Contribution of sociodemographic, occupational, lifestyle and dietary characteristics to the oxidative stress microenvironment in adipose tissue.

The present study was conceived on the basis of the few previous reports suggesting a potential relevance of the oxidative stress microenvironment in the adipose tissue, a biological matrix which is closely related to the development of several chronic pathologies. Thus, our aim was to describe the levels of enzymatic and non-enzymatic antioxidants and markers of oxidative damage in adipose tissue samples from a Spanish cohort, as well as their main sociodemographic, lifestyle, and dietary predictors. The study was conducted in a subsample (n = 271 adults) of GraMo cohort, recruited in Granada (Southern Spain). A face-to-face questionnaire was used to gather data regarding sociodemographic characteristics, lifestyle, dietary habits, health status, and perceived exposure to chemicals. We analyzed adipose tissue levels of lipid peroxidation (TBARS), total superoxide dismutase (SOD) activity, heme oxygenase-1 (HO-1) activity, and glutathione cycle biomarkers. Potential predictors of oxidative stress markers were assessed using stepwise multivariable linear regression analyses. SOD and TBARS levels were mainly related to sociodemographic and occupational characteristics, while the components of the glutathione cycle and HO-1 were predominantly associated with dietary habits. Men showed significantly lower levels of oxidative stress levels than women. In the regression models including only women, the use of oral contraceptive and hormonal therapy was associated with lower levels of oxidative stress, while the number of children was positively associated with increased oxidative biomarkers. Our results suggest that adipose tissue is potentially important matrix for the assessment of oxidative stress, which can be affected by specific environmental factors. These findings might be relevant for public health.

Contribution of Persistent Organic Pollutant Exposure to the Adipose Tissue Oxidative Microenvironment in an Adult Cohort: A Multipollutant Approach.

Despite growing in vitro and in vivo evidence of the putative role of persistent organic pollutants (POPs) in the induction of oxidative damage in cell structures, this issue has been poorly addressed from an epidemiologic perspective. The aim of this study was to explore associations between adipose tissue POP concentrations and the in situ oxidative microenvironment. A cross-sectional study was conducted in a subsample (n = 271) of a previously established cohort, quantifying levels of eight POPs and four groups of oxidative stress biomarkers in adipose tissue. Associations were explored using multivariate linear regression analyses adjusted for potential confounders. We assessed the combined effect of POPs on oxidative stress/glutathione system biomarkers using weighted quantile sum regression (WQS). Increased concentrations of p,p'-DDE, HCB, ß-HCH, dicofol, and PCBs (congeners -138, -153, and -180) were predominantly associated with higher lipid peroxidation (TBARS) [exp(ß) = 1.09-1.78, p < 0.01-0.04)] and SOD activity [exp(ß) = 1.13-1.48, p < 0.01-0.05)] levels. However, only a few associations were observed with glutathione system biomarkers, e.g., PCB-180 with total glutathione [exp(ß) = 1.98, p = 0.03]. The WQS index was found to be positively associated with SOD activity, and PCB-138, PCB-180, and ß-HCH were the main contributors to the index. Likewise, the WQS index was positively associated with TBARS levels, with the three PCBs acting as the main contributors. This is the first epidemiological evidence of the putative disruption by POPs of the adipose tissue oxidative microenvironment. Our results indicate that POP exposure may enhance alternative pathways to the glutathione detoxification route, which might result in tissue damage. Further research is warranted to fully elucidate the potential health implications.

A novel biomarker for anti-androgenic activity in placenta reveals risks of urogenital malformations.

It has been hypothesized that the rise in male reproductive disorders over recent decades may at least be partially attributable to environmental factors, including chemical exposures, but observed associations with single chemicals were rather weak. The aim of this case-control study was to explore the relationship between exposure to mixtures of (anti-)androgenic chemicals during pregnancy and the risk of cryptorchidism and/or hypospadias in offspring, using the total effective xenobiotic burden of anti-androgens (TEXB-AA) as a biomarker. A subsample of 29 cases (16 of cryptorchidism, 12 of hypospadias, and one of both disorders) and 60 healthy controls was nested in a cohort of male newborns recruited between October 2000 and July 2002. The (anti-)androgenic activity of placenta samples collected at delivery was assessed using TEXB-AA biomarker, combined with a bioassay-directed fractionation protocol that separated endogenous hormones from most (anti-)androgenic chemicals by normal-phase HPLC. The bioassay measures the androgen-induced luciferase activity and the inhibition of this pathway by (anti-)androgens. First, we collected 27 HPLC fractions in each placenta extract, which were all tested in the bioassay. The multivariable statistical analyses indicated a statistically significant positive dose-response association between the potent anti-androgenic activity of the HPLC fraction collected during minutes 1-2 (F2) and the risk of malformations (odds ratio: 2.33, 95% CI: 1.04-5.23). This study represents a novel approach for the estimation of combined effects of the total anti-androgenic load and the associations suggest an effect of environmental pollutants on the development of fetal reproductive tract.Free Spanish abstract: A Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/149/6/605/suppl/DC1.