Gene/Protein Disease Symptom Drug Enzyme Compound
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Pentavalent vanadium (V5) as Na48VO3 was given i.p. to male Wistar rats at a dose of 5 mumol/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 mumol/kg. Desferal (30 mumol/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 mumol/kg) were 7%, plus 15%, and 0%, respectively. At 100 mumol/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.
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PMID:The effect of chelating agents on vanadium distribution in the rat body and on uptake by human erythrocytes. 692 68