Chapter 7. Impact of Phthalates on Oxidative Stress Metabolism: A Key Mechanism Contributes to the Disease Pathogenesis


Duygu Aydemir and Nuriye Nuray Ulusu
Koc University, School of Medicine, Department of Medical Biochemistry, Sariyer, Istanbul, Turkey
Koç University Research Center for Translational Medicine (KUTTAM), Sariyer, Istanbul, Turkey

Chapter DOI: 10.52305/MMXP2149
Part of the Book: Phthalates: Environmental and Health Effects


Endocrine-disrupting chemicals (EDCs) are xenobiotics found in almost all types of industrial products such as toys, pharmaceuticals, cosmetics, food wrappings, furniture, paints, solvents, plasticizer, and households. Phthalates are the most used chemicals in the industry belonging to the EDCs family. Di(2-ethylhexyl) phthalate (DEHP), di-isononyl phthalate (DiNP), di-n-octyl phthalate (DnOP), diethyl phthalate (DEP), dibutyl phthalate (DBP), dimethyl phthalate (DMP), di-n-butyl phthalate (DnBP), benzyl butyl phthalate (BzBP), di-isobutyl phthalate (DiBP) and di-isodecyl phthalate (DiDP) belong to the phthalate family and cause adverse health effects by altering hormone metabolism on human and wildlife. Phthalates have different mechanisms to alter hormone metabolism, including mimicking or antagonizing hormones, altering hormone synthesis, dysregulation of hormone transport, and activation/repression of hormone receptors. Phthalates are metabolized by skin esterases, gut, liver, and kidneys; however, metabolized products of phthalates are very harmful, and some parts of phthalates accumulate in the body without being metabolized. Besides impaired hormone metabolism, phthalates alter oxidative stress metabolism via reducing antioxidant defense, interfering with detoxification pathways, and altering energy metabolism. Peroxisome-proliferator-activated receptors (PPARs) comprise three subtypes (PPARα, δ, and γ) and main regulators of carbohydrate, protein, and oxidative stress metabolisms. Phthalates can bind to PPAR receptors and activate them, causing elevated levels of oxidative stress in the cell. Besides, phthalates may interfere with anti-oxidant enzymes, including glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), glutathione s-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), thioredoxin family, and glutathione peroxidase (GPx) leading to the impaired redox balance in the cell. Oxidative stress is characterized by reduced antioxidant defense and enhanced reactive oxygen species (ROS) contributing to the pathogenesis of various diseases, including diabetes mellitus (DM), cancer, obesity, metabolic syndrome, infertility, cardiovascular diseases, and cancer. This chapter discusses the impact of phthalates on the oxidative stress metabolism involved in the pathogenesis of various diseases, including fertility, metabolic syndrome, diabetes mellitus, cardiovascular diseases, and cancer.

Keywords: phthalates, oxidative stress, antioxidant defense, detoxification, disease pathogenesis


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