Serum Phthalate Concentrations and Biomarkers of Oxidative Stress in Adipose Tissue in a Spanish Adult Cohort.

The relationship between phthalates, a group of chemical pollutants classified as endocrine disruptors, and oxidative stress is not fully understood. The aim of the present hospital-based study was to explore the associations between circulating levels of 10 phthalate metabolites and 8 biomarkers of oxidative stress in adipose tissue. The study population (n = 143) was recruited in two hospitals in the province of Granada (Spain). Phthalate metabolite concentrations were analyzed by isotope diluted online-TurboFlow-LC-MS/MS in serum samples, while oxidative stress markers were measured by commercially available kits in adipose tissue collected during routine surgery. Statistical analyses were performed by MM estimators' robust linear regression and weighted quantile sum regression. Mainly, positive associations were observed of monomethyl phthalate (MMP), monoiso-butyl phthalate (MiBP), and mono-n-butyl phthalate (MnBP) (all low molecular weight phthalates) with glutathione peroxidase (GPx) and thiobarbituric acid reactive substances (TBARS), while an inverse association was found between monoiso-nonyl phthalate (MiNP) (high molecular weight phthalate) and the same biomarkers. WQS analyses showed significant effects of the phthalate mixture on GSH (ß = -30.089; p-value = 0.025) and GSSG levels (ß = -19.591; p-value = 0.030). Despite the limitations inherent to the cross-sectional design, our novel study underlines the potential influence of phthalate exposure on redox homeostasis, which warrants confirmation in further research.

Associations of circulating levels of phthalate metabolites with cytokines and acute phase reactants in a Spanish human cohort.

The associations between human phthalate exposure and the onset of chronic diseases with an immunological component (e.g., metabolic syndrome, cancer) remain unclear, partly due to the uncertainties in the underlying mechanisms. This study investigates cross-sectional associations of the concentrations of 10 phthalate metabolites with 19 cytokines and acute phase proteins in 213 serum samples of Spanish adults. The associations were explored by Spearman's correlation, multivariable linear regression, and weighted quantile sum regression analyses. In the multivariable analyses, levels of plasminogen activator inhibitor (PAI)-1 were positively associated with mono-n-butyl phthalate (fold-change per one IQR increase in phthalate levels, 95% Confidence Interval: 1.65, 1.45-1.88) and mono-iso-butyl phthalate (3.07, 2.39-3.95), mono-ethyl phthalate (2.05, 1.62-2.61), as well as categorized mono-iso-decyl and mono-benzyl phthalates. The same phthalates also were significantly associated with leptin, interleukin (IL)-18 and monocyte chemoattractant protein-1. Moreover, the proinflammatory markers IL-1ß, IL-17, IL-8, IL-6, IL-12, tumor necrosis factor, and lipopolysaccharide-binding protein showed positive and negative associations with, respectively, mono-(2-ethyl-hexyl) and mono-methyl phthalates. Finally, phthalate mixtures were positively associated with PAI-1, leptin, IL-18, IL-12, IL-8 and IL-1ß. Despite the cross-sectional design limitation, these associations point to relevant subclinical immuno-inflammatory actions of these pollutants, warranting confirmation in future studies.

Differential Bioaccumulation Patterns of α, ß-Hexachlorobenzene and Dicofol in Adipose Tissue from the GraMo Cohort (Southern Spain).

To identify bioaccumulation patterns of α-, ß- hexachlorocyclohexane (HCH) and dicofol in relation to sociodemographic, dietary, and lifestyle factors, adipose tissue samples of 387 subjects from GraMo cohort in Southern Spain were analyzed. Potential predictors of these organochlorine pesticides (OCP) levels were collected by face-to-face interviews and assessed by multivariable linear and logistic regression. OCPs were detected in 84.2% (ß-HCH), 21.7% (α-HCH), and 19.6% (dicofol) of the population. ß-HCH levels were positively related to age, body mass index (BMI), mother's occupation in agriculture during pregnancy, living in Poniente and Alpujarras, white fish, milk and water consumption, and negatively related to being male, living near to an agricultural area, working ≥10 years in agriculture, and beer consumption. Detectable α-HCH levels were positively related to age, BMI, milk consumption, mother's occupation in agriculture during pregnancy, and negatively with residence in Poniente and Alpujarras, Granada city, and Granada Metropolitan Area. Residence near to an agricultural area, smoking habit, white fish and water consumption, and living in Poniente and Alpujarras, Granada city and Granada Metropolitan Area were negatively associated with detectable dicofol levels. Our study revealed different bioaccumulation patterns of α, ß-HCH and dicofol, probably due to their dissimilar period of use, and emphasize the need for assessing the exposure to frequently overlooked pollutants.

Adipose tissue cadmium concentrations as a potential risk factor for insulin resistance and future type 2 diabetes mellitus in GraMo adult cohort.

Adipose tissue has been recently highlighted as a promising matrix for evaluation of cadmium's (Cd) long-term exposure although not frequently considered in epidemiological studies. The association between Cd exposure and type 2 Diabetes Mellitus (T2DM) remains unclear. This work aimed to explore the association between adipose tissue Cd levels and T2DM incidence over a 16-year follow-up in an adult cohort from Southern Spain considering smoking status. We also performed complementary cross-sectional analyses focused on subclinical markers of glucose homeostasis at recruitment. Clinical information was obtained from hospital databases. Socio-demographic characteristics, lifestyle and diet were collected by face-to-face interviews. Homeostatic model assessment (HOMA) values of insulin sensitivity/resistance and ß-cell function were calculated using fasting serum glucose, insulin, and C-peptide levels at recruitment. Adipose tissue Cd concentrations were quantified by inductively coupled plasma mass spectrometry. Statistical analyses were performed by means of Cox-regression and multivariable linear regression models. Participants in the 4th quartile (Q4) of Cd concentrations showed a non statistically-significant increased T2DM risk (Hazard Ratio (HR) Q4 vs Q1: 1.97; 95% Confidence Interval (CI): 0.69, 5.66). This association was particularly strong and suggestive in current smokers (HR: 2.19; 95% CI: 0.98, 4.98). Interestingly, smokers in the 2nd tertile (T2) of adipose tissue Cd levels showed increased log-transformed insulin resistance (beta T2 vs T1: 0.52; 95% CI: 0.07, 0.97), as well as higher log-transformed insulin levels (beta T2 vs T1: 0.52; 95% CI: 0.08, 0.95). We found evidences supporting that Cd exposure, particularly from tobacco smoking, could be a risk factor for T2DM. In addition, our results support the potential relevance of adipose tissue as a matrix for Cd exposure assessment.