Environmental toxin chlorpyrifos induces liver injury by activating P53-mediated ferroptosis via GSDMD-mtROS

Feng, Zhiyong; Sheng, Jian; Pei, Hongyan; Sheng, Yongjia; Wang, Jin; Zhou, Xiao‐Nong; Li, Wenyan; Cao, Chenxi; Yang, Yi

doi:10.1016/j.ecoenv.2023.114938

Cited by 11 publications

(6 citation statements)

References 23 publications

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“…By comprehensive analysis, we focused on MDM2, PTGS1, PKCα, and MAPK1 as potentially critical actors linked to Oryza sativa L. indica in the development of AH. MDM2 could bind to p53 and form a complex, then play a key role in the regulation of p53 stability and inducing cell death, and also be involved in liver injury [32,33]. PTGS1 had both cyclooxygenase and peroxidase activities and regulated oxidative stress and inflammation involved in drug-induced liver injury, non-alcoholic fatty liver disease, and other liver diseases [34].…”

Section: Discussionmentioning

confidence: 99%

Oryza sativa L. Indica Seed Coat Ameliorated Concanavalin A—Induced Acute Hepatitis in Mice via MDM2/p53 and PKCα/MAPK1 Signaling Pathways

Zhao,

Li,

Guo

et al. 2023

IJMS

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Acute hepatitis (AH) is a common liver disease with an increasing number of patients each year, requiring the development of new treatments. Hence, our work aimed to evaluate the therapeutic effect of Oryza sativa L. indica (purple rice) seed coat on concanavalin A (ConA)-induced AH and further reveal its potential mechanisms. Purple rice seed coat extract (PRE) was extracted with hydrochloric acid ethanol and analyzed through a widely targeted components method. We evaluated the effects of PRE on AH through histopathological examination, liver function, gut microbiota composition, and the intestinal barrier. The potential targets of PRE on AH were predicted by bioinformatics. Western blotting, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining, and corresponding kits were used to investigate PRE effects on predicting targets and associated signaling pathways in AH mice. In AH model mice, PRE treatment increased transformed mouse 3T3 cell double minute 2 (MDM2) expression to inhibit apoptosis; it also markedly downregulated protein kinase C alpha (PKCα), prostaglandin-endoperoxide synthase 1 (PTGS1), and mitogen-activated protein kinase 1 (MAPK1) activity to alleviate inflammation. Thus, PRE treatment also recovered the intestinal barrier, decreased the lipopolysaccharide (LPS) levels of plasma and the liver, enhanced liver function, and improved the composition of intestinal microbiota. In general, PRE targeting MDM2, PKCα, MAPK1, and PTGS1 ameliorated ConA-induced AH by attenuating inflammation and apoptosis, restoring the intestinal barrier, enhancing the liver function, and improving the gut microbiota, which revealed that the purple rice seed coat might hold possibilities as a therapeutic option for AH.

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Section: Discussionmentioning

confidence: 99%

Oryza sativa L. Indica Seed Coat Ameliorated Concanavalin A—Induced Acute Hepatitis in Mice via MDM2/p53 and PKCα/MAPK1 Signaling Pathways

Zhao,

Li,

Guo

et al. 2023

IJMS

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“…The expression of β- tubulin (1:6000, Servicrbio, anti-mouse, GB12139-100, China) was detected as the reference. The HIF-1α-specific band intensities were normalized using the β -tubulin-specific bands [ 37 ].…”

Section: Methodsmentioning

confidence: 99%

Hypoxia induces pyroptosis and inflammation in the liver of fat greenling (Hexagrammos otakii)

Zhan,

Gao,

Peng

et al. 2024

Comparative Immunology Reports

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“…Chlorpyrifos (CHI), an environmental toxin and pesticide, also induces liver injury through ferroptosis in hepatocytes. 108 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.…”

Section: Airborne Particulate Matter (Pm)mentioning

confidence: 99%

“…The impairment of learning and memory performance was found to be associated with ferroptosis and microglia-mediated neuroinflammation. Chlorpyrifos (CHI), an environmental toxin and pesticide, also induces liver injury through ferroptosis in hepatocytes . CHI promoted ferroptosis in hepatocytes by activating the ferroptosis-promoting protein p53 and disrupting the balances of TFR and ferroportin 1 (FPN-1).…”

Section: Ferroptosis Inducers In Environmental Pollutantsmentioning

confidence: 99%

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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Environmental toxin chlorpyrifos induces liver injury by activating P53-mediated ferroptosis via GSDMD-mtROS

Cited by 11 publications

References 23 publications

Oryza sativa L. Indica Seed Coat Ameliorated Concanavalin A—Induced Acute Hepatitis in Mice via MDM2/p53 and PKCα/MAPK1 Signaling Pathways

Oryza sativa L. Indica Seed Coat Ameliorated Concanavalin A—Induced Acute Hepatitis in Mice via MDM2/p53 and PKCα/MAPK1 Signaling Pathways

Hypoxia induces pyroptosis and inflammation in the liver of fat greenling (Hexagrammos otakii)

Ferroptosis Induced by Pollutants: An Emerging Mechanism in Environmental Toxicology

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