A urinary metabolomics study of a Polish subpopulation environmentally exposed to arsenic

Background: Almost every organ in the human body can be affected by arsenic (As) exposure associated with various industrial processes, as well as with contaminated food, drinking water and polluted air. Much is known about high exposure to inorganic As but there is little data on the metabolic changes connected to a low exposure e.g. in people living in smelter areas.

Objectives: The objectives of the study were: (1) characterise urinary concentration of total arsenic (AsT) in Polish inhabitants of the vicinity of a copper smelter area, (2) speciation analysis of various forms of arsenic in girls (GL), boys (BL), women (WL) and men (ML) with a slightly elevated AsT concentration and age/sex matched groups with a substantially higher AsT concentration, (GH, BH, WH and MH - respectively), (3) comparison of metabolomics profiles of urine between the age/sex matched people with low and high AsT concentrations.

Methods: Urine samples were analysed for total arsenic and its chemical forms (As^III; As^V, methylarsonic acid, dimethylarsinic acid, arsenobetaine) using HPLC-ICP-MS. Untargeted metabolomics analysis of the urine samples was performed using UPLC system connected to Q-TOF-MS equipped with an electrospray source. The XCMS Online program was applied for feature detection, retention time correction, alignment, statistics, annotation and identification. Potentially identified compounds were fragmented and resulting spectra were compared to the spectra in the Human Metabolome Database.

Results: Urine concentration of AsT was, as follows: GL 16.40 ± 0.83; GH 115.23 ± 50.52; BL 16.48 ± 0.83; BH 95.00 ± 50.03; WL 16.93 ± 1.21; WH 170.13 ± 96.47; ML 16.91 ± 1.20; MH 151.71 ± 84.31 μg/l and percentage of arsenobetaine in AsT was, as follows: GL 65.5 ± 13.8%, GH 87.2 ± 4.7%, BL 59.8 ± 12.5%, BH 90.5 ± 2.4%, WL 50.8 ± 14.1%, WH 90.4 ± 3.5%, ML 53.3 ± 10.0%, MH 74.6 ± 20.2%. In the people with low and high AsT concentrations there were significant differences in the intensity of signal (is.) from numerous compounds being metabolites of neurotransmitters, nicotine and hormones transformation (serotonin in the girls and women; catecholamines in the girls, boys and women; mineralocorticoids and glucocorticoids in the boys, androgens in the women and men and nicotine in the boys, women and men). These changes might have been associated with higher is. from metabolites of leucine, tryptophan, purine degradation (in the GH, WH), urea cycle (in the WH and MH), glycolysis (in the WH) and with lower is. from metabolites of tricarboxylic acid cycle (in the BH) in comparison with low AsT matched groups. In the MH vs. ML higher is. from metabolite of lipid peroxidation (4-hydroxy-2-nonenal) was observed. Additionally, the presence of significant differences was reported in is. from food components metabolites, which might have modulated the negative effects of As (vitamin C in the girls, boys and men, vitamin B₆ in the girls, boys and women as well as phenolic compounds in the boys and girls). We hypothesize that the observed higher is. from metabolites of sulphate (in MH) and glucoronate degradation (in BH, WH and MH) than in the matched low AsT groups may be related to the impaired glucuronidation and sulfonation and higher is. from catecholamines, nicotine and hormones.

Conclusion: Our results indicated that even a low exposure to As is associated with metabolic changes and that urine metabolomics studies could be a good tool to reflect their wide spectrum connected to specific environmental exposure to As, e.g. in smelter areas.