Fujimura A, Ohashi K, Ebihara A
Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
Jpn J Pharmacol. 1991 Dec;57(4):565-9. doi: 10.1254/jjp.57.565.
The present study was undertaken to examine whether urinary excretions of prostaglandins increase by repeated administration of a non-toxic dose of lithium. Our previous study demonstrated that 2 mEq/kg/day of lithium chloride (LiCl) is not a toxic dose; and therefore, this dose of LiCl in 1 ml vehicle (5% glucose solution) or 1 ml of vehicle alone was injected intraperitoneally for 7 days into Wistar rats. On day 7, 3% body weight of 1% NaCl solution was given orally; and urine for the determination of PGE2 and 6-keto-PGF1 alpha, a metabolite of PGI2, was collected for 6 hr after dosage. Thereafter, blood samples for measuring plasma renin activity (PRA) were obtained. The urinary amounts of PGE2 and 6-keto-PGF1 alpha in the Li-treated rats were significantly greater than those in the control animals. The values of PRA did not significantly differ between the two groups of rats. These findings indicate that the production of prostaglandins, including those of PGE2 and PGI2, are enhanced during repeated administration of a non-toxic dose of lithium. The enhanced production of prostaglandins might not be mediated through the activated renin-angiotensin system.
本研究旨在探讨重复给予无毒剂量的锂后,前列腺素的尿排泄量是否会增加。我们之前的研究表明,2 mEq/kg/天的氯化锂(LiCl)并非有毒剂量;因此,将该剂量的LiCl溶于1 ml载体(5%葡萄糖溶液)或仅用1 ml载体腹腔注射到Wistar大鼠体内,持续7天。在第7天,口服给予体重3%的1% NaCl溶液;给药后6小时收集尿液,用于测定PGE2和6-酮-PGF1α(PGI2的一种代谢产物)。此后,采集血样以测量血浆肾素活性(PRA)。锂处理组大鼠的PGE2和6-酮-PGF1α尿排泄量显著高于对照组动物。两组大鼠的PRA值无显著差异。这些发现表明,在重复给予无毒剂量的锂期间,包括PGE2和PGI2在内的前列腺素生成增加。前列腺素生成的增加可能不是通过激活肾素-血管紧张素系统介导的。