title: An in silico toxicogenomics approach for inferring potential diseases associated with maleic acid.
abstract: Maleic acid is a multi-functional chemical widely applied in the manufacturing of polymer products including food packaging. However, the contamination of maleic acid in modified starch has raised the concerns about the effects of chronic exposure to maleic acid on human health. This study proposed a novel toxicogenomics approach for inferring functions, pathways and diseases potentially affected by maleic acid on humans by using known interactions between maleic acid and proteins. Neuronal signal transmission and cell metabolism were identified to be most influenced by maleic acid in this study. The top disease categories inferred to be associated with maleic acid were mental disorder, nervous system diseases, cardiovascular diseases, and cancers. The results from the in silico analysis showed that maleic acid could penetrate the blood-brain barrier to affect the nervous system. Several functions and pathways were further analyzed and identified to give insights into the mechanisms of maleic acid-associated diseases. The toxicogenomics approach may offer both a better understanding of the potential risks of maleic-acid exposure to humans and a direction for future toxicological investigation.
authors.affiliation: School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; Ph.D. Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: yclin@kmu.edu.tw.
authors.forename: Ying-Chi
authors.initials: YC
authors.lastname: Lin
authors.affiliation: School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; Ph.D. Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Environmental Engineering, National Sun Yat-sen University, Kaohsiung, Taiwan; National Environmental Health Research Center, National Health Research Institutes, Miaoli County, Taiwan. Electronic address: chiachiwang@kmu.edu.tw.
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Wang
authors.affiliation: School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; Ph.D. Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; National Environmental Health Research Center, National Health Research Institutes, Miaoli County, Taiwan. Electronic address: cwtung@kmu.edu.tw.
authors.forename: Chun-Wei
authors.initials: CW
authors.lastname: Tung
mesh_terms: D001812:Blood-Brain Barrier / Q000187:drug effects; D003198:Computer Simulation; D062126:Databases, Chemical; D005506:Food Contamination / Q000032:analysis; D018857:Food Packaging; D059022:Food Safety; D063990:Gene Ontology; D006801:Humans; D008298:Maleates / Q000493:pharmacokinetics / Q000633:toxicity*; D060066:Protein Interaction Maps / Q000187:drug effects; D011506:Proteins / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013213:Starch / Q000633:toxicity; D043922:Toxicogenetics
chemical_list: D008298:Maleates; D011506:Proteins; D013213:Starch; C030272:maleic acid
keywords: Diseases; In silico analysis; Maleic acid; Toxicogenomics