RESUMO
Low molecular weight and high molecular weight metal ion binders present in blood plasma are shortly described. The binding of vanadium and ruthenium complexes by these components has received much attention, namely their interactions with human serum albumin and transferrin, and these studies are critically reviewed. The influence of the protein binding on the bioavailability of the prospective drugs, namely on the transport by blood plasma and uptake by cells is also discussed. It is concluded that vanadium compounds are mainly transported in blood by transferrin, but that no study has properly addressed the influence of albumin and transferrin in the vanadium uptake by cells. Ruthenium complexes bind strongly to HSA, most likely at the level of His residues, leading to the formation of stable adducts. If the kinetics of binding to this protein is fast enough, probably they are mainly transported by this serum protein. Nevertheless, at least for a few Ru(III)-complexes, hTf seems to play an active role in the uptake of ruthenium, while HSA may provide selectivity and higher activity for the compounds due to an enhanced permeability effect.
Assuntos
Proteínas Sanguíneas/metabolismo , Complexos de Coordenação/sangue , Compostos de Rutênio/sangue , Compostos de Vanádio/sangue , Transporte Biológico , Ensaios Clínicos como Assunto , Complexos de Coordenação/química , Complexos de Coordenação/metabolismo , Complexos de Coordenação/uso terapêutico , Humanos , Peso Molecular , Ligação Proteica , Rutênio/sangue , Rutênio/química , Rutênio/metabolismo , Compostos de Rutênio/química , Compostos de Rutênio/metabolismo , Compostos de Rutênio/uso terapêutico , Radioisótopos de Rutênio/sangue , Radioisótopos de Rutênio/química , Radioisótopos de Rutênio/metabolismo , Radioisótopos de Rutênio/uso terapêutico , Albumina Sérica/metabolismo , Análise Espectral , Transferrina/metabolismo , Vanádio/sangue , Vanádio/química , Vanádio/metabolismo , Compostos de Vanádio/química , Compostos de Vanádio/metabolismo , Compostos de Vanádio/uso terapêuticoRESUMO
The interest in the biokinetics of ruthenium and zirconium in humans is justified by the potential radiological risk represented by their radionuclides. Only a few data related to the biokinetics of ruthenium and zirconium in humans are available and, accordingly, the biokinetic models currently recommended by the ICRP for these elements are mainly based on data from animal experiments. The use of stable isotopes as tracers, coupled with a proper analytical technique (nuclear activation analysis with protons) for their determination in biological samples, represents an ethically acceptable methodology for biokinetic investigations, being free from any radiation risk for the volunteer subjects. In this work, the results obtained in eight biokinetic investigations for ruthenium, conducted on a total of three healthy volunteers, and six for zirconium, performed on a total of three subjects, are presented and compared to the predictions of the ICRP models.