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Correlation between prevention of cataract development by disulfiram and fates of selenium in selenite-treated rats
Insights
Disulfiram (DSF) eye drops prevented selenite-induced cataracts in rat pups by reducing ocular selenium levels. Disulfiram and its metabolite diethyldithiocarbamate (DDC) may also act as antioxidants against cataract formation.
Area of Science:
- Ophthalmology
- Pharmacology
- Toxicology
Background:
- Cataracts can be induced in young rats by selenite injection.
- Disulfiram (DSF) is a drug with potential pharmacological effects.
- Understanding the mechanism of selenite-induced toxicity is crucial for developing treatments.
Purpose of the Study:
- To investigate the novel pharmacological effect of disulfiram (DSF) in preventing selenite-induced cataracts in rat pups.
- To explore the underlying reactive mechanisms of DSF in this context.
Main Methods:
- Selenite-induced cataracts in 13-day-old Wistar rats.
- Intraocular administration of DSF-liposomes and nasal administration of DSF suspensions.
- Monitoring lens opacification using slit lamp and EAS-1000.
- Quantification of selenium content in organs and plasma via fluorimetry and HPLC.
- Measurement of diethyldithiocarbamate (DDC) plasma concentrations.
Main Results:
- DSF-liposomes effectively prevented cataract formation in rat pups.
- DSF treatment significantly reduced selenium levels in plasma and eyes.
- Older rats (30 days) showed resistance to selenite-induced cataracts, with lower baseline selenium levels.
- DSF metabolite DDC levels decreased in plasma post-selenite injection; nasal DSF decreased plasma selenium.
Conclusions:
- Ocular instillation of DSF-liposomes prevents selenite-induced cataracts in rat pups.
- The inhibitory mechanism likely involves decreased ocular selenium levels.
- DSF and its metabolite DDC may possess antioxidant properties, counteracting selenite-induced oxidative stress in the lens.
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.