Evaluation of putative cytoprotective properties of antiulcer drugs using quantitative histological techniques.
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 micrograms/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 microgram/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.(ABSTRACT TRUNCATED AT 250 WORDS)
O'Brien
P E
PE
Monash University Department of Surgery, Alfred Hospital, Prahran, Victoria, Australia.
Frydman
G
G
Holmes
R
R
Malcontenti
C
C
Phelan
D
D
D000818:Animals; D000863:Antacids / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D000431:Ethanol / Q000633:toxicity; D005753:Gastric Mucosa / Q000187:drug effects*; D009942:Organometallic Compounds / Q000494:pharmacology; D011292:Premedication; D051381:Rats; D013392:Sucralfate / Q000494:pharmacology
D000863:Antacids; D000897:Anti-Ulcer Agents; D009942:Organometallic Compounds; D000431:Ethanol; D013392:Sucralfate; C002791:bismuth tripotassium dicitrate; D015232:Dinoprostone