Dorian C, Cambar J
Pathol Biol (Paris). 1986 Jun;34(5 Pt 2):587-90.
We have studied the circadian variations in the nephrotoxicity of a single dose of a recently developed aminoglycoside, amikacin, in rats. Male rats placed in cages providing constant thermal conditions and lighted from 08:00 to 20:00 h were given a single intraperitoneal injection of 1.2 g/kg amikacin at different times of the 24 hour cycle (08:00, 14:00, 20:00 or 02:00). The study was carried out in October/November. Several parameters were monitored, including urinary excretion of gamma-glutamyl transferase, an enzyme found in the brush border of proximal tubule cells. The increase in urinary excretion of gamma-glutamyl transferase (expressed as a percentage) was found to vary according to the time of administration of amikacin. The highest GGT excretion occurred following administration of amikacin at 20:00 (484% +/- 62.75) and the lowest excretion, similar to that observed in controls, was found following administration at 14:00 (127% +/- 16.85). Thus, it seems that circadian variations in amikacin nephrotoxicity exist in rats. In a previous study we had found circadian variations in acute amikacin nephrotoxicity in mice. A thorough knowledge of these phenomena would improve our use of antibiotics in human clinical practice.
我们研究了单次剂量的一种新开发的氨基糖苷类药物阿米卡星对大鼠肾毒性的昼夜变化。将雄性大鼠置于提供恒定热条件且在08:00至20:00光照的笼子中，在24小时周期的不同时间（08:00、14:00、20:00或02:00）给它们单次腹腔注射1.2 g/kg阿米卡星。该研究在10月/11月进行。监测了几个参数，包括γ-谷氨酰转移酶的尿排泄，γ-谷氨酰转移酶是一种存在于近端小管细胞刷状缘的酶。发现γ-谷氨酰转移酶尿排泄的增加（以百分比表示）根据阿米卡星的给药时间而变化。在20:00给予阿米卡星后γ-谷氨酰转移酶排泄最高（484%±62.75），而在14:00给药后排泄最低，与对照组观察到的相似（127%±16.85）。因此，似乎大鼠中存在阿米卡星肾毒性的昼夜变化。在先前的一项研究中，我们发现小鼠急性阿米卡星肾毒性存在昼夜变化。对这些现象的深入了解将改善我们在人类临床实践中对抗生素的使用。
