Toxicological and cytophysiological aspects of lanthanides action.

Abstract

Lanthanides, also called rare-earth elements, are an interesting group of 15 chemically active, mainly trivalent, f-electronic, silvery-white metals. In fact, lanthanides are not as rare as the name implies, except for promethium, a radioactive artificial element not found in nature. The mean concentrations of lanthanides in the earth's crust are comparable to those of life-important elements like iodine, cobalt and selenium. Many lanthanide compounds show particular magnetic, catalytic and optic properties, and that is why their technical applications are so extensive. Numerous industrial sources enable lanthanides to penetrate into the human body and therefore detailed toxicological studies of these metals are necessary. In the liver, gadolinium selectively inhibits secretion by Kupffer cells and it decreases cytochrome P450 activity in hepatocytes, thereby protecting liver cells against toxic products of xenobiotic biotransformation. Praseodymium ion (Pr3+) produces the same protective effect in liver tissue cultures. Cytophysiological effects of lanthanides appear to result from the similarity of their cationic radii to the size of Ca2+ ions. Trivalent lanthanide ions, especially La3+ and Gd3+, block different calcium channels in human and animal cells. Lanthanides can affect numerous enzymes: Dy3+ and La3+ block Ca2+-ATPase and Mg2+-ATPase, while Eu3+ and Tb3+ inhibit calcineurin. In neurons, lanthanide ions regulate the transport and release of synaptic transmitters and block some membrane receptors, e.g. GABA and glutamate receptors. It is likely that lanthanides significantly and uniquely affect biochemical pathways, thus altering physiological processes in the tissues of humans and animals.

Highly Selective Recovery of Lanthanides by Using a Layered Vanadate with Acid and Radiation Resistance

“…For instance, europium as the representative of lanthanides has relatively long‐lived radioisotopes ( 152 Eu: t 1/2 ≈13.3 years; 154 Eu: t 1/2 ≈8.6 years) that may penetrate into human body and significantly alter normal physiological processes by inhibiting enzymes, regulating synaptic transmitters and blocking membrane receptors . Importantly, Eu 3+ is typically employed as the simulant for long‐lived radiotoxic actinides (An 3+ ) such as Am 3+ for their similar adsorption properties . However, the effective sequestration of actinides and lanthanides (Ln) from complex radioactive wastes, especially the high level liquid waste (HLLW) under strong acidic conditions, remains a serious challenge because of the effects of protonation and retardation of material stability .…”

Molecular neurochemistry of the lanthanides

“…Abbreviations: AChE; acetylocholinoesterase, AMPA; α-amino-3-hydroxy-5-methyl-4isoxazolepropionic acid glutamate receptor, Axud1; cysteine-serine-rich nuclear protein1, Adcy8; calcium-stimulated adenylyl cyclase, Cdd37; cell division 37 homologue, Fos; proto-oncogene AP-1 transcription factor subunit, G; protein G, GLAST; glutamateaspartate transporter GS; glutamine syntethase, KAR; kainate glutamatergic receptor, mGluR; metabotropic glutamate receptor, NERT; norepinephrine transporter, NMDA; N-methyl-D-aspartate glutamatergic receptor, PAG; phosphate activated glutaminase, Slc5a7; solute carrier family 5 member 7 gene, SNARE; soluble NSF attachment protein, TRPVs; vanilloid-type heat-activated ion channels,Ube2v1; ubiquitin-conjugating enzyme e2, VGKC; voltage-gated potassium channel, VGSC; voltage-gated sodium channels including lanthanides may modify channel gating or block ion currents (Elinder & Arhem, 2003). Because of its uniquely strong gating activity, La 3+ is sometimes called a "supercalcium" (Brown, Rathjen, Graham, & Tribe, 1990) and the effects of lanthanides on voltage-gated ion channels including potassium and calcium have been previously reported in diverse cell types (Pałasz & Czekaj, 2000). Trivalent lanthanide cations directly block ion flow through neuronal voltage-gated K + channels (VGKC) with a potency that varies inversely with the ionic radius (Alshuaib & Mathew, 2005;Enyeart, Gomora, & Enyeart, 1998).…”

Small is Smarter: Nano MRI Contrast Agents – Advantages and Recent Achievements

“…[ 46 ] Further in vitro cellular studies suggested that RE 3+ ions may interfere with Ca 2+ channels owing to their comparable radius, thus affecting the physiological processes within the tissues. [ 47,48 ] Nevertheless, the rat studies suggested that Gd 3+ is less toxic than Mn 2+ , [ 49 ] although the latter is also a useful paramagnetic ion for constructing T 1 contrast agents. Until now, most clinical MRI contrast agents are chosen from Gd-chelates due to their low release levels of free Gd 3+ ions and quick renal clearance, although patients with renal disease are subjected to risks of severe complication such as nephrogenic systemic fi brosis.…”