Rankin G O, Cressey-Veneziano K, Wang R T, Brown P I
J Appl Toxicol. 1986 Oct;6(5):349-56. doi: 10.1002/jat.2550060509.
Phensuximide is a succinimide antiepileptic drug useful in the treatment of petit mal epilepsy. Phensuximide has been reported to be nephrotoxic in man but not in animals. In the present study, the effects of single and subacute administration for seven days of phensuximide on renal function and urinary tract morphology were evaluated in Sprague-Dawley and Fischer 344 rats. Single administration of phensuximide (1.25 mmol/kg, ip) induced mild changes in renal function (trace hematuria, increased proteinuria and decreased p-aminohippurate uptake). No morphological changes were observed at 24 hr. Subacute administration of phensuximide (0.6 mmol/kg/day, ip) produced diuresis in the Sprague-Dawley rat, but little functional evidence of nephrotoxicity. Renal morphological changes in Sprague-Dawley rats were seen primarily in distal segments of the nephrons. These changes were characterized by distensions of the basal infoldings, apical protrusions, and occlusion of some lumen. In the Fischer 344 rat, subacute phensuximide administration (0.3 or 0.6 mmol/kg/day, ip) resulted in transient hematuria and proteinuria, but no change in the other renal function parameters studied. Renal morphological changes observed in Fischer 344 rats occurred primarily in proximal tubular cells. Damaged cells were characterized by large vacuoles at the basal infoldings, accumulations of opaque granules, migration of nuclei to the lumenal membranes, occlusion of the lumen and/or loss of the brush border. Morphological damage was more widespread in Fischer 344 rats than in Sprague-Dawley rats.(ABSTRACT TRUNCATED AT 250 WORDS)
甲琥胺是一种琥珀酰亚胺类抗癫痫药物，可用于治疗失神性癫痫。据报道，甲琥胺对人类有肾毒性，但对动物无此毒性。在本研究中，评估了甲琥胺单次给药及连续七天亚急性给药对斯普拉格-道利大鼠和费希尔344大鼠肾功能及尿路形态的影响。单次注射甲琥胺（1.25 mmol/kg，腹腔注射）引起肾功能轻度改变（微量血尿、蛋白尿增加和对氨基马尿酸摄取减少）。24小时时未观察到形态学变化。甲琥胺亚急性给药（0.6 mmol/kg/天，腹腔注射）使斯普拉格-道利大鼠产生利尿作用，但几乎没有肾毒性的功能证据。斯普拉格-道利大鼠的肾脏形态学变化主要见于肾单位的远端节段。这些变化的特征是基底襞扩张、顶端突出以及一些管腔闭塞。在费希尔344大鼠中，亚急性给予甲琥胺（0.3或0.6 mmol/kg/天，腹腔注射）导致短暂性血尿和蛋白尿，但所研究的其他肾功能参数无变化。在费希尔344大鼠中观察到的肾脏形态学变化主要发生在近端肾小管细胞。受损细胞的特征是基底襞出现大空泡、不透明颗粒积聚、细胞核向管腔膜迁移、管腔闭塞和/或刷状缘丧失。费希尔344大鼠的形态学损伤比斯普拉格-道利大鼠更广泛。（摘要截短至250字）
