November 29, 2012

The Neural Toxicity Of Lanthanides: An Update And Interpretations

Lanthanides comprise a unique and dominant resource of China. The increase in contact for populations through lanthanide mining and the wide applications for industry, agriculture, and medicine have raised great public concern regarding the metal toxicity of lanthanides, particularly on the issue of whether lanthanides are toxic to the human nervous system.

In the past decade, major progresses have been made toward elucidating the mechanisms of the biological actions of lanthanides. A recently published review by researchers at Peking University [Xia et al., Sci. China Chem. 2012;42(9):1308] provided us with a update on current research results and their implications for the neurotoxicity of lanthanides.

At the end of the last century, several investigations were conducted on the intelligence quotient (IQ) and the physical growth and development of children in the mining area. The reports indicated that children with environmental exposure to lanthanides showed certain changes in their IQ, vital capacity, blood pressure, immunoglobulins, and post-exercise heart rate, suggesting possible adverse effects of lanthanides on the neural system. Subsequently, Chinese scientists initiated a series of studies on the neurological and toxicological effects of lanthanides.

This review summarized the important results of the previous studies, including the permeation of lanthanides across the brain—blood barrier, the responses of neural systems to lanthanide exposure, and the actions and molecular mechanisms of lanthanides on neural cells. The authors also discussed the implications of the current results for the issue of whether lanthanides are toxic toward neural systems.

It was confirmed that lanthanide ions cannot pass through an intact and fully functional blood—brain barrier. However, blood—brain barrier hypoplasia and some injuries caused by environmental and/or pathological factors make this barrier permeable to lanthanides, thereby altering the neural functions. Most studies indicated that high doses and/or chronic exposure to lanthanides would damage the neural system, especially for animals during pregnancy and lactation periods, while a small portion of studies indicated that lanthanides exhibited neuroprotective effects.

Further investigations into the molecular mechanisms of the neurological effects of lanthanides indicated that neuronal cells are affected by lanthanide ions. Treatment with lanthanides could modify neural signaling, cause oxidative and related stresses, and decrease neuronal cell viability at high doses. However, astrocytes tolerate lanthanide ions and prevent lanthanide-induced damage to neuronal cells by secreting brain-derived neurotrophic factor. The toxicological behaviors are thus very complicated and the effects depend on a variety of factors.

In the discussion, the authors indicated that the current results are not sufficient to bring about conclusive answers to the questions regarding lanthanide neurotoxicity. Consequently, further studies are warranted. Nonetheless, attention must be paid to the potential neurotoxicity of lanthanides in certain populations, including patients taking lanthanide agents (e.g. lanthanum carbonate drugs and gadolinium-containing contrast agents) and children under lanthanide exposure.


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