Effects of dietary sodium selenite supplementation on salicylate-induced embryo- and fetotoxicity in the rat.

The effects of dietary supplementation with sodium selenite (3.0 or 4.5 ppm Se) for 8 weeks prior to and throughout gestation on sodium salicylate induced embryo- and fetotoxicity (resorptions, fetal deaths, malformations, fetal weight reduction) have been studied in the rat. Salicylate was administered either as daily intragastric bolus doses of 250 mg/kg on gestation days 6-13 (maternal peak and trough salicylate levels of 222-120 micrograms/ml whole-blood) or via constant rate intravenous infusion of 150 mg/kg/day on the same gestation days via implanted osmotic minipumps (stable average maternal blood salicylate level of 120 micrograms/ml = human antirheumatic concentration). Both gavage and infusion of salicylate resulted in an increase of resorptions and fetal deaths as well as a decrease of fetal body weights. Gavage with salicylate also produced about 50% malformed fetuses. Selenite did not protect against the embryotoxic effects of salicylate administered as intragastric bolus doses. However, selenite was found to significantly increase fetal survival rate in the infusion experiment, although it did not counteract the decrease of fetal body weight. In animals fed selenite only, no negative effects on fetal body development were noted. The protective effect of selenite against salicylate induced embryotoxicity is difficult to explain, since very little is known about the mechanisms of salicylate embryotoxicity and the biological effects of selenium. However, an interaction between selenium, via glutathione peroxidase, and salicylate at the level of prostaglandin synthesis could be possible.