Adverse outcome pathway for the neurotoxicity of per- and polyfluoroalkyl substances: A systematic review

Eco-Environment & Health, Journal Year: 2024, Volume and Issue: 3(4), P. 476 - 493

Published: Aug. 30, 2024

Per- and polyfluoroalkyl substances (PFAS) are endocrine disruptors with unambiguous neurotoxic effects. However, due to variability in experimental models, population characteristics, molecular endpoints, the elucidation of mechanisms underlying PFAS-induced neurotoxicity remains incomplete. In this review, we utilized adverse outcome pathway (AOP) framework, a comprehensive tool for evaluating toxicity across multiple biological levels (molecular, cellular, tissue organ, individual, population), elucidate induced by PFAS. Based on 271 studies, reactive oxygen species (ROS) generation emerged as initiating event 1 (MIE1). Subsequent key events (KEs) at cellular level include oxidative stress, neuroinflammation, apoptosis, altered Ca

Language: Английский

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Exposure to PFOA, PFOS, and PFHxS induces Alzheimer's disease-like neuropathology in cerebral organoids

Environmental Pollution, Journal Year: 2024, Volume and Issue: 363, P. 125098 - 125098

Published: Oct. 9, 2024

Language: Английский

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Poly- and per-fluoroalkyl substances toxicity on skeletal and cognitive well-being: a comprehensive review

Journal of Environmental Science and Health Part C, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 25

Published: Feb. 20, 2025

Poly- and per-fluoroalkyl substances (PFAS) are a large group of synthetic compounds having wide array use in consumer products industries, such as fire suppressant foam, nonstick cookware, paper, water-proof textiles, surfactants, aeronautics, cosmetics. This widespread distribution PFAS, their capacity to accumulate living organisms, harmful effects represent rising concern for public health. A multitude studies have presented information on exposure PFAS broad spectrum adverse health outcomes through animal models observational studies. Here, we reviewed various that related toxicity bone brain its underlying mechanisms. well-established toxicological bone, reduced osteoblastic increased osteoclastic activity, activation peroxisome proliferator activated receptor-γ (PPAR-γ), expression WNT11. With respect brain, been linked with autism, somnolence, sleep disturbances, glioma, Alzheimer's, decreased cognition, Glycogen Synthase β (GSK3β). Further research is required several areas, age-specific impact other beyond perfluorooctane sulfonate (PFOS) perfluorooctanoic acid (PFOA), involvement proliferator-activated receptors PFAS-induced toxicity. Regarding toxicity, extensive adults there currently relative scarcity this age when compared the available conducted children older individuals.

Language: Английский

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Exploring the neurodegenerative potential of per- and polyfluoroalkyl substances through an adverse outcome pathway network

The Science of The Total Environment, Journal Year: 2025, Volume and Issue: 969, P. 178972 - 178972

Published: Feb. 28, 2025

While emerging evidence links per- and polyfluoroalkyl substances (PFAS) to neurotoxicity, their potential role in neurodegeneration remains poorly understood. Moreover, existing neurodegeneration-related adverse outcome pathways (AOPs) available on AOP-Wiki have not yet been integrated into a unified network. To address these gaps, this study aims develop the first AOP network utilize it explore possible contributions of long-chain legacy PFAS neurodegeneration, specifically concerning Alzheimer's Parkinson's diseases. A total 74 AOPs were screened from AOP-Wiki, which 13 met eligibility criteria incorporated We analyzed resulting using topological parameters such as in-degree, out-degree, eccentricity, betweenness centrality. elucidate mechanistic exposure neurodegenerative pathways, we linking key events (KEs) within The results highlighted increased intracellular calcium hub with highest connectivity followed by critical KEs neuronal apoptosis, oxidative stress, N-methyl-d-aspartate receptor (NMDA-R) overactivation, mitochondrial dysfunction. Consistent toxicological evidence, indicate that may adversely affect neurotransmitter systems, particularly through NMDA-R leading excitotoxicity. This result dyshomeostasis, dysfunction, inflammatory-oxidative cascades, neuroinflammation, cell death. By providing basis for understanding PFAS, offers crucial framework assessing risks associated chemicals inform future regulatory measures public health strategies. Further experimental validation is needed confirm animal models or human populations.

Language: Английский

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Maternal perfluoroalkyl and polyfluoroalkyl substances (PFAS) exposure and preeclampsia: a systematic review and meta-analysis

BMC Pregnancy and Childbirth, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 13, 2025

Polyfluoroalkyl and perfluoroalkyl substances (PFAS) are persistent organic pollutants exposure have been suggested with the risk of developing preeclampsia. Yet, evidence on associations PFAS preeclampsia is still conflicting. Thus, current study conducted a systematic review meta-analysis epidemiological linking maternal to This research methodology involved searching three electronic databases for studies, then conducting using random-effects model analyse heterogeneity between studies. The quality strength each exposure-outcome pair was also evaluated, as well bias. search identified 10 potentially eligible studies related blood level preeclampsia, which 7 were ultimately selected. Meta-analysis demonstrated association combined compounds in pregnant mother zero (I2=0.0%, Q= 3.09, df= 6, p=0.798). Preeclampsia found moderate perfluorooctanoic acid (PFOA) (Test overall effect: z=2.2, p=0.03; Test heterogeneity: I2=0.0%, 3.49, p=0.745) perfluorooctane sulfonate (PFOS) z=2.5, p=0.01; 3.70, p=0.718). showed significant PFOA PFOS However, in-depth investigation imperative elucidate impact different concentration types risk.

Language: Английский

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