Elliott G, Whited B A, Purmalis A, Davis J P, Field S O, Lancaster C, Robert A
Life Sci. 1986 Aug 4;39(5):423-32. doi: 10.1016/0024-3205(86)90522-9.
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.
给大鼠口服单剂量1200毫克/千克的甲芬那酸，63%的动物出现肾乳头坏死（RPN）。口服剂量为0.75毫克/千克，每日三次的16,16 - 二甲基前列腺素E2（dmPGE2）可将发病率降至27%。RPN可能是由前列腺素环氧化酶抑制剂甲芬那酸引起的肾前列腺素耗竭所致。用dmPGE2替代可能通过防止前列腺素耗竭来降低RPN。我们得出结论，所使用的前列腺素对肾脏具有细胞保护作用。甲芬那酸与大多数非甾体类抗炎化合物（NOSAC）一样，会导致小肠（空肠和回肠）溃疡。这些溃疡可被dmPGE2预防（肠道细胞保护）。然而，与大多数其他NOSAC不同的是，甲芬那酸在几乎所有动物（80%）中都会导致十二指肠溃疡。在这些溃疡中，88%会穿孔。死亡的26只动物中有25只患有穿孔性溃疡。这些十二指肠溃疡也可被dmPGE2预防。甲芬那酸诱导的溃疡可用作测试具有预防或治愈十二指肠溃疡潜力药物的实验模型。
