Ethanol-induced jejunal microvascular and morphological injury in relation to histamine release in rabbits.

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.