Role of histamine and acid back-diffusion in modulation of gastric microvascular permeability and haemorrhagic ulcers in betel-quid-fed rats

Evidence concerning the pathogenesis of gastric haemorrhagic ulcer produced by betel quid chewing (BQC) is lacking. This research first proposes that alterations of mast cell histamine release and gastric acid back-diffusion are important in modulating gastric microvascular permeability and mucosal haemorrhagic ulcer in BQC-fed rats. The effects of several histamine receptor antagonists on this ulcer model also were evaluated. Male Wistar rats were fed with BQC diet or normal pellet diet. After 1, 30 and 90 day(s), rat stomachs were irrigated for 3 h with either normal saline or simulated gastric juice. Gastric acid back-diffusion, mucosal histamine concentration, microvascular permeability, as well as luminal haemoglobin content and ulcer areas were determined. Severe gastric haemorrhage and mucosal ulcerations, particularly in acidic stomachs, were observed in BQC-fed rats. A high correlation was observed between histamine and gastric haemorrhage, as well as between acid back-diffusion and mucosal ulceration was found in rats fed with BQC. This haemorrhagic ulcer in BQC-fed rats was effectively ameliorated by intragastric ketotifen, ranitidine or their combination. In conclusion, enhancement of acid back-diffusion, mast cell histamine release and microvascular permeability is important in modulating gastric haemorrhage and ulcer in BQC-fed rats.