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BACKGROUND: Organophosphate esters (OPEs) are used as flame retardants and plasticizers. Oxidative stress, the imbalance of reactive oxygen species and antioxidants, measured prenatally has been associated with adverse birth outcomes including preeclampsia and preterm birth. We are the first study to investigate the relationship between OPEs and oxidative stress among pregnant women. METHODS: Pregnant women 18-40 yrs. were recruited in Northern Puerto Rico (n = 47) between 2011 and 2015. OPE concentrations of: bis(2-chloroethyl) phosphate (BCEtP), bis(1-chloro-2-propyl) phosphate (BCPP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), dibutyl phosphate (DNBP), and diphenyl phosphate (DPHP) and biomarkers for oxidative stress, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane were measured in urine up to three times during pregnancy. Associations between oxidative stress biomarkers and OPEs were assessed using linear mixed models adjusted for specific gravity, age, BMI, and income. RESULTS: Metabolites BCEtP, BDCPP, and DPHP were frequently detected (>97%). OPE metabolite concentrations remained stable over time (Intraclass correlation coefficients (ICCs): 0.51-0.60). Metabolites BCEtP, BCPP, and DPHP were associated with an increase in 8-isoprostane and OHdG. An interquartile range (IQR) increase in BDCPP was associated with a 21% increase in 8-isoprostane (p < 0.01), while and IQR increase in DPHP and BCPP was associated with a 12% increase (p = 0.04, p = 0.08, respectively). IQR increases in BDCPP and DPHP were also associated with an 18 and 19% increase in OHdG, respectively (p < 0.01). CONCLUSION: OPE metabolites were frequently detected and our results suggest that exposure to OPEs is associated with higher levels of oxidative stress. Further investigation into these relationships and birth outcomes is warranted.

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Abstract Introduction: Peripheral artery disease (PAD) is mainly caused by atherosclerosis but also involves hyperglycemia and dyslipidemia, which trigger oxidative stress and lead to vascular damage. Objectives: To determine the prevalence of PAD in patients with type 2 diabetes mellitus (DM2) and/or prediabetes and/or dyslipidemia, to identify some risk factors and to establish whether urinary levels of 8-isoprostane-f2α (an oxidative stress marker) are elevated in patients with PAD. Design: A cross-sectional, nonprobabilistic, convenience sampling study Materials and methods: The sample included 146 patients with DM2 and/or prediabetes and/ or dyslipidemias from the Universidad Nacional de Colombia. Risk factors, symptoms related to PAD, ankle-brachial index measurement and biochemical variables (HbA1c%, fasting blood glucose, lipid profile, creatinine and albuminuria) were recorded. Urine levels of 8-isoprostane-f2α were determined by ELISA. The 8-iso-PGF2α/creatine concentration were analyzed using the statistical package R. Risk factors were compared using ANOVA/ Kruskal-Wallis. ROC curves were generated to analyze the discriminant power of the biomarkers. The joint analysis of laboratory results and risk factors was performed using multivariate logistic regressions. Results: PAD was identified in 10 diabetic patients. Risk factors were smoking, dyslipidemia, poor metabolic control, overweight or obesity. There was no evidence of increased urinary 8-isoprostane-f2α in these subjects. Conclusions: A low prevalence of PAD was found in subjects with DM2. There was no evidence of increased 8-isoprostane-f2α measured by ELISA in patients with PAD. The extension of the study with different markers of oxidative stress and the use of other techniques is recommended (Acta Med Colomb 2019; 44. DOI: https://doi.org/10.36104/amc.2019.1257).

Resumen Introducción: la enfermedad arterial periférica (EAP) es causada principalmente por aterosclerosis e intervienen la hiperglucemia y dislipidemia que desencadenan estrés oxidativo y daño vascular. Objetivo: determinar la prevalencia de EAP en pacientes con diabetes mellitus tipo 2 (DM2) y/o prediabetes y/o dislipidemias, así como algunos factores de riesgo; también, establecer si los niveles urinarios de 8-isoprostano-f2α (marcador de estrés oxidativo) están elevados en pacientes con EAP. Diseño: estudio de tipo transversal, no probabilístico, de conveniencia. Material y métodos: la muestra comprendió 146 pacientes con DM2 y/o prediabetes y/o dislipidemias de la Universidad Nacional de Colombia. Se registraron factores de riesgo, síntomas relacionados con EAP, medida índice tobillo-brazo y variables bioquímicas (HbA1c%, glucemia basal, perfil lipídico, creatinina y albuminuria). Se determinaron niveles en orina de 8-isoprostano-f2α por ELISA. Los resultados de la concentración de 8-iso-PGF2α/creatinuria se analizaron mediante el paquete estadístico R. La comparación de factores de riesgo se analizó mediante ANOVA/Kruskal-Wallis. Se generaron curvas ROC para analizar el poder discriminante del biomarcador. El análisis conjunto de resultados de laboratorios y de factores de riesgo se realizó mediante regresiones logísticas multivariantes. Resultados: se evidenció prevalencia de EAP en 10 pacientes diabéticos. Como factores de riesgo se encontraron: fumar, dislipidemia, mal control metabólico, sobrepeso u obesidad. No se evidenció aumento del 8-isoprostano-f2α urinario en estos sujetos. Conclusiones: se encontró baja prevalencia de EAP en los sujetos con DM2. No se evidenció aumento del 8-isoprostano-f2α medido por ELISA en pacientes con EAP. Se recomienda ampliar el estudio con diferentes marcadores de estrés oxidativo y uso de otras técnicas. (Acta Med Colomb 2019; 44. DOI: https://doi.org/10.36104/amc.2019.1257).

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Oxidative stress has been linked to many obesity-related conditions among children including cardiovascular disease, diabetes mellitus and hypertension. Exposure to environmental chemicals such as phthalates, ubiquitously found in humans, may also generate reactive oxygen species and subsequent oxidative stress. We examined longitudinal changes of 8-isoprostane urinary concentrations, a validated biomarker of oxidative stress, and associations with maternal prenatal urinary concentrations of phthalate metabolites for 258 children at 5, 9 and 14 years of age participating in a birth cohort residing in an agricultural area in California. Phthalates are endocrine disruptors, and in utero exposure has been also linked to altered lipid metabolism, as well as adverse birth and neurodevelopmental outcomes. We found that median creatinine-corrected 8-isoprostane concentrations remained constant across all age groups and did not differ by sex. Total cholesterol, systolic and diastolic blood pressure were positively associated with 8-isoprostane in 14-year-old children. No associations were observed between 8-isoprostane and body mass index (BMI), BMI Z-score or waist circumference at any age. Concentrations of three metabolites of high molecular weight phthalates measured at 13 weeks of gestation (monobenzyl, monocarboxyoctyl and monocarboxynonyl phthalates) were negatively associated with 8-isoprostane concentrations among 9-year olds. However, at 14 years of age, isoprostane concentrations were positively associated with two other metabolites (mono(2-ethylhexyl) and mono(2-ethyl-5-carboxypentyl) phthalates) measured in early pregnancy. Longitudinal data on 8-isoprostane in this pediatric population with a high prevalence of obesity provides new insight on certain potential cardiometabolic risks of prenatal exposure to phthalates.

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Nearly half of the world's population is exposed to household air pollution (HAP) due to long hours spent in close proximity to unvented cooking fires. The effect of woodsmoke exposure on oxidative stress was examined by investigating the association between woodsmoke exposure and biomarkers of DNA oxidation (8-hydroxy-2'-deoxyguanosine [8-OHdG]) and lipid peroxidation (8-isoprostane) among control and intervention stove users. HAP exposure assessment was conducted within the framework of a community-randomized controlled trial of 51 communities in San Marcos Province, Cajamarca Region, Peru. The first morning urine voids after 48h HAP exposure assessment from a subset of 45 control and 39 intervention stove users were analyzed for 8-OHdG and 8-isoprostane. General linear models and correlation analyses were performed. Urinary oxidative stress biomarkers ranged from 11.2 to 2270.0µg/g creatinine (median: 132.6µg/g creatinine) for 8-OHdG and from 0.1 to 4.5µg/g creatinine (median: 0.8µg/g creatinine) for 8-isoprostane among all study subjects (n=84). After controlling for the effects of traffic in the community and eating food exposed to fire among all subjects, cooking time was weakly, but positively associated with urinary 8-OHdG (r=0.29, p=0.01, n=80). Subjects' real-time personal CO exposures were negatively associated with 8-OHdG, particularly the maximum 30-second CO exposure during the sampling period (r=-0.32, p=0.001, n=73). 48h time integrated personal PM2.5 was negatively, but marginally associated with urinary 8-isoprostane (r=-0.21, p=0.09, n=69) after controlling for the effect of distance of homes to the road. Urinary 8-isoprostane levels reported in the available literature are comparable to results found in the current study. However there were relatively high levels of urinary 8-OHdG compared to data in the available literature for 8-OHdG excretion. Results suggest a sustained systemic oxidative stress among these Peruvian women chronically exposed to wood smoke.

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