Lanthanum and cerium disrupt similar biological pathways and interact synergistically in Triticum aestivum as revealed by metabolomic profiling and quantitative modeling

Highlights: • La/Ce exposure induced significant metabolic change in a dose-dependent manner. • La and Ce possessed similar mode of action at the metabolic level. • La/Ce exposure caused oxidative stress, energy disturbance, DNA and membrane damage. • Synergistic interaction of La-Ce mixture at metabolic level was quantified by MELI. • Interaction pattern at metabolic-level is consistent with that at the individual level. The industrial and agricultural applications of rare earth elements (REEs) lead to considerable REE emissions into environment. Yet, little is known about the molecular-level effects and interactions of REEs in terrestrial plants. Herein, the individual and joint effects of La and Ce in Triticum aestivum were investigated using mass spectrometry-based metabolomics. Metabolic effect level index (MELI) was utilized as a readable endpoint for quantifying mixture interactions. Exposure to single La/Ce at environmentally relevant levels induced significant dose-dependent metabolic changes. The highly overlap of differential metabolites and perturbed pathways of La and Ce suggested their similar mode of action. Exposure to La-Ce mixtures did not induce additional metabolic pathway perturbation. Specifically, metabolism of amino sugar and nucleotide sugar, starch and sucrose, fructose and mannose, glycerophospholipid and purine were disrupted for both single and binary exposures. These results, together with physiological indicators, point to REE-induced oxidative stress, energy expenditure, DNA damage and membrane disturbance. The MELI calculations showed that La and Ce interacted synergistically at the overall metabolic level, which could be causally linked to synergistic interaction at the individual level (root elongation). This work proved metabolomics could be an important and effective strategy for interpreting toxicity and interactions of REE mixtures.