Evaluation of the protection of rat gastric mucosa by a prostaglandin analogue using cellular enzyme marker and histologic techniques.
Damage to the rat gastric mucosa after oral administration of ethanol and the effect of pretreatment with a prostaglandin analogue has been evaluated using histologic and enzyme-marker techniques. Rat whole stomachs were incubated in vitro and the intraluminal release of the cytoplasmic enzyme lactate dehydrogenase and the lysosomal enzymes acid phosphatase and beta-glucuronidase was determined by spectrophotometric techniques. Ethanol irrigation in vivo for 10 min significantly elevated the subsequent intraluminal release of both cytoplasmic and lysosomal enzymes in vitro. Pretreatment with 16,16-dimethyl prostaglandin E2 (0.1-1.25 microgram/kg p.o.) in doses that substantially inhibited the formation of macroscopically apparent necrotic lesions failed to prevent enzyme release. However, higher doses of the prostaglandin analogue (2.5-20 micrograms/kg) did significantly reduce the intraluminal release of the cellular enzymes, with the lysosomal enzymes being more readily inhibited. Histologic studies confirmed that the lower doses of the prostanoid prevented deep tissue necrosis and vasocongestion, yet did not protect surface epithelial cells from ethanol-induced damage. However, with the highest dose of 16,16-dimethyl prostaglandin E2 (20 micrograms/kg) a significant reduction in the extent of damage to the superficial epithelial cells was observed, suggesting a correlation with the findings using enzyme markers of cell damage. The apparent protective mechanisms of this prostanoid under the present conditions may involve mucus and fluid effusion that could allow restitution of the surface epithelial layer.
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D003593:Cytoplasm / Q000201:enzymology; D000431:Ethanol / Q000037:antagonists & inhibitors; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D005966:Glucuronidase / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D009336:Necrosis / Q000139:chemically induced / Q000201:enzymology; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011459:Prostaglandins E, Synthetic; D000431:Ethanol; D007770:L-Lactate Dehydrogenase; D000135:Acid Phosphatase; D005966:Glucuronidase; D015064:16,16-Dimethylprostaglandin E2; D007213:Indomethacin