Ferroptosis is critical for phthalates driving the blood-testis barrier dysfunction via targeting transferrin receptor

Redox Biology, Journal Year: 2022, Volume and Issue: 59, P. 102584 - 102584

Published: Dec. 22, 2022

The global rate of human male infertility is rising at an alarming owing to environmental and lifestyle changes. Phthalates are the most hazardous chemical additives in plastics have apparently negative impact on function reproductive system. Ferroptosis a recently described form iron-dependent cell death has been linked several diseases. Transferrin receptor (TfRC), specific ferroptosis marker, universal iron importer for all cells using extracellular transferrin. We aim investigate potential involvement during toxicity, provide means drawing conclusions effect phthalates-induced disease. In this study, we found that di (2-ethylhexyl) phthalate (DEHP) triggered blood-testis barrier (BTB) dysfunction mouse testicular tissues. DEHP also induced mitochondrial morphological changes lipid peroxidation, which manifestations ferroptosis. As primary metabolite DEHP, mono-2-ethylhexyl (MEHP) by inhibiting glutathione defense network increasing peroxidation. TfRC knockdown blocked MEHP-induced decreasing intracellular levels Fe2+. Our findings indicate can regulate Sertoli therefore novel therapeutic molecule disorders patients with infertility.

Language: Английский

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Lycopene prevents Di-(2-ethylhexyl) phthalate-induced mitophagy and oxidative stress in mice heart via modulating mitochondrial homeostasis

The Journal of Nutritional Biochemistry, Journal Year: 2023, Volume and Issue: 115, P. 109285 - 109285

Published: Feb. 14, 2023

Language: Английский

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Phthalates Induce Neurotoxicity by Disrupting the Mfn2-PERK Axis-Mediated Endoplasmic Reticulum–Mitochondria Interaction

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(13), P. 7411 - 7422

Published: Feb. 23, 2024

Di-(2-ethylhexyl) phthalate (DEHP), as the most common phthalate, has been extensively used a plasticizer to improve plasticity of agricultural products, which pose severe harm human health. Mitochondrial dynamics and endoplasmic reticulum (ER) homeostasis are indispensable for maintaining mitochondria-associated ER membrane (MAM) integrity. In this study, we aimed explore effect DEHP on nervous system its association with ER-mitochondria interaction. Here, showed that caused morphological changes, motor deficits, cognitive impairments, blood-brain barrier disruption in brain. triggered stress, is mainly mediated by protein kinase R-like (PERK) signaling. Moreover, DEHP-induced mitofusin-2 (Mfn2) downregulation results imbalance mitochondrial dynamics. Interestingly, exposure impaired MAMs inhibiting Mfn2-PERK Above all, study elucidates axis-mediated interaction phthalate-induced neurotoxicity could be potentially developed novel therapy neurological diseases.

Language: Английский

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Phthalates (PAEs) and reproductive toxicity: Hypothalamic-pituitary-gonadal (HPG) axis aspects

Journal of Hazardous Materials, Journal Year: 2023, Volume and Issue: 459, P. 132182 - 132182

Published: July 28, 2023

Language: Английский

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Co-exposure to molybdenum and cadmium evokes necroptosis and decreases apoptosis in duck myocardium

The Science of The Total Environment, Journal Year: 2023, Volume and Issue: 902, P. 166074 - 166074

Published: Aug. 6, 2023

Language: Английский

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Cannabidiol alleviates perfluorooctane sulfonate-induced macrophage extracellular trap mediate inflammation and fibrosis in mice liver

Ecotoxicology and Environmental Safety, Journal Year: 2023, Volume and Issue: 263, P. 115374 - 115374

Published: Aug. 14, 2023

As a new type of persistent organic pollutant, perfluorooctane sulphonate (PFOS) has received extensive attention worldwide. Cannabidiol (CBD) is non-psychoactive natural cannabinoid extract that been proved to have antioxidation, regulation inflammation and other functions. However, the effects PFOS on liver injury whether CBD can alleviate PFOS-induced are still unclear. Therefore, in this study, we used (10 mg/kg) and/or (5 intraperitoneally inject mice for 30 days. We found exposure led inflammatory infiltration mice, increased formation macrophage extracellular trap (MET), promoted fibrosis. In vitro, established coculture system RAW264.7, AML12 LX-2 cells, treated them with μM) (200 μM). The results showed could also induce expression MET, fibrosis marker genes vitro. Coiled-coil domain containing protein 25 (CCD25), as MET-DNA sensor, was investigate its ability regulate fibrosis, knocked down CCDC25 downstream proteins (integrin-linked kinase, ILK) by siRNA technology, QNZ inhibit NF-κB pathway. knockdown ILK inhibition pathway MET-induced gene expression. summary, MET promote through CCDC25-ILK-NF-κB signaling axis, while treatment protective effect, it Macromolecular docking effect achieved combining peptidylarginine deiminase 4 (PAD4) release MET. regulating axis an innovative option effectively reduce hepatotoxicity. Our study reveals mechanism hepatotoxicity provides promising insights into role process.

Language: Английский

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AQP1 Deficiency Drives Phthalate-Induced Epithelial Barrier Disruption through Intestinal Inflammation

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(27), P. 15334 - 15344

Published: June 25, 2024

Di-2-ethylhexyl phthalate (DEHP) is frequently used as a plasticizer to enhance the plasticity and durability of agricultural products, which pose adverse effects human health environment. Aquaporin 1 (AQP1) main water transport channel protein involved in maintenance intestinal integrity. However, impact DEHP exposure on gut its potential mechanisms remain elusive. Here, we determined that induced compromised duodenum structure, was concomitant with mitochondrial structural injury epithelial cells. Importantly, caused inflammatory cell damage strong response accompanied by activating TLR4/MyD88/NF-κB signaling pathway. Mechanistically, directly inhibits expression AQP1 thus leads an response, ultimately disrupting integrity barrier function. Collectively, our findings uncover role phthalate-induced disorders, could be promising therapeutic approach for treating patients disorders or diseases.

Language: Английский

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Hepatotoxic effects of chronic exposure to environmentally relevant concentrations of Di-(2-ethylhexyl) phthalate (DEHP) on crucian carp: Insights from multi-omics analyses

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 923, P. 171447 - 171447

Published: March 4, 2024

Language: Английский

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The FAK/occludin/ZO-1 complex is critical for cadmium-induced testicular damage by disruption of the integrity of the blood-testis barrier in chickens

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 470, P. 134126 - 134126

Published: March 26, 2024

Language: Английский

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SLC7A11 as a therapeutic target to attenuate phthalates-driven testosterone level decline in mice

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: May 1, 2024

Phthalates exposure is a major public health concern due to the accumulation in environment and associated with levels of testosterone reduction, leading adverse pregnancy outcomes. However, relationship between phthalate-induced level decline ferroptosis remains poorly defined.

Language: Английский

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