Natural variations of lithium isotopes in a mammalian model

作者：Balter Vincent^*; Vigier Nathalie

来源：Metallomics, 2014, 6(3): 582-586.

DOI：10.1039/c3mt00295k

Despite lithium%26apos;s extensive clinical applications, the cellular and molecular basis for the therapeutic effects remains to be elucidated. The large difference in mass between the two lithium isotopes (Li-6 and Li-7) has prompted biochemists to explore the metabolism of Li by using pure 6Li and 7Li labeled drugs. However, experiments were carried out at very high Li concentrations, which did not reflect natural conditions. In the present study, we consider, for the first time, the natural variations of the Li-7/Li-6 ratio in the organs and body fluids of an animal model, sheep. Each organ seems to be characterized by a specific Li isotope composition. So far, the range of the 7Li/6Li ratio in the sheep body, expressed as delta permil variations relative to the L-SVEC standard (delta Li-7), is about 40 parts per thousand, between muscles (similar to 40 parts per thousand) and kidney (similar to 0 parts per thousand). Relative to a dietary delta Li-7 value of similar to +17 parts per thousand, serum, red blood cells, muscle, liver, brain and kidney have a Li-7 enrichment of -12 parts per thousand, -14 parts per thousand, +22 parts per thousand, +5 parts per thousand, -3 parts per thousand and -15 parts per thousand, respectively. The Li isotope composition is likely to be fractionated during intestinal absorption, with a greater absorption of Li-6 relative to Li-7. According to previous conclusions obtained with Li-6 and Li-7 labeled chemicals, Li-6 appears to diffuse into erythrocytes faster than does Li-7. However, this does not hold for myocytes and hepatocytes, because these two tissues have a higher delta Li-7 level than serum. Purely diffusive isotopic fractionation would leave all organs Li-7-depleted relative to the serum, which is not the case, suggesting that active, molecule-specific, isotopic fractionation occurs in the body. Our preliminary results suggest that natural Li isotope variations can shed light on its regulation in the body, being active or passive.

• 出版日期2014