Mucosal blood flow stasis and hypoxemia as the pathogenesis of acute gastric mucosal injury: role of endogenous leukotrienes and prostaglandins.
To clarify the roles of endogenous leukotrienes and prostaglandins in the ethanol-induced gastric mucosal injury, the effect of AA-861 (a selective 5-lipoxygenase inhibitor) and indomethacin (a cyclooxygenase inhibitor) on the ethanol-induced gastric mucosal lesions was investigated in fasted rats. Furthermore, the effect of these agents on the gastric mucosal microcirculatory disturbance induced by ethanol was also investigated using laser Doppler velocimetry and reflectance spectrophotometry. Forty percent ethanol caused mucosal microcirculatory stasis and mucosal hypoxemia, followed by mucosal injury. The pretreatment with AA-861 reduced the mucosal injury and significantly reduced the mucosal congestion and hypoxia induced by 40% ethanol. The pretreatment with indomethacin did not reduce the gastric mucosal damage or influence the mucosal blood flow stasis and the mucosal hypoxemia induced by ethanol. These results suggested that the increase of endogenous leukotrienes after intragastric administration of ethanol is responsible for the mucosal microcirculatory disturbance and mucosal tissue hypoxemia resulting in the mucosal injury, and that the decrease of prostaglandins alone may not play an important role in ethanol-induced mucosal injury.
First Department of Medicine, Osaka University Medical School, Japan.
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S
Tsuji
S
S
Kawano
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N
Sato
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T
Kamada
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D000431:Ethanol / Q000633:toxicity*; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D015289:Leukotrienes / Q000502:physiology*; D016859:Lipoxygenase Inhibitors; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D011292:Premedication; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D016227:Benzoquinones; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D011453:Prostaglandins; D000431:Ethanol; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D007213:Indomethacin