Prenatal and breastfeeding exposure to low dose of diethylhexyl phthalate induces behavioral deficits and exacerbates oxidative stress in rat hippocampus

Safarpour, Soheila; Zabihi, Ebrahim; Ghasemi-Kasman, Maryam; Nosratiyan, Nasrin; Feizi, Farideh

doi:10.1016/j.fct.2021.112322

Cited by 22 publications

(9 citation statements)

References 60 publications

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“…DEHP can aggravate mitochondrial damage and enhance cytotoxicity by increasing the production of ROS and promoting mitochondrial fragmentation 50 . Low dose DEHP prenatal and lactation exposure can aggravate oxidative stress and behavioral defects in hippocampus of rats 51 . Meanwhile, studies have also confirmed that MPs can cause hepatotoxicity and disrupt lipid metabolism in liver organs by increasing levels of oxidative stress, inducing ROS and promoting inflammatory reactions, 52,53 and inducing oxidative stress in rat cardiomyocytes and further leading to cardiac dysfunction 54 .…”

Section: Discussionmentioning

confidence: 99%

“…50 Low dose DEHP prenatal and lactation exposure can aggravate oxidative stress and behavioral defects in hippocampus of rats. 51 Meanwhile, studies have also confirmed that MPs can cause hepatotoxicity and disrupt lipid metabolism in liver organs by increasing levels of oxidative stress, inducing ROS and promoting inflammatory reactions, 52,53 and inducing oxidative stress in rat cardiomyocytes and further leading to cardiac dysfunction. 54 In this study, we also found that DEHP and MPs could induce oxidative stress in mouse liver and significantly increase ROS level, which also became the upstream mechanism of liver toxic damage caused by DEHP and MPs.…”

Section: Discussionmentioning

confidence: 99%

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Di(2‐ethylhexyl) phthalate and microplastics cause necroptosis and apoptosis in hepatocytes of mice by inducing oxidative stress

Chen

Zhang

et al. 2023

Environmental Toxicology

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Di(2‐ethylhexyl) phthalate (DEHP) is a plasticizer and an endocrine disruptor. Microplastics (MPs) are pathogenic small plastic particles and abundant in the aqueous environment. The problem of residual hazards of plastic products is worthy of study, especially the joint exposure of a variety of plastic‐related products to the toxic effect. We used 200 mg/kg DEHP and 10 mg/L MPs to establish exposure model in vivo and 2 mM DEHP and 200 μg/L MPs to establish AML12 cell exposure model in vitro. In vivo study results showed that compared with the control group (NC) group, DEHP and MPs significantly increased the contents of malondialdehyde and hydrogen peroxide, and significantly decreased the contents of glutathione and the activity of superoxide dismutase, total antioxidant capacity, catalase and glutathione peroxidase. The level of oxidative stress was further aggravated after combined exposure. The reactive oxygen species level of AML12 exposed to DEHP and MPs in vitro was significantly higher than NC group, and the combined exposure was significantly higher than the single exposure. The in vivo and in vitro also confirmed that DEHP and MPs could significantly increase the mRNA and protein levels of apoptosis markers and necroptosis markers and there was an additive effect. After N‐acetylcysteine treatment in vitro, the above‐mentioned oxidative stress level and cell damage decreased significantly. This study provided a reference for advocating the reduction of the mixed use of plastic products, and provided a basis for preventing the harm of plastic products residues.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Di(2‐ethylhexyl) phthalate and microplastics cause necroptosis and apoptosis in hepatocytes of mice by inducing oxidative stress

Chen

Zhang

et al. 2023

Environmental Toxicology

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“…The most studied brain region was the hippocampus with a few studies focusing also on the medial prefrontal cortex (Tables 2, 3). Prenatal/Postnatal Exposure Two studies assessing spatial memory in the MWM showed an increased latency or traveled distance to reach the platform and reduced time spent in the target quadrant in rats exposed to DEHP at 5 μg/kg/day [17] or 1.25 mg/kg/day [19]. These behavioral changes were associated in the adult hippocampus with reduced gene expression of insulin and its signaling pathway involving phospho-Akt and phospho-glycogen synthase (2022) Reduced AR protein levels in microvessel-enriched fractions for DEHP-50 and mixture groups Increased gelatinaseimmunoreactivity and reduced laminin α-1 immunoreactivity for DEHP-5, 50, and mixture groups Reduced type IV collagen (COL-IVα-1) amount in hypothalamic microvesselenriched fraction for DEHP-5, 50, and mixture groups, reduced beta-dystroglycanimmunofluorescence for DEHP-50 in the mPOA.…”

Section: Learning and Memory And Related Neural Processesmentioning

confidence: 99%

“…Two studies assessing spatial memory in the MWM showed an increased latency or traveled distance to reach the platform and reduced time spent in the target quadrant in rats exposed to DEHP at 5 μg/kg/day [17] or 1.25 mg/kg/day [19]. These behavioral changes were associated in the adult hippocampus with reduced gene expression of insulin and its signaling pathway involving phospho-Akt and phospho-glycogen synthase kinase 3 beta (GSK3β) [19].…”

Section: Behavioral and Neuroendocrine Effects Of Phthalatesmentioning

confidence: 99%

Exposure to Low Doses of Phthalates in Male Rodents: Effects on Reproductive and Cognitive Behaviors

Ducroq,

Grange-Messent,

Mhaouty-Kodja

2023

Neuroendocrinology

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The nervous system is a sensitive target for exposure to environmental endocrine-disrupting compounds (EDC). This vulnerability is particularly important during the critical windows of development and puberty and lasts even at later stages of life. Among these environmental EDC, phthalates have largely been described for their neurotoxic effects. These effects have been reported for a large majority of studies using high to very-high doses of these substances, which are not relevant for environmental exposure. The aim of this review is to analyze specifically the male rodent studies using low doses of phthalates. This analysis focuses on reproductive and cognitive behaviors, given the described anti-androgenic effects of phthalates and the known regulation of these behaviors by sex steroids. We also analyze the other neural effects in the hypothalamus and hippocampus, the brain regions governing these behaviors. A particular focus is on the neurovascular unit, which is newly investigated in the field of endocrine disruption.

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“…The action of aromatase in male rats (postnatal days (PND) 1) was hampered in low concentrations of DEHP (less than 0.405 mg/kg/day) and raised in high concentrations (more than 15 mg/kg/day) [ 38 ]. In our recent study, DEHP exposure at low doses during pregnancy and lactation (GD 0- PND 21) caused memory impairment in the adult offspring rats [ 39 ]. Actually, DEHP changes the hippocampal lipid profile and results in higher levels of sphingomyelin and phosphatidylcholine in the female compared to the male mice.…”

Section: Effects Of Dehp Exposure On Nervous System Function Of Animalsmentioning

confidence: 99%

Effects of Di-2-Ethylhexyl Phthalate on Central Nervous System Functions: A Narrative Review

Safarpour

Ghasemi-Kasman

Safarpour

et al. 2022

Self Cite

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Background: Di-2-Ethylhexyl phthalate (DEHP) is one of the essential phthalate metabolites that disrupt the function of endocrine glands and causes numerous effects on animals, humans, and the environment. Phthalates are widely used in the plastics industry. Low doses of DEHP increase neurotoxicity in the nervous system that has arisen deep concerns due to the widespread nature of DEHP exposure and its high absorption during brain development. Objective: This review article evaluated the impacts of DEHP exposure from birth to adulthood on neurobehavioral damages. Then, the possible mechanisms of DEHP-induced neurobehavioral impairment were discussed. Methodology: Peer-reviewed articles were extracted through Embase, PubMed, and Google Scholar till the year 2021. Results: The results showed that exposure to DEHP during pregnancy and infancy leads to memory loss and irreversible nervous system damage. Conclusion: Overall, it seems that increased levels of oxidative stress and inflammatory mediators possess a pivotal role in DEHP-induced neurobehavioral impairment.

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Prenatal and breastfeeding exposure to low dose of diethylhexyl phthalate induces behavioral deficits and exacerbates oxidative stress in rat hippocampus

Cited by 22 publications

References 60 publications

Di(2‐ethylhexyl) phthalate and microplastics cause necroptosis and apoptosis in hepatocytes of mice by inducing oxidative stress

Di(2‐ethylhexyl) phthalate and microplastics cause necroptosis and apoptosis in hepatocytes of mice by inducing oxidative stress

Exposure to Low Doses of Phthalates in Male Rodents: Effects on Reproductive and Cognitive Behaviors

Effects of Di-2-Ethylhexyl Phthalate on Central Nervous System Functions: A Narrative Review

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