Effect of 16,16-dimethyl PGE2 on renal papillary necrosis and gastrointestinal ulcerations (gastric, duodenal, intestinal) produced in rats by mefenamic acid.
Mefenamic acid, given orally to rats at a single dose of 1200 mg/kg, produced renal papillary necrosis (RPN) in 63% of animals. The incidence was reduced to 27% by 16,16-dimethyl PGE2 (dmPGE2), given at an oral dose of 0.75 mg/kg t.i.d. RPN is likely to be caused by the renal prostaglandin depletion elicited by mefenamic acid, an inhibitor of prostaglandin cyclooxygenase. Substitution with dmPGE2 reduces RPN presumably by preventing the prostaglandin depletion. We conclude that the prostaglandin used is cytoprotective for the kidney. Mefenamic acid, like most nonsteroidal anti-inflammatory compounds (NOSAC), produced ulcerations of the small intestine (jejunum and ileum). These were prevented by dmPGE2 (intestinal cytoprotection). Unlike most other NOSAC, however, mefenamic acid produced duodenal ulcers in nearly all animals (80%). Of these ulcers, 88% were perforated. Twenty-five of the twenty-six animals that died had a perforated ulcer. These duodenal ulcers were also prevented by dmPGE2. Mefenamic acid-induced ulcers could be used as an experimental model for testing agents with a potential for preventing or healing duodenal ulcers.
D015064:16,16-Dimethylprostaglandin E2 / Q000627:therapeutic use*; D000818:Animals; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D005260:Female; D007410:Intestinal Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007681:Kidney Papillary Necrosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008528:Mefenamic Acid; D011459:Prostaglandins E, Synthetic / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D011459:Prostaglandins E, Synthetic; D008528:Mefenamic Acid; D015064:16,16-Dimethylprostaglandin E2