Ethanol stimulates formation of leukotriene C4 in rat gastric mucosa

doi:10.1016/0090-6980(86)90054-7

Prostaglandins

Volume 31, Issue 2, February 1986, Pages 283-293

Prostaglandins

https://doi.org/10.1016/0090-6980(86)90054-7 Get rights and content

Abstract

Ethanol-induced gastric mucosal damage is characterized by microcirculatory changes such as statis and plasma leakage. Sluggish blood flow and statis have also been observed after administration of exogenous leukotriene (LT) C₄. The effect of ethanol on the release of LTC₄ from rat gastric mucosa was therefore investigated. It was found that intragastric instillation of ethanol increases gastric mucosal release of LTC₄ in a dose- and time-dependent manner parallel to the production of gastric lesions. The lipoxugenase inhibitor nordihydroguaiaretic acid (NDGA) and the anti-ulcer drug carbenoxolone (CX) inhibited mucosal release of LTC₄ and simultaneously protected against gastric damage caused by ethanol. It is concluded that increased formation of LTC₄ and /or other 5-lipoxygenase-derived products of arachidonate metabolism may be involved in ethanol-induced gastric damage. Furthermore, inhibition of the 5-lipoxygenase pathway may be an important mechanism of action of gastric protective drugs.

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Ethanol is known to increase gastric injury through acute hemorrhagic lesions, mucosal edema, erosion and ulceration (Sagradas et al., 2015). The acute effects are attributed to solubilization of the protective mucus, protein precipitation of the cytoplasmic components in the superficial cells of the gastric mucosa, the release of vasoactive mediators such as leukotrienes C4 (LTC4) and histamine, and the release of inhibitors of mucosal prostaglandins (Peskar, Lange, Hoppe, & Peskar, 1986). Alcohol may also increase the flow of sodium and potassium into the lumen, increase pepsin release, and decrease the tissue levels of nucleic acids and proteins.
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In the model of ethanol-induced gastric damage, hecogenin at the higher dose showed a gastroprotective effect similar to that observed with ranitidine and NAC, used as reference drugs. This model was shown to be associated with a significant reduction in NP-SH contents in the gastric mucosa, as well as with other mechanisms, such as the mucosal leukotriene release (Peskar et al., 1986) and submucosa venular constriction (Oates and Hakkinen, 1988). The NP-SH compounds exert their functions in gastroprotection by maintaining the integrity of the mucosal barrier and binding free radicals formed (Szabo and Vattay, 1990).
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Ethanol stimulates formation of leukotriene C4 in rat gastric mucosa

Abstract

Gastroenterology

Gastroenterology

Biochim. Biophys. Acta

Prostaglandins

Biochem. Pharmac.

Prostaglandins

Gastric vasoconstrictor actions of leukotriene C4, PGF2α, and thromboxane mimetic U-46619 on rat submucosal microcirculation in vivo

Am. J. Physiol.

Stimulation of rat gastric mucosal leukotriene formation by ethanol

Naunyn-Schmiedeberg's Arch. Pharmacol.

Effects of exogenous prostaglandins on the release of leukotriene C4-like immunoreactivity and on coronary flow in indomethacin-treated anaphylactic guinea-pig hearts

Naunyn-Schmiedeberg's Arch. Pharmacol.

Ethanol stimulates formation of leukotriene C₄ in rat gastric mucosa

Gastric vasoconstrictor actions of leukotriene C₄, PGF_2α, and thromboxane mimetic U-46619 on rat submucosal microcirculation in vivo

Effects of exogenous prostaglandins on the release of leukotriene C₄-like immunoreactivity and on coronary flow in indomethacin-treated anaphylactic guinea-pig hearts