“Oxidative stress induced by phthalates in mammals: State of the art and potential biomarkers”
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Background: Phthalates, plasticizers that are widely used in consumer products including toys, cosmetics, and food containers, have negative effects in liver, kidney, brain, lung and reproductive system of humans and other mammals. Objectives: To summarize, describe and discuss the available information on the effects of phthalate exposure in mammals, with emphasis on oxidative stress, and to suggest potential biomarkers of the health risks associated with phthalate exposure. Methods: An assessment of scientific journals was performed using the PRISMA model for systematic reviews. Manuscripts reporting effects of phthalate exposure on mammalian health published in the last decade were selected according to originality, content, and association to health hazards. Results and discussion: We identified 25 peer-reviewed articles published between January 1st, 2010 and June 1st, 2021 that fit the aims and selection criteria. Phthalates induce oxidative stress and cell degenerative processes by increasing intracellular reactive species. Antioxidant cytoprotective systems decrease with time of exposure; conversely, oxidative damage markers, including thiobarbituric acid-reactive substances (TBARS), 8-hydroxy-2′-desoxyguanosine (8-OHdG) and malondialdehyde (MDA), increase. Phthalates were associated with endocrine system disfunction, metabolic disorders, infertility, nonviable pregnancy, cell degeneration, growth impairment, tumor development, and cognitive disorders. Phthalates can also aggravate health conditions such as asthma, hepatitis, diabetes, allergies, chronic liver and kidney diseases. Among humans, the more vulnerable subjects to phthalate exposure effects were children and individuals with a prior health condition. Conclusion: Chronic exposure to phthalates induces oxidative stress in mammals with concomitant adverse effects in reproductive, respiratory, endocrine, circulatory, and central nervous systems in both in vitro and in vivo trials. Oxidative damage markers and phthalate metabolites levels were the most common biomarkers of phthalate exposure effects. Studies in free-ranging and wild mammals are nil. Further studies on the pathways that lead to metabolic disruption are needed to identify potential treatments against phthalate-induced detrimental effects. © 2021 Elsevier Inc.
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Antioxidants; Biomarkers; Ecotoxicology; Mammalian health; Oxidative stress; Phthalates; Reactive oxygen species 24 dehydrocholesterol reductase; 8 hydroxydeoxyguanosine; 8 isoprostane; aldehyde oxidase; alpha tocopherol; aspartate aminotransferase; C reactive protein; calcitonin gene related peptide; gamma glutamyltransferase; glutaredoxin; glutathione; glutathione peroxidase; heme oxygenase 1; hydrocortisone; immunoglobulin E; interleukin 4; lipocortin 5; malonaldehyde; mitogen activated protein kinase; mono(2 ethyl 5 hydroxyhexyl)phthalate; mono(2 ethyl 5 oxohexyl)phthalate; nicotinamide adenine dinucleotide phosphate quinone oxidoreductase; nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1; nitric oxide synthase; peroxiredoxin 6; phthalic acid; phthalic acid 2 ethylhexyl monoester; phthalic acid bis(2 ethylhexyl) ester; phthalic acid dibutyl ester; phthalic acid dimethyl ester; prion protein; prostaglandin synthase; reactive oxygen metabolite; scavenger receptor A; scavenger receptor class a member 3; superoxide dismutase; thiobarbituric acid reactive substance; thioredoxin reductase 1; thyroglobulin; transcription factor Nrf2; unclassified drug; xenobiotic agent; biological marker; phthalic acid; phthalic acid derivative; antioxidant; biomarker; ecotoxicology; health risk; mammal; oxidative stress; phthalate; reactive oxygen species; 4 nitroquinoline 1 oxide-transformed cell line; adult; animal experiment; animal model; antioxidant activity; asthma; atopic dermatitis; blood analysis; carcinogenesis; cell degeneration; cell protection; child; clinical assessment; cognitive defect; controlled study; depression; diabetes mellitus; ecotoxicology; endocrine disease; environmental exposure; female; Hashimoto disease; health hazard; hepatitis; human; in vitro fertilization; infertility; insulin resistance; kidney disease; liver disease; liver fibrosis; liver necrosis; long term exposure; mammal; medical information; metabolic disorder; mouse; nonhuman; oxidative stress; peer review; placenta; pregnancy; rat; respiratory tract inflammation; Review; systematic review; thyroid disease; tissue injury; urinalysis; adverse event; animal; metabolism; oxidative stress; Animals; Biomarkers; Child; Environmental Exposure; Female; Humans; Mammals; Oxidative Stress; Phthalic Acids; Pregnancy
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