PREVENTION BY TIRON (SODIUM 4,5-DIHYDROXYBENZENE-1,3-DISULFONATE) OF VANADATE-INDUCED DEVELOPMENTAL TOXICITY IN MICE

Vanadate is embryotoxic and fetotoxic in golden hamsters, mice and rat s. Tiron (sodium 4,5-dihydroxybenzene-1,3-disulfonate), a chelating ag ent widely used in analytical chemistry, is an effective antidote in t he treatment of oral or parenteral vanadate poisoning. The present stu dy evaluated the effect of administration of Tiron on sodium metavanad ate (NaVO3)-induced developmental toxicity in mice. NaVO3 (25 mg/kg, i .p.) was injected on day 12 of gestation, whereas Tiron was injected s ubcutaneously at 0, 24, 48, and 72 hr after NaVO3 administration. Tiro n effectiveness was assessed at dosage levels of 0, 250, 500, and 1,00 0 mg/kg. Cesarean sections were performed on gestation day 18. All liv e fetuses were examined for external, internal, and skeletal malformat ions and variations. Amelioration by Tiron of NaVO3 developmental toxi city was evidenced by a significant decrease in the number of resorbed fetuses, an increase in the mean fetal weight, and a reduction in the incidence of the skeletal variations caused by NaVO3. According to th ese results, Tiron offers encouragement with regard to its therapeutic potential for pregnant women exposed to vanadate. However, further in vestigations, including the effect of increasing the time interval bet ween acute vanadate exposure and initiation of Tiron therapy, are requ ired. (C) 1993 Wiley-Liss, Inc.