Rotenone, an environmental toxin, causes abnormal methylation of the mouse brain organoid's genome and ferroptosis

Huang, Yongyi; Liu, Xin; Feng, Yanjun; Nie, Xiaoli; Liu, Qiang; Du, Xin; Wu, Yuncheng; Liu, Te; Zhu, Xiaoying

doi:10.7150/ijms.74569

Cited by 18 publications

(9 citation statements)

References 49 publications

(83 reference statements)

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“…CHI promoted ferroptosis in hepatocytes by activating the ferroptosis-promoting protein p53 and disrupting the balances of TFR and ferroportin 1 (FPN-1). Similar ferroptotic cell death was observed in mouse brain organoids (mBOs) derived from neural stem cells exposed to rotenone, an insecticide . The upregulation of p53 and downregulation of GPX4 were responsible for rotenone-induced neurotoxicity.…”

Section: Ferroptosis Inducers In Environmental Pollutantsmentioning

confidence: 71%

“…Similar ferroptotic cell death was observed in mouse brain organoids (mBOs) derived from neural stem cells exposed to rotenone, an insecticide. 109 The upregulation of p53 and downregulation of GPX4 were responsible for rotenone-induced neurotoxicity. Furthermore, pesticides may interact with certain absorbents (e.g., MNPs) in the soil and affect earthworms.…”

Section: Airborne Particulate Matter (Pm)mentioning

confidence: 99%

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Ferroptosis Induced by Pollutants: An Emerging Mechanism in Environmental Toxicology

Yang,

Cai,

2024

Environ. Sci. Technol.

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Environmental pollutants have been recognized for their ability to induce various adverse outcomes in both the environment and human health, including inflammation, apoptosis, necrosis, pyroptosis, and autophagy. Understanding these biological mechanisms has played a crucial role in risk assessment and management efforts. However, the recent identification of ferroptosis as a form of programmed cell death has emerged as a critical mechanism underlying pollutant-induced toxicity. Numerous studies have demonstrated that fine particulates, heavy metals, and organic substances can trigger ferroptosis, which is closely intertwined with lipid, iron, and amino acid metabolism. Given the growing evidence linking ferroptosis to severe diseases such as heart failure, chronic obstructive pulmonary disease, liver injury, Parkinson's disease, Alzheimer's disease, and cancer, it is imperative to investigate the role of pollutant-induced ferroptosis. In this review, we comprehensively analyze various pollutant-induced ferroptosis pathways and intricate signaling molecules and elucidate their integration into the driving and braking axes. Furthermore, we discuss the potential hazards associated with pollutant-induced ferroptosis in various organs and four representative animal models. Finally, we provide an outlook on future research directions and strategies aimed at preventing pollutant-induced ferroptosis. By enhancing our understanding of this novel form of cell death and developing effective preventive measures, we can mitigate the adverse effects of environmental pollutants and safeguard human and environmental health.

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Section: Ferroptosis Inducers In Environmental Pollutantsmentioning

confidence: 71%

Section: Airborne Particulate Matter (Pm)mentioning

confidence: 99%

Ferroptosis Induced by Pollutants: An Emerging Mechanism in Environmental Toxicology

Yang,

Cai,

2024

Environ. Sci. Technol.

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“…A major contributing factor is believed to be unexpected epigenetic alterations resulting from inadequate maintenance of the original stem cells. 25,26 As the name implies, there is no change in the primary sequence of the genes itself, but the alterations can be passed on to daughter cells. 27 This becomes particularly concerning when PSCs undergo guided differentiation, where differentiation factors, including small molecules, produce off-target effects that ultimately affect cell fate.…”

Section: Environmental Science and Technology Lettersmentioning

confidence: 99%

“…The failure to maintain reproducibility is increasingly recognized as one of the significant challenges in stem-cell-based in vitro models. A major contributing factor is believed to be unexpected epigenetic alterations resulting from inadequate maintenance of the original stem cells. , …”

Section: Organoid-based Models In Environmental Toxicologymentioning

confidence: 99%

Human-Organoid-Based In Vitro Modeling for Environmental Toxicology

Kwak,

Peng

2024

Environ. Sci. Technol. Lett.

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Environmental pollutants pose significant health risks and elevate the likelihood of developing diseases. Organoid-based models offer the potential to transform environmental toxicology by offering platforms that closely mimic human physiology for precise toxicological assessments. Here, we discuss recent studies utilizing human-derived organoids as a preferable in vitro model for screening environmental toxins. We also address the persistent challenges arising from the pluripotent nature of their cellular origin. Furthermore, we emphasize future perspectives regarding the utility of organoids in understanding the intricate interactions between environmental pollutant exposure and human health by considering both ad hoc modifications and post hoc analyses. Overall, exploring human-organoid-based in vitro models holds promise for environmental toxicology, offering reproducible, reliable, and relevant data comparable to those from in vivo studies.

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“…Different classes of environmental pollutants affect the effectiveness of complex behaviours in different taxa both in model studies and in the environment (Scott & Sloman, 2004;Basu, 2012). In addition, exposure to neurotoxic compounds can provoke the deregulation of epigenetic pathways that control long-term adaptation mechanisms and the regulation of multi-or transgenerational effects (Valinluck et al, 2004;Wright & Baccarelli 2007;Huang et al, 2022). Several thousand types of xenobiotics have recently been identified as potential neurotoxins (Brack et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Cypermethrin induces neurotoxicity via inhibition of glial cell viability and apoptosis initiation

Sukharenko,

Gasso

2022

TAVM

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The progress in agricultural productivity is accompanied by the increase in the global application of pesticides. Moreover, the number of different pesticides used is growing permanently all over the world. Several types of pesticides are effective tools to suppress the propagation of insects, bacteria, and fungi. However, they could correlate with toxicity for other non-targeted organisms including mammalian and humans. Neurotoxicity is considered to be the most detrimental effect of pesticides given the ecotoxicology studies of the environmental pollution consequences for the last decades. Exposure to neurotoxic pesticides can induce multiple harmful disturbances in the deregulation of vital molecular pathways, cellular response, and programmed cell death initiation as well as lead to a decline in the functioning of the central neural system (CNS). All of them are potent in inhibiting the adaptation mechanisms and viability of vertebrate populations. The pyrethroids are the most total used group of pesticides. This study of the neurotoxic effects of pyrethroids aimed to contribute to assessing the risk rate in the application of compromised chemicals in agriculture production. Glial cells are the prevailing population in the CNS. Measurement of the cytotoxic effect of pollutants can be assessed by their neurotoxicity in glial cell culture. In the present study, we detected glioma U251 cells' viability, oxidative stress indices, and a mitochondria-associated marker of apoptosis to evaluate the molecular mechanism of cypermethrin neurotoxicity. Obtained results have shown that 2 and 5 μg/ml doses of cypermethrin inhibited glioma U251 cell viability (p<0.05) and increased an oxidative stress level. Contrary, the dose of cypermethrin 1 μg/ml did not induce statistically significant both cell viability and oxidative stress. However, 2 and 5 μg/ml doses of cypermethrin exposure induced cytochrome C release to cytosol in a dose-dependent manner that is a marker of apoptosis initiation. Thus, the neurotoxic effect of pyrethroids can be mediated by the mitochondrial-dependent apoptotic pathway activation via cytochrome C release.

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Rotenone, an environmental toxin, causes abnormal methylation of the mouse brain organoid's genome and ferroptosis

Cited by 18 publications

References 49 publications

Ferroptosis Induced by Pollutants: An Emerging Mechanism in Environmental Toxicology

Ferroptosis Induced by Pollutants: An Emerging Mechanism in Environmental Toxicology

Human-Organoid-Based In Vitro Modeling for Environmental Toxicology

Cypermethrin induces neurotoxicity via inhibition of glial cell viability and apoptosis initiation

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