Prevention by Tiron (sodium 4,5‐dihydroxybenzene‐1,3‐disulfonate) of vanadate‐induced developmental toxicity in mice

Abstract

Vanadate is embryotoxic and fetotoxic in golden hamsters, mice and rats. Tiron (sodium 4,5-dihydroxybenzene-1,3-disulfonate), a chelating agent widely used in analytical chemistry, is an effective antidote in the treatment of oral or parenteral vanadate poisoning. The present study evaluated the effect of administration of Tiron on sodium metavanadate (NaVO3)-induced developmental toxicity in mice. NaVO3 (25 mg/kg, i.p.) was injected on day 12 of gestation, whereas Tiron was injected subcutaneously at 0, 24, 48, and 72 hr after NaVO3 administration. Tiron effectiveness was assessed at dosage levels of 0, 250, 500, and 1,000 mg/kg. Cesarean sections were performed on gestation day 18. All live fetuses were examined for external, internal, and skeletal malformations and variations. Amelioration by Tiron of NaVO3 developmental toxicity 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 these results, Tiron offers encouragement with regard to its therapeutic potential for pregnant women exposed to vanadate. However, further investigations, including the effect of increasing the time interval between acute vanadate exposure and initiation of Tiron therapy, are required.

Insulin-Like Effects on Liver Golgi Membrane Preparations of Bis(Oxalato)Oxovanadate(IV) Complex Ion, a New Vanadate Compound

“…Vanadium action, as an insulin-like drug widely described by many investigators (15,6,7,8,9,12,13), inspired us to use it in our experiments. Preliminary results of other studies showed biological activity of both forms of vanadium (vanadyl or vanadate) but recent work showed rather the action of vanadyl, and postulating that vanadate is reduced into it within cells (15,21,17,18). The vanadium-oxalate complex (similar to commonly used vanadium derivatives) was reluctantly drunk by the rats and caused diminished fluid consumption.…”

“…Some drugs were used usually together with vanadium, lowering its toxicity, especially in animals with streptozotocin (SZ) induced diabetes: the most 0.3%-0.8% NaCI (14,19). The vitamin E, aforesaid lazaroid, V-83836e (20), Tiron (4,5-dihydroxybenzene-1 ,3-disulfonate) (21), deferoxyamine, EDTA, ksylenol orange, base fenantroline (22) were also applied.…”

Tiron Inhibits UVB-Induced AP-1 Binding Sites Transcriptional Activation on MMP-1 and MMP-3 Promoters by MAPK Signaling Pathway in Human Dermal Fibroblasts

“…Tiron, 4, 5-dihydroxy-1, 3-benzene disulfonic acid, with the water-soluble and cell permeable characteristic, is an effective antioxidant, that can remove all kinds of harmful free radicals [ 11 ]. For example, it can reverse the reactive oxygen species (ROS)-induced cell apoptosis, or act as a nontoxic chelating agent to alleviate the acute toxic metal overload [ 12 ]. Tiron has been reported to be able to inhibit apoptosis in human lung cancer cells induced by bortezomib [ 13 ].…”

Novel therapeutic strategies for the treatment of Type 2 diabetes

“…The association of vanadate with Tiron, a chelating agent, has been shown to be effective in preventing vanadate poisoning, without altering its glucose lowering ability. 96 The attempts to minimize the toxic effects associated with vanadate treatment are not conclusive. The resolution of these fundamental issues is essential prior to making vanadate a valuable option in the treatment of hyperglycemia.…”