Histamine is involved in ethanol-induced jejunal microvascular injury in rabbits

doi:10.1016/0016-5085(88)90355-1

Gastroenterology

Volume 95, Issue 5, November 1988, Pages 1227-1233

https://doi.org/10.1016/0016-5085(88)90355-1 Get rights and content

Abstract

To examine for the possible involvement of histamine in the jejunal microvascular effects of ethanol, we investigated the effects of (a) intraluminal ethanol on histamine release by the jejunum and (b) simultaneous inhibition of both histamine₁ and histamine₂ receptors (using promethazine and cimetidine, respectively) on ethanol-induced intestinal plasma protein loss in rabbits. Ethanol increased histamine release by the jejunum both in vivo (p < 0.01) and in vitro (p < 0.05). To investigate the effect of antihistamines on ethanol-induced plasma protein loss, we determined the dose of blockers that would completely inhibit the histamine₁ and histamine₂ receptors. In the absence of antihistamines, ethanol caused a 10-fold increase in jejunal protein loss over the controls (p < 0.001). Simultaneous inhibition of histamine₁ and histamine₂ receptors attenuated (p < 0.025), but did not abolish, the ethanol-induced protein loss. These data are discussed in relation to the literature, and it is concluded that histamine may play a role in the jejunal microvascular effects of ethanol. As the ethanol-induced protein loss was not completely inhibited, other mediators or mechanisms were probably involved.

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Background: To investigate the relation between ethanol-induced jejunal microvascular injury, morphological changes, and histamine release, the present study examined whether the attenuation of microvascular effect of ethanol by 16,16-dimethyl prostaglandin E₂ (dmPGE₂) (reported by us previously) was associated with an attenuation of epithelial damage and histamine release. Methods: Rabbits were used. Mucosal microvascular injury was assessed by determining jejunal plasma protein loss (JPPL), histamine release by measuring histamine concentration of the gut effluent, and epithelial damage by routine histology. Results: (1) During 90-minute jejunal ethanol perfusion, there was a direct relation between the time course of histamine release and that of JPPL. (2) dmPGE₂ attenuated the ethanol-induced JPPL and histamine release, and the decrease in JPPL was directly proportional to the decrease in histamine release. (3) dmPGE₂ did not alleviate ethanol-induced epithelial damage. (4) Ketotifen (a mast cell stabilizer), similar to dmPGE₂, attenuated ethanol-induced JPPL and histamine release. (5) Ethanol caused histamine release by the jejunum in vitro; this was attenuated by dmPGE₂ and also by phloretin (a mast cell stabilizer). Conclusions: It appears that (1) ethanol causes JPPL by inducing release of mediators from mucosal mast cells. (2) dmPGE₂ attenuates JPPL by stabilizing mast cells. (3) The ethanol-induced mucosal microvascular injury is directly related to histamine release but not to epithelial damage.

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^*: This work was supported by grant MT. 4257 from the Medical Research Council of Canada.

¹: Dr. D. J. Leddin was the recipient of the Alexander Stewart Fellowship, Queen's University.

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Histamine is involved in ethanol-induced jejunal microvascular injury in rabbits*

Abstract

Am J Clin Nutr

Gastroenterology

Gastroenterology

J Biol Chem

Prostaglandins

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Clin Chim Acta

Gastroenterology

Microvasc Res

Microvasc Res

Microvasc Res

Villous damage induced by suction biopsy and by acute ethanol intake in the normal human small intestine

Dig Dis Sci

Effect of ethanol on morphology and total, capillary and shunted blood flow of the different anatomical layers of the dog jejunum

Dig Dis Sci