Abstract
Heavy metals exist ubiquitously in the living environment, and are very stable to accumulate in the food chain. Human are exposed to heavy metals by means of food, air and water. In recent years, there happened food safety scandals in Taiwan. The kitchen waste or gutter oil were recovered and refined by unscrupulous vendors, and sold to food stalls and restaurants. Diner-out has more chances to expose the heavy metals remained in the inferior oil after repetitive refining. Arsenic (As), cadmium (Cd) and lead (Pb) have been known as endocrine disrupting chemicals, which can bind with nuclear receptors to influence normal biological functions, and potentially induce inflammatory response to secret C-reactive protein (CRP) as a result of cardiovascular disease (CVD). In the decade, growth rate of CVD mortality of young adults has obviously increased. Therefore, this study aimed to investigate the correlation of urinary concentrations of heavy metals between physiological index and lifestyle, and whether heavy metals exposure affected gene expression of nuclear receptors genes to give rise to inflammatory response and trigger CRP secretion in dining-out young adults potentially for CVD development. One hundred dining-out young adults aged 18-45 were recruited in this study, and informed consent to provide their urine and blood samples and questionnaire information. Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the urinary concentrations of As, Cd and Pb. Quantitative real time polymerase chain reaction was used to detect the gene expressions of nuclear receptors genes, including hormone-related receptors (androgen receptor (AR), estrogen receptor α (ESR1), ESR2, G protein-coupled estrogen receptor 1 (GPER1)), lipometabolism-related receptors (peroxisome proliferator activated receptor α (PPARA), PPARG), and xenobiotic detoxification-related receptors (NR1I2 and AHR)). Plasma CRP was determined using enzyme-linked immunosorbent assay. This study found that there were correlations between As with Cd or Pb, and the young adults with higher frequency of cosmetics usage, seafood or fried food consumption had significant higher urinary arsenic levels. Study subjects who burned incense or consumed canned food more frequently were observed to have higher urinary Cd levels. Drinking water from water dispenser presented higher urinary Pb levels. Furthermore, urinary levels of heavy metals were divided by medians (As 29.72 μg/g cr, Cd 0.29 μg/g cr, Pb 2.60 μg/g cr), after logistic regression analysis, subjects with higher As exposure had the lower gene expressions of GPER1, PPARA and NR1I2. The higher Cd group had the higher gene expressions of AR, ESR2, GPER1 and PPARG. The higher Pb group had higher AHR and lower AR expressions. The CRP level was positively relevant to age and BMI. In addition, the results of partial least squares-structural equation modeling (PLS-SEM) indicated that young adults with higher levels of physiological indexes (age, arm, hip, BMI, and blood pressure) had higher CRP (path coefficient 0.485), and co-exposure of As, Cd and Pb presented higher gene expression of AHR and NR1I2 (path coefficient 0.335). Furthermore, the subjects with at least two potential CVD development syndromes inquired by TIA (transient ischemic attack) questionnaire and Rose questionaire had higher urinary Cd levels and decreased PPARA and NR1I2 expression. The findings of this study suggested that exposure to heavy metals relied on various types of dietary and living habit. Exposure to As, Cd and Pb might affect gene expression of hormone-related receptors (AR, ESR1, ESR2 and GPER1), lipometabolism-related receptors (PPARA and PPARG), and xenobiotic detoxification-related receptors (NR1I2 and AHR) to induce inflammatory response. Even though there was no correlation between exposure levels of heavy metals and CRP levels, subjects with CVD syndromes were observed to have higher urinary Cd levels and lower PPARA expression, indicating that Cd exposure might reduce PPARA expression to cause inflammation for CVD development. Therefore, it is necessary to reduce the chance of heavy metal exposure to avoid adverse health effect.