Search

The proopiomelanocortin-derived tridecapeptide alpha-melanocyte-stimulating hormone (alpha-MSH) is a neuropeptide that exerts broad anti-inflammatory actions in mammals. This study aimed to investigate the effect of alpha-MSH on ethanol-induced gastric ulcer in rats and to evaluate the involvement of endogenous somatostatin in the actions of the peptide. The rats received 1 mL 75% ethanol or saline orally. alpha-MSH was given (25 micro g/rat; i.p.) alone or following the somatostatin antagonist cyclo-(7-aminoheptanoyl-PH-E-d-Trp-Lys-THR) (10 microM/kg; i.p.) administration. Gastric lesions were scored macroscopically and microscopically following decapitation at 30 min after ethanol challenge. Gastric malondialdehyde (MDA) level, myeloperoxidase (MPO) activity and mast cell counts were assessed. Ethanol-induced gastric hemorrhagic lesions were characterized by increased gastric MDA level, MPO activity and mast cell counts. alpha-MSH treatment decreased the extent of tissue injury and reversed tissue MDA level, MPO activity and mast cell counts. The effect of the peptide on the severity of gastric lesions, MDA level and MPO activity was reversed by the somatostatin antagonist. In conclusion, alpha-MSH is beneficial in a rat model of gastric ulcer via mechanisms which partly involve the endogenous somatostatin.

Documentation concerning the pathogenesis of gastric hemorrhagic ulcer in Salmonella typhimurium (Salmonella typhi)-infective disease is lacking. This research first proposed that alterations of mast cell histamine release, gastric acid back-diffusion and mucosal microvascular permeability are important in modulating gastric ulcer and hemorrhage in Salmonella typhi-infected rats. Additionally, effects of several histamine-related drugs on this ulcer model were evaluated. Male Wistar rats were deprived food for 36 h. Live cultures of Salmonella typhi (OU 5045, 1 x 10(10) CFU in 1.0 mL of sterilized phosphate buffer saline) were challenged, intrajejunally to rats just before withdrawal of food. Control rats received the same volume of sterilized vehicle only. 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 hemoglobin content and ulcer areas were determined. Severe gastric hemorrhage and mucosal ulcerations, particularly in acidic stomachs, were observed in Salmonella typhi-infected rats. A positive correlation of histamine to gastric hemorrhage and ulcer was found in those rats with Salmonella typhi-infection. This hemorrhagic ulcer in Salmonella typhi-infected rats was effectively ameliorated by intraperitoneal ketotifen, diphenhydramine and ranitidine but was worsen by exogenous histamine or diamine oxidase. In conclusion, enhancement of acid back-diffusion, mast cell histamine release and microvascular permeability is important in modulating gastric hemorrhage and ulcer in Salmonella typhi-infected rats.