Paraoxonase-1 and Early-Life Environmental Exposures

• Main Authors: Judit Marsillach, Lucio G. Costa, Clement E. Furlong
• Format: Article
• Language: English
• Published: Levy Library Press 2016-06-01
• Series: Annals of Global Health
• Subjects: early-life exposures; environmental health; organophosphates; neurodevelopment; paraoxonase-1
• Online Access: https://annalsofglobalhealth.org/articles/1166

Acute and chronic exposures to widely used organophosphorus (OP) insecticides are common. Children's <a title="Learn more about Detoxification" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/detoxification">detoxification</a> mechanisms are not well developed until several years after birth. The increased cases of <a title="Learn more about Neurodevelopmental disorder" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/neurodevelopmental-disorder">neurodevelopmental disorders</a> in children, together with their increased susceptibility to OP <a title="Learn more about Neurotoxicity" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/neurotoxicity">neurotoxicity</a> cannot be explained by genetic factors alone but could be related to <a title="Learn more about Gene-environment Interactions" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/gene-environment-interactions">gene-environment interactions</a>. Paraoxonase-1 (PON1) is an enzyme that can detoxify OPs but its catalytic efficiency for hydrolysis to certain OPs is modulated by the Q192R polymorphism. Studies with animals have provided important information on the role of PON1 in protecting against <a title="Learn more about Gestational age" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/gestational-age">gestational</a> and postnatal toxicity to OPs. The 'PON1''Q192' <a title="Learn more about Allele" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/allele">allele</a> is less efficient in hydrolyzing certain OPs than the 'PON1''R192'allele. Maternal PON1 status (PON1 activity levels, the most important measurement, and functional Q192R phenotype) modulates the detrimental effects of exposure to the OP chlorpyrifos oxon on fetal brain gene expression and biomarkers of exposure. Epidemiologic studies suggest that children from mothers with lower PON1 status who were in contact with OPs during pregnancy tend to show smaller head circumference at birth and adverse effects in <a title="Learn more about Cognitive Function" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/cognitive-function">cognitive function</a> during childhood. Infants and children are vulnerable to OP toxicity. The detrimental consequences of OPs on <a title="Learn more about Neural development" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/neural-development">neurodevelopment</a> can lead to future generations with permanent cognitive problems and susceptibility to develop <a title="Learn more about Neurodegeneration" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/neurodegeneration">neurodegenerative diseases</a>. Improved methods using mass spectrometry to monitor OP-adducted biomarker proteins are needed and will be extremely helpful in early life biomonitoring, while measurement of PON1 status as a biomarker of susceptibility will help identify mothers and children highly sensitive to OPs. The use of adductomics instead of <a title="Learn more about Enzyme assay" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/enzyme-assay">enzymatic activity</a> assays for biomonitoring OP exposures have proved to provide several advantages, including the use of <a title="Learn more about Dried blood spot" href="https://www.sciencedirect.com/topics/medicine-and-dentistry/dried-blood-spot">dried blood spots</a>, which would facilitate monitoring newborn babies and children.