Roles of histamine receptors and oxyradicals in aggravation of acid-induced gastric haemorrhagic ulcers in endotoxaemic rats.

Abstract

We clarified the roles of histamine H(1)-, H(2)-, H(3)-receptors and oxyradicals in the exacerbation of acid-induced gastric haemorrhage and stomach ulcer in endotoxaemic rats by measuring changes in gastric mucosal glutathione concentrations, lipid peroxide generation and histamine levels as well as in luminal electrolytes and haemoglobin contents. Stomach ulcers were evaluated by morphological and histological examination. Rats were deprived of food for 24 h, and challenged intravenously with lipopolysaccharide (LPS, 3 mg/kg) at 0, 12, 18 and 24 h after withdrawal of food. Control rats received saline only. Gastric truncal vagotomy was performed and followed by irrigation for 3 h with an acid solution containing 100 mmol/L HC1 and 54 mmol/L NaCl. The augmentation of mucosal permeability to electrolytes (acid back-diffusion), haemoglobin contents and lipid peroxide levels as well as the lowered mucosal glutathione concentrations were dependent on the duration of LPS intoxication. Serious damage of corpus mucosal cells was observed in acid-perfused stomachs of LPS rats. Intraperitoneal diphenhydramine, an H(1)-receptor antagonist, or ranitidine, an H(2)-receptor blocker, caused dose-dependent inhibition of these ulcerogenic factors. Antioxidants, including ascorbate and sodium benzoate, also were effective in inhibition. Moreover, intraperitoneal R-(alpha)-methylhistamine, an H(3)-receptor agonist, produced elimination, while thioperamide, an H(3)-receptor antagonist, and exogenous histamine elevated mucosal histamine concentrations and haemorrhagic ulcers in LPS rats. It is concluded that gastric haemorrhage and stomach ulcers produced by acid solution in LPS-treated rats are modulated by oxyradicals and histamine H(1)-, H(2)- and H(3)-receptors.

• Authors: C R Hung, D Z Hsu
• Journal: Inflammopharmacology (Inflammopharmacology) Vol. 6 Issue 4 Pg. 339-55 ( 1998) ISSN: 0925-4692 [Print] Switzerland
• PMID: 17657630 (Publication Type: Journal Article)