Effects of lithium on growth, maturation, reproduction and gene expression in the nematode Caenorhabditis elegans

J Appl Toxicol. 2015 Sep;35(9):999-1006. doi: 10.1002/jat.3058. Epub 2015 Jan 21.

Abstract

Lithium (Li) has been widely used to treat bipolar disorder, and industrial use of Li has been increasing; thus, environmental pollution and ecological impacts of Li have become a concern. This study was conducted to clarify the potential biological effects of LiCl and Li(2)CO(3) on a nematode, Caenorhabditis elegans as a model system for evaluating soil contaminated with Li. Exposure of C. elegans to LiCl and Li(2)CO(3) decreased growth/maturation and reproduction. The lowest observed effect concentrations for growth, maturation and reproduction were 1250, 313 and 10 000 µm, respectively, for LiCl and 750, 750 and 3000 µm, respectively, for Li(2)CO(3). We also investigated the physiological function of LiCl and LiCO(3) in C. elegans using DNA microarray analysis as an eco-toxicogenomic approach. Among approximately 300 unique genes, including metabolic genes, the exposure to 78 µm LiCl downregulated the expression of 36 cytochrome P450, 16 ABC transporter, 10 glutathione S-transferase, 16 lipid metabolism and two vitellogenin genes. On the other hand, exposure to 375 µm Li(2)CO(3) downregulated the expression of 11 cytochrome P450, 13 ABC transporter, 13 lipid metabolism and one vitellogenin genes. No gene was upregulated by LiCl or Li(2)CO(3). These results suggest that LiCl and Li(2)CO(3) potentially affect the biological and physiological function in C. elegans associated with alteration of the gene expression such as metabolic genes. Our data also provide experimental support for the utility of toxicogenomics by integrating gene expression profiling into a toxicological study of an environmentally important organism such as C. elegans.

Keywords: Caenorhabditis elegans; growth; lithium; maturation; microarray; reproduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / drug effects*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans Proteins / genetics*
  • Environmental Pollutants / toxicity*
  • Gene Expression / drug effects*
  • Lethal Dose 50
  • Lithium / toxicity*
  • Lithium Carbonate / toxicity
  • Lithium Chloride / toxicity
  • Oligonucleotide Array Sequence Analysis
  • Reproduction / drug effects

Substances

  • Caenorhabditis elegans Proteins
  • Environmental Pollutants
  • Lithium Carbonate
  • Lithium
  • Lithium Chloride