[In vitro dissolution of metallic oxides in human plasma and binding of metals to plasma proteins--effect of chelators].

Abstract

The solubility in biological liquids of oxides is one of the factors which determinate the speed of penetration into the blood stream of toxic agents contained in solid particles inside pulmonary alveoli. This solubility was studied in vitro for the six following metal oxides: Cd, Cr, Fe, Mn, Pb, Zn, by holding particle oxides in suspension into human plasma at 37 degrees C, during variable time. The experimentation was realized on particles which belong to two categories which sizes are 0.45-2 and 2-5 mu. The evolution of metal oxide dissolved level according to time have enabled exponential relation parameters to be calculated. These parameters translate the particle oxide dissolution into plasma and have permitted to classify metal oxide in decreasing solubility order: Cd, Zn, PbO, Fe2O3, Fe3O4, Mn, PbO2, Pb3O4 and Cr2O3. The second part of the experimentation is about dissolved metal distribution between the different protein fractions. Dissolved metal is distributed between diffusible metal (lower than 10 per cent) and metal binding proteins chiefly in albumin except for Fe which is bound to transferrin. Chelating agents into plasma reduce the proportion of metals bound to proteins. EDTA Ca is energetic on all metals mainly on Lead, Cadmium, and Zinc. N-acetyl-DL penicillamin is less energetic. Meso 2,3 dimercapto succinic acid, and 2,3 dimercapto-1-propan sulfonic acid have an effect only on Lead but in a very light way. Desferrioxamin release a great proportion of Iron bound to proteins. These results, obtained in vitro, are similar to those from animal experimentation or those observed in human therapeutic.