The effect of chelating agents on vanadium distribution in the rat body and on uptake by human erythrocytes

Abstract

Pentavalent vanadium (V⁵) as Na⁴⁸VO₃ was given i.p. to male Wistar rats at a dose of 5 μmol/kg in order to study its organ distribution pattern. Two days after injection, kidneys reached a V level of about 28 nmol/g wet weight, followed in decreasing order by spleen, liver, bone, blood plasma, testis, lung, erythrocytes and brain in control rats. A similar distribution pattern was seen after injection of tetravalent vanadium (V⁴) given as ⁴⁸VOSO₄. Two chelators, desferrioxamine B (Desferal) or Ca-Na₃-diethylene triamine pentaacetic acid (DTPA), were given i.p. 24 h after the vanadium injections to different groups of rats at two dosage levels, 30 and 100 μmol/kg. Desferal (30 μmol/kg) reduced the vanadium content of the kidney by 17%, of the liver by 0%, and of the lung by 7%. The corresponding figures for the effect of DTPA (30 μmol/kg) were 7%, plus 15%, and 0%, respectively. At 100 μmol/kg, Desferal reduced the same organ levels by 20%, 26%, and 25%, respectively, and DTPA by 9%, 18%, and 25%, respectively. Both chelators raised faecal excretion at the low level, and both urinary and faecal excretion at the high level. Spleen and bone seemed to bind vanadium to a higher degree than the other organs under examination.

Human erythrocytes, when incubated with ⁴⁸VOSO₄ (V⁴) or Na⁴⁸VO₃ (V⁵), were found to accumulate nearly the double amount of V⁵ as compared to V⁴. Glutathione (GSH) which is the main reducing substance within the erythrocytes, reduced the uptake of V⁵ to the V⁴ level when incubated together with GSH before addition to the cell suspension. Pretreating the erythrocytes with diethyl-maleate (DEM) which blocks the reducing SH groups of intracellular GSH, also reduced the uptake of V⁵. This may indicate a GSH dependent reduction of V⁵ to V⁴ within the erythrocytes. Four chelators, among them Desferal and DTPA, were found to reduce the cellbound amount of vanadium, either by extracting vanadium as V⁴, or by inhibiting uptake by the red blood cells.