Correlation between prevention of cataract development by disulfiram and fates of selenium in selenite-treated rats.
Correlation between prevention of cataract development by disulfiram and fates of selenium in selenite-treated rats.
复制标题
在亚硒酸盐治疗的大鼠中，双硫仑预防白内障发展与硒的命运之间的相关性。
DOI：
10.1076/ceyr.18.4.292.5356
复制
发表时间：
1999
影响因子：
2
通讯作者：
M. Terao
中科院分区：
文献类型：
--
作者：
Y. Ito;H. Cai;Y. Koizumi;M. Nakao;M. Terao
目的
我们发现双硫仑（DSF）对亚硒酸盐注射诱发的白内障幼鼠有新的药理作用。本文讨论了可能的反应机制。
方法
本研究使用 13 天和 30 天的 Wistar 雄性和雌性大鼠以及 7 周龄的雄性大鼠。通过向 13 日龄大鼠注射亚硒酸盐（19 微摩尔/千克，皮下注射）诱导白内障。通过使用配备有眼前段分析系统（EAS-1000，Nidek）的裂隙灯来监测晶状体浑浊度。采用荧光法检测大鼠器官中的硒含量。采用反相蒸发法制备含DSF的脂质体（DSF-脂质体）。将 5 微升 DSF 脂质体滴入幼鼠双眼，每天 4 次。通过鼻插管向成年大鼠施用 DSF 混悬液（100 mg/kg）。采用HPLC法测定双硫仑代谢物二乙基二硫代氨基甲酸酯(DDC)的血浆浓度变化。
结果
使用 DSF 脂质体进行眼内治疗可预防注射亚硒酸钠的幼鼠白内障的发生。 DSF 治疗还显着降低了治疗后 1 小时血浆中和治疗 96 小时眼中的硒含量。灌输DSF脂质体或不含DSF脂质体的13日龄大鼠肝脏和肾脏中的硒含量没有观察到显着差异。相同剂量的亚硒酸盐(19μmol/kg)对30日龄大鼠不能诱发白内障，且老年大鼠的肝脏、肾脏，尤其是眼睛的硒含量低于13日龄大鼠。二乙基二硫代氨基甲酸酯 (DDC) 是 DSF 的一种活性代谢物，皮下注射亚硒酸钠后血浆中的含量减少。通过鼻内给予DSF悬浮液，血浆中的硒浓度降低。
结论
将 DSF 脂质体滴入皮下注射亚硒酸钠诱导白内障的幼鼠眼睛中，可防止白内障的形成。抑制机制可能是由于 DSF 治疗后眼睛中的硒水平降低所致。另一方面，众所周知，白内障可能是由亚硒酸盐诱导的晶状体氧化应激引起的，DSF和DDC可能起到抗氧化剂的作用。
PURPOSE
We found a new pharmacological effect of disulfiram (DSF) against rat pups with cataract induced by selenite injection. The possible reactive mechanism is discussed in this present paper.
METHODS
Wistar male and female rats aged 13 and 30 days, and male rats aged 7 weeks were used this present study. Cataract was induced by injection of selenite (19 micromol/kg, s.c.) to 13-day old rats. The lens opacification was monitored by using the slit lamp equipped with an anterior eye segment analysis system (EAS-1000, Nidek). The selenium contents in rat organs were detected fluorimetrically. Liposomes containing DSF (DSF-liposomes) were prepared by the reverse-phase evaporation method. Rat pups were instilled 5 microl of DSF-liposomes into both eyes 4 times per day. Adult rats were administered with DSF suspensions (100 mg/kg) by nasal cannulation. The changes of plasma concentration of diethyldithiocarbamate (DDC), which was a metabolite of disulfiram, were determined by HPLC method.
RESULTS
Intraocular treatment with DSF-liposomes prevented the onset of cataract development in rat pups injected with sodium selenite. Treatment with DSF also significantly reduced the selenium contents in plasma at 1 h post-treatment and in the eye at 96 h post-treatment. No significant differences of selenium content in liver and kidney were observed in 13-day old rats instilled with DSF-liposomes or DSF free liposomes. Cataract could not be induced in the 30-days-old rats with the same dose of selenite (19 micromol/kg) and the liver, kidney, and especially eye of the older rats had lower levels of selenium than 13-day old rats. Diethyldithiocarbamate (DDC), an active metabolite of DSF, was decreased in the plasma following a subcutaneous injection of sodium selenite. The selenium concentration in the plasma was decreased by the intranasal administration of DSF suspensions.
CONCLUSIONS
Instillation of DSF-liposomes into the eyes of rat pups given a subcutaneous injection of sodium selenite to induce cataracts prevented the formation of cataracts. The mechanism of inhibition may have resulted from a decreased level of selenium in the eyes following the treatment with DSF. On the other hand, as it is known that the cataracts may result from selenite-induced oxidative stress in the lens, DSF and DDC may react as anti-oxidants.