Effect of 16, 16-dimethyl PGE 2 on renal papillary necrosis and gastrointestinal ulcerations (gastric, duodenal, intestinal) produced in rats by mefenamic acid

Abstract

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 PGE 2 (dmPGE 2), 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 dmPGE 2 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 dmPGE 2 (intestinal cytoprotection). Unlike most other NOSAC, however, mefanamic acid produced duodenal ulcers in nearly all animals (80%). Of these ulcers, 88% were perforared. Twenty-five of the twenty-six animals that died had a perforated ulcer. These duodenal ulcers were also prevented by dmPGE 2. Mefanamic acid-induced ulcers could be used as an experimental model for testing agents with a potential for preventing or healing duodenal ulcers.