A systems toxicology approach to compare the heavy metal mixtures (Pb, As, MeHg) impact in neurodegenerative diseases.

Conventional toxicological risk assessment methods mainly working on single chemicals that fail to adequately address the simultaneous exposure and their potential toxicity in humans. We herein investigated the toxic heavy metals lead (Pb), arsenic (As), and methylmercury (MeHg) and their binary mixtures role in neurodegenerative diseases. To characterize the toxicity of metal mixtures at the molecular level, we established a non-animal omics-based organ relevant cell model system. The obtained experimental data was refined by using the statistical and downstream functional analysis. The protein expression information substantiates the previous findings of single metal (Pb, As, and MeHg) induced alterations to mitochondrial dysfunction, oxidative stress, mRNA splicing, and ubiquitin system dysfunction relation to neurodegenerative diseases. The functional downstream analysis of single and binary mixtures protein data is presented in a comparative manner. The heavy metals mixtures' outcome showed significant differences in the protein expression compared to single metals that indicate metal mixtures exposure is more hazardous than single metal exposure. These results suggest that more comprehensive strategies are needed to improve the mixtures risk assessment in the future.