Natural variations of lithium isotopes in a mammalian model

Abstract

Despite lithium'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 (6Li and 7Li) 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 7Li/6Li 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 δ permil variations relative to the L-SVEC standard (δ7Li), is about 40‰, between muscles (∼40‰) and kidney (∼0‰). Relative to a dietary δ7Li value of ∼+17‰, serum, red blood cells, muscle, liver, brain and kidney have a 7Li enrichment of -12‰, -14‰, +22‰, +5‰, -3‰ and -15‰, respectively. The Li isotope composition is likely to be fractionated during intestinal absorption, with a greater absorption of 6Li relative to 7Li. According to previous conclusions obtained with 6Li and 7Li labeled chemicals, 6Li appears to diffuse into erythrocytes faster than does 7Li. However, this does not hold for myocytes and hepatocytes, because these two tissues have a higher δ7Li level than serum. Purely diffusive isotopic fractionation would leave all organs 7Li-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. © 2014 The Royal Society of Chemistry.