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  • 1
    ISSN: 1573-2568
    Keywords: cytoprotection ; histology ; ethanol ; prostaglandin ; antiulcer drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The capacity for cytoprotection has been claimed for a number of drugs that may have a place in the treatment of peptic ulcer disease. In this study we have used quantitative histological criteria to evaluate the ability of these drugs to be cytoprotective and have compared their effects with that of natural prostaglandin E2 (PG). The standard rat model, with injury by instillation of 1 ml of absolute ethanol, has been used. Putative cytoprotective agents were administered 15 min prior to ethanol. Each animal was sacrificed 15 min after ethanol exposure. The stomach was removed and studied using an established quantitative histological technique. This technique provides a measure of the surface area of mucosa damaged and of the volume of mucosa damaged. Ethanol alone caused damage to 76% of the area of the rat stomach and 14% of the volume of the rat gastric mucosa. Pretreatment by PG (25 μg/ml) resulted in reduction of the area of damage to 45% and reduction of the percentage volume damage to 2.2%. The synthetic analog of PGE2, Enprostil (1 μg/ml) achieved similar protective effects. With pretreatment with colloidal bismuth subcitrate (10 mg/kg) or sucralfate (25 mg/kg), no protection against the surface area damaged by ethanol was seen, but there was a marked reduction of the volume of mucosa damaged. Indomethacin pretreatment augmented the damage caused by ethanol. The protective effects of colloidal bismuth subcitrate and sucralfate were not blocked by pretreatment with indomethacin. The histamine H2-receptor antagonists cimetidine and ranitidine, the substituted benzimadazole compound omeprazole, and the antimuscarinic drug pirenzepine did not exhibit any cytoprotective effect in this study.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Digestive diseases and sciences 36 (1991), S. 1353-1360 
    ISSN: 1573-2568
    Keywords: cytoprotection ; microcirculation ; sucralfate ; prostaglandin E2 ; colloidal bismuth subcitrate ; ischemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prostaglandin E2 (PGE2), colloidal bismuth subcitrate (CBS), and sucralfate (SUC) are known to protect the gastric mucosa from ethanol injury. The proposed central role for the microcirculation in gastric mucosal defense and as a site for the expression of the protective effects of these agents was investigated in the rat stomach. Animals were pretreated with either PGE2, CBS, or SUC. Control rats were given normal saline. After allowing 15 min for expression of the pretreatment, ethanol was administered as a 10%, 25%, 50% or 100% solution to groups of rats with normally perfused stomach and to other groups of rats in whom the stomach was made ischemic by cross-clamping the supracoeliac aorta immediately prior to the instillation of ethanol. The extent of gastric mucosal damage was measured using quantitative histological techniques and expressed as a percentage of surface area and volume of mucosa damaged. In the presence of ischemia, the extent of damage by ethanol was markedly increased, with total destruction of the mucosa by the 50% and 100% solutions. With 25% ethanol, the volume of mucosal damage was increased from 0.5% in the normally perfused stomach to 53.5% with ischemia. When 10% ethanol was instilled into the ischemic stomach, only 0.8% of the volume of the mucosa was damaged, which was not different from the volume of mucosa damaged after the ischemic stomach was exposed to normal saline alone (1.0%). Pretreatment with PGE2, CBS, or SUC did not significantly change the extent of damage seen with exposure of the ischemic stomach to 25% or 50% ethanol. These results show that the absence of normal mucosal microvascular perfusion markedly increases the extent of damage by ethanol and that, in the absence of microvascular flow, the protective effects of PGE2, CBS, and SUC are not expressed. These findings support the proposal that a primary component of the protective action of these agents is the, maintenance of the integrity of the mucosal microvasculature.
    Type of Medium: Electronic Resource
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