Flavonoid-induced gastroprotection in rats: Role of blood flow and leukocyte adherence. Digestion, 58(2), 147-154.

Flavonoid-induced gastroprotection in rats : Role of blood flow and leukocyte adherence. / Blank, Marion A.; Ems, Beth L.; O'Brien, Linda M.; Weisshaar, Pamela S.; Ares, Jeffrey J.; Abel, Peter W.; McCafferty, Donna Marie; Wallace, John L.

In: Digestion, Vol. 58, No. 2, 03.1997, p. 147-154.

Research output: Contribution to journalArticle

Blank, MA, Ems, BL, O'Brien, LM, Weisshaar, PS, Ares, JJ, Abel, PW, McCafferty, DM & Wallace, JL 1997, 'Flavonoid-induced gastroprotection in rats: Role of blood flow and leukocyte adherence', Digestion, vol. 58, no. 2, pp. 147-154.
Blank MA, Ems BL, O'Brien LM, Weisshaar PS, Ares JJ, Abel PW et al. Flavonoid-induced gastroprotection in rats: Role of blood flow and leukocyte adherence. Digestion. 1997 Mar;58(2):147-154.
Blank, Marion A. ; Ems, Beth L. ; O'Brien, Linda M. ; Weisshaar, Pamela S. ; Ares, Jeffrey J. ; Abel, Peter W. ; McCafferty, Donna Marie ; Wallace, John L. / Flavonoid-induced gastroprotection in rats : Role of blood flow and leukocyte adherence. In: Digestion. 1997 ; Vol. 58, No. 2. pp. 147-154.
@article{07d0852f2c4b46b2a7a4bc733cb2cc41,
title = "Flavonoid-induced gastroprotection in rats: Role of blood flow and leukocyte adherence",
abstract = "To elucidate the mechanisms of flavonoid-induced protection against nonsteroidal anti-inflammatory drug (indomethacin)-induced acute gastric damage, the effects of 5-methoxyflavone and 5-methoxyflavanone on the gastric vasculature were compared both in vivo (using laser Doppler flowmetry in anesthetized rats) and in vitro on rat superior mesenteric arteries. The effects of the compounds on indomethacin-induced leukocyte adherence to mesenteric venules were investigated by intravital videomicroscopy. Oral 5-methoxyflavone reduced indomethacin-induced macroscopic damage by 38 to 99{\%} (ED50 5.5 mg/kg). Damage was not significantly reduced by 5-methoxyflavanone. Light microscopy studies also demonstrated a reduction in damage severity. 5-Methoxyflavone, but not 5-methoxyflavanone, increased the gastric conductance significantly. The effects on isolated mesenteric arteries correlated with the effects on in vivo conductance. Finally, indomethacin-induced leukocyte adherence was inhibited to a greater extent by 5-methoxyflavone than by 5-methoxyflavanone. In conclusion, the flavonoid 5-methoxyflavone provides gastroprotection against nonsteroidal anti-inflammatory drug-induced gastric damage. A structurally similar compound, 5-methoxyflavanone, demonstrated minimal gastroprotective activity, suggesting that the double bond of 5-methoxyflavone is required for biological activity. The finding that 5-methoxyflavone (but not 5-methoxyflavanone) significantly increased gastric vascular perfusion and reduced leukocyte adherence to mesenteric venules suggests that these mechanisms may contribute to the flavonoid's gastroprotective activity.",
author = "Blank, {Marion A.} and Ems, {Beth L.} and O'Brien, {Linda M.} and Weisshaar, {Pamela S.} and Ares, {Jeffrey J.} and Abel, {Peter W.} and McCafferty, {Donna Marie} and Wallace, {John L.}",
year = "1997",
month = "3",
language = "English",
volume = "58",
pages = "147--154",
journal = "Digestion",
issn = "0012-2823",
publisher = "S. Karger AG",
number = "2",

}

TY - JOUR

T1 - Flavonoid-induced gastroprotection in rats

T2 - Role of blood flow and leukocyte adherence

AU - Blank, Marion A.

AU - Ems, Beth L.

AU - O'Brien, Linda M.

AU - Weisshaar, Pamela S.

AU - Ares, Jeffrey J.

AU - Abel, Peter W.

AU - McCafferty, Donna Marie

AU - Wallace, John L.

PY - 1997/3

Y1 - 1997/3

N2 - To elucidate the mechanisms of flavonoid-induced protection against nonsteroidal anti-inflammatory drug (indomethacin)-induced acute gastric damage, the effects of 5-methoxyflavone and 5-methoxyflavanone on the gastric vasculature were compared both in vivo (using laser Doppler flowmetry in anesthetized rats) and in vitro on rat superior mesenteric arteries. The effects of the compounds on indomethacin-induced leukocyte adherence to mesenteric venules were investigated by intravital videomicroscopy. Oral 5-methoxyflavone reduced indomethacin-induced macroscopic damage by 38 to 99% (ED50 5.5 mg/kg). Damage was not significantly reduced by 5-methoxyflavanone. Light microscopy studies also demonstrated a reduction in damage severity. 5-Methoxyflavone, but not 5-methoxyflavanone, increased the gastric conductance significantly. The effects on isolated mesenteric arteries correlated with the effects on in vivo conductance. Finally, indomethacin-induced leukocyte adherence was inhibited to a greater extent by 5-methoxyflavone than by 5-methoxyflavanone. In conclusion, the flavonoid 5-methoxyflavone provides gastroprotection against nonsteroidal anti-inflammatory drug-induced gastric damage. A structurally similar compound, 5-methoxyflavanone, demonstrated minimal gastroprotective activity, suggesting that the double bond of 5-methoxyflavone is required for biological activity. The finding that 5-methoxyflavone (but not 5-methoxyflavanone) significantly increased gastric vascular perfusion and reduced leukocyte adherence to mesenteric venules suggests that these mechanisms may contribute to the flavonoid's gastroprotective activity.

AB - To elucidate the mechanisms of flavonoid-induced protection against nonsteroidal anti-inflammatory drug (indomethacin)-induced acute gastric damage, the effects of 5-methoxyflavone and 5-methoxyflavanone on the gastric vasculature were compared both in vivo (using laser Doppler flowmetry in anesthetized rats) and in vitro on rat superior mesenteric arteries. The effects of the compounds on indomethacin-induced leukocyte adherence to mesenteric venules were investigated by intravital videomicroscopy. Oral 5-methoxyflavone reduced indomethacin-induced macroscopic damage by 38 to 99% (ED50 5.5 mg/kg). Damage was not significantly reduced by 5-methoxyflavanone. Light microscopy studies also demonstrated a reduction in damage severity. 5-Methoxyflavone, but not 5-methoxyflavanone, increased the gastric conductance significantly. The effects on isolated mesenteric arteries correlated with the effects on in vivo conductance. Finally, indomethacin-induced leukocyte adherence was inhibited to a greater extent by 5-methoxyflavone than by 5-methoxyflavanone. In conclusion, the flavonoid 5-methoxyflavone provides gastroprotection against nonsteroidal anti-inflammatory drug-induced gastric damage. A structurally similar compound, 5-methoxyflavanone, demonstrated minimal gastroprotective activity, suggesting that the double bond of 5-methoxyflavone is required for biological activity. The finding that 5-methoxyflavone (but not 5-methoxyflavanone) significantly increased gastric vascular perfusion and reduced leukocyte adherence to mesenteric venules suggests that these mechanisms may contribute to the flavonoid's gastroprotective activity.

UR - http://www.scopus.com/inward/record.url?scp=0030896739&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030896739&partnerID=8YFLogxK

M3 - Article

C2 - 9144304

AN - SCOPUS:0030896739

VL - 58

SP - 147

EP - 154

JO - Digestion

JF - Digestion

SN - 0012-2823

IS - 2

ER -