Phthalate-induced testosterone/androgen receptor pathway disorder on spermatogenesis and antagonism of lycopene

Zhao, Yi; Li, Xue-Nan; Zhang, Hao; Cui, Jia-Gen; Wang, Jiaxin; Chen, Ming-Shan; Li, Jinlong

doi:10.1016/j.jhazmat.2022.129689

Cited by 73 publications

(34 citation statements)

References 86 publications

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“…11 Consuming lycopene in the form of fresh tomatoes, tomato-based products, and supplements can decrease the risk of cardiovascular disease. 12 Antioxidant properties of lycopene may contribute to the improvement of bone quality, as well as to the prevention of obesity-induced osteoporosis. 13 LYC inhibits MAPK and nuclear factor kappa-B (NF-κB) pathways and attenuates renal and hepatic inflammatory responses.…”

Section: Introductionmentioning

confidence: 99%

“…Among the carotenoids, lycopene (LYC) is considered a powerful antioxidant, significantly more powerful than α-tocopherol (10× added potent) or β-carotene (twice as potent) . Consuming lycopene in the form of fresh tomatoes, tomato-based products, and supplements can decrease the risk of cardiovascular disease . Antioxidant properties of lycopene may contribute to the improvement of bone quality, as well as to the prevention of obesity-induced osteoporosis .…”

Section: Introductionmentioning

confidence: 99%

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Lycopene Attenuates Di(2-ethylhexyl) Phthalate-Induced Mitochondrial Damage and Inflammation in Kidney via cGAS–STING Signaling

Dai

Zhao

et al. 2022

J. Agric. Food Chem.

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Di(2-ethylhexyl) phthalate (DEHP) is a highly harmful and persistent environmental pollutant. Due to its unique chemical composition, it frequently dissolves and enters the environment to endanger human and animal health. Lycopene is a natural bioactive component that can potentially reduce the risk of environmental factor-induced chronic diseases. The present study sought to explore the role and underlying mechanism of lycopene (LYC) on DEHP-induced renal inflammatory response and apoptosis. In this study, mice were orally treated with LYC (5 mg/kg BW/day) and/or DEHP (500 or 1000 mg/kg BW/day) for 28 days. Our results indicated that LYC prevented DEHP-induced histopathological alterations and ultrastructural injuries, including decreased mitochondrial membrane potential (ΔΨm), PINK1/Parkin pathway-mediated mitophagy, and mitochondrial energetic deficit. When damaged mitochondria release mitochondrial DNA (mtDNA) into cytosol, LYC can alleviate inflammation and apoptosis caused by DEHP exposure by activating the cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS–STING) signal pathway. Collectively, our data demonstrate that LYC can reduce mitophagy caused by DEHP exposure by activating the PINK1/Parkin pathway and then reduce renal inflammation and apoptosis through the cGAS–STING pathway.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lycopene Attenuates Di(2-ethylhexyl) Phthalate-Induced Mitochondrial Damage and Inflammation in Kidney via cGAS–STING Signaling

Dai

Zhao

et al. 2022

J. Agric. Food Chem.

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“…DEHP (200 mg/kg/d) causes DNA damage in sperm and has detrimental effects on the reproductive system from the prepubertal to the pubertal period [ 25 ]. DEHP (500 mg/kg/d) induces spermatogenesis disorder by inhibiting testosterone/androgen receptor pathway [ 26 ]. The DEHP in soil (1–264 mg/kg) or sewage sludge (12–1250 mg/kg) is difficult to degrade and thus persist in the environment [ 27 ].…”

Section: Methodsmentioning

confidence: 99%

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

Zhao¹,

Zhang²,

Cui³

et al. 2023

Redox Biology

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“…32 It is confirmed that the lowest observed adverse effect level (LOAEL) of DEHP in mice was 140 mg/kg BW/day, and research proved that decreasing placental weight could significantly be observed in DEHP (500 mg/kg BW/day) exposure. 8,33,34 Kidney Histology Observation. The renal sample was preserved in 10% neutral buffer formalin and turned into paraffin.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Novel Role of Hemeoxygenase-1 in Phthalate-Induced Renal Proximal Tubule Cell Ferroptosis

Chen

Wang

Zhang

et al. 2023

J. Agric. Food Chem.

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Phthalates are widely used to improve the flexibility of poly(vinyl chloride) (PVC) polymer agriculture products. Di(2-ethylhexyl) phthalate (DEHP) is a type of addition to plastic and can lead to many health problems. Hemeoxygenase-1 (HO-1) is an extremely important molecule that releases enzymatic products to promote ferroptosis. This research aimed to explore the function of HO-1 in DEHP-induced renal proximal tubule cell ferroptosis. In the experiment, ICR male mice are exposed to (0, 50, 200, and 500 mg/kg BW/day) DEHP for 28 days. Here, we observed that DEHP induced glomeruli atrophy and the tubules swell. Furthermore, DEHP exposure could increase ferrous iron content and decrease antioxidant activity. We also found that DEHP exposure increased the expression of nuclear factor-erythroid 2 p45-related factor 2 (NFE2L2) in the nucleus. In particular, the expression of (HO-1) is significantly increased both in protein and mRNA levels. Glutathione peroxidase 4 (GPX4) as an endogenous control of ferroptosis was downregulated, which proved the occurrence of ferroptosis. In the study, exposure to DEHP activated the NFE2L2/HO-1 signaling pathway and resulted in ferroptosis of the proximal tubule. This research connects ferroptosis with HO-1, providing new insights into the potential roles of phthalates in nephrotoxicity.

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Phthalate-induced testosterone/androgen receptor pathway disorder on spermatogenesis and antagonism of lycopene

Cited by 73 publications

References 86 publications

Lycopene Attenuates Di(2-ethylhexyl) Phthalate-Induced Mitochondrial Damage and Inflammation in Kidney via cGAS–STING Signaling

Lycopene Attenuates Di(2-ethylhexyl) Phthalate-Induced Mitochondrial Damage and Inflammation in Kidney via cGAS–STING Signaling

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

Novel Role of Hemeoxygenase-1 in Phthalate-Induced Renal Proximal Tubule Cell Ferroptosis

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