Correlation between prevention of cataract development by disulfiram and fates of selenium in selenite-treated rats.
OBJECTIVE
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.
Ito
Y
Y
School of Pharmacy, Kinki University, Higashi-Osaka, Osaka, Japan.
Cai
H
H
Koizumi
Y
Y
Nakao
M
M
Terao
M
M
D000281:Administration, Intranasal; D000818:Animals; D002386:Cataract / Q000139:chemically induced / Q000517:prevention & control*; D004221:Disulfiram / Q000008:administration & dosage / Q000494:pharmacology*; D004050:Ditiocarb / Q000032:analysis; D004337:Drug Carriers; D005260:Female; D008081:Liposomes; D008297:Male; D016877:Oxidants / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000097:blood / Q000493:pharmacokinetics*; D018038:Sodium Selenite / Q000494:pharmacology*; D014018:Tissue Distribution / Q000187:drug effects
D004337:Drug Carriers; D008081:Liposomes; D016877:Oxidants; D004050:Ditiocarb; D012643:Selenium; D018038:Sodium Selenite; D004221:Disulfiram