Toxic effects of arsenic trioxide on spermatogonia are associated with oxidative stress, mitochondrial dysfunction, autophagy and metabolomic alterations

Chen, Hanming; Liu, Gaoyang; Qiao, Na; Kang, Zhenlong; Hu, Lianmei; Liao, Jianzhao; Yang, Fan; Pang, Congying; Liu, Bingxian; Zeng, Qiwen; Li, Yao; Liu, Ying

doi:10.1016/j.ecoenv.2019.110063

Cited by 45 publications

(13 citation statements)

References 55 publications

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“…To identify novel mechanism of ATO action in NB cells, we investigated the changes in the proteome after ATO treatment in SK-N-BE (2) cells. It had been reported that ATO induced ROS production [21], and in the present study we identi ed a group of proteins related to ferroptosis and ferritinophagy, such as GPX4, ferritin (FTL, FTH1), LC3, P62, ATG7 and NCOA4.…”

Section: Discussionmentioning

confidence: 53%

“…Since then, dozens of studies showed the broad-spectrum anti-tumor activities of . One of the interesting ndings was that ATO increasing the levels of malonaldehyde (MDA) and reactive oxygen species (ROS), while decreasing glutathione (GSH); The accumulation of ROS could trigger oxidative stress and damage mitochondrial membrane potential in spermatogonia [21]and pulmonary broblast cell [22], therefore activate downstream caspase-dependent apoptosis pathways [23];this allowed ATO to be inferred can treat cancer effectively through this mechanism. Our previous studies con rmed the anti-tumor growth effect of ATO in NB cells.…”

Section: Introductionmentioning

confidence: 99%

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Arsenic Trioxide Increases Apoptosis of SK-N-BE (2) Cells Partially by Inducing GPX4-mediated Ferroptosis

Feng

Chen

et al. 2022

Preprint

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Neuroblastoma (NB) is the most common extracranial tumor in central nervous system threatening children’s health with limited therapeutic options. Arsenic trioxide (ATO) has been identified the cytotoxicity in NB cells but the potential mechanism remains unclear. In this study, we attempted to obtain some insight into the mechanisms of cell death induced by ATO in NB cells using proteomic technology. Proteomic analyses found that ATO can affect the signaling pathway associated with ferroptosis, including the upregulation of iron absorption (FTL, FTH1, HO-1), ferritinophagy (LC3, P62, ATG7, NCOA4) and modifier of glutathione synthesis (GCLM); downregulation of glutamine synthetase (GS) and GPX4, which was the critical inhibitor of ferroptosis. Western blot analysis revealing GPX4 expression in SK-N-BE (2) cells decreased after treatment with ATO (7.3 μM), resulting in a loss of GPX4 activity. Our study revealed that ATO may induce ferroptosis in neuroblastoma cell SK-N-BE (2) by facilitating the downregulation of GPX4, ultimately resulting in iron-dependent oxidative death.

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Section: Discussionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Arsenic Trioxide Increases Apoptosis of SK-N-BE (2) Cells Partially by Inducing GPX4-mediated Ferroptosis

Feng

Chen

et al. 2022

Preprint

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“…Due to the high oxygen consumption of renal tissues in normal physiological function to complete the active transport, and reabsorption of water or electrolytes, the accumulation of oxygen free radicals and the imbalance of antioxidants can easily lead to renal tissue damage [47]. It has been shown that As reduce antioxidant defenses by increasing lipid peroxidation [48]. These results suggested that the antioxidant capacity of the carp head kidney may be affected under As exposure.…”

Section: Discussionmentioning

confidence: 99%

Zinc Alleviates Arsenic-Induced Inflammation and Apoptosis in the Head Kidney of Common Carp by Inhibiting Oxidative Stress and Endoplasmic Reticulum Stress

Xing

Zhang

Chi

2021

Biol Trace Elem Res

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Arsenic (As) pollution is ubiquitous in water, which shows immunotoxicity to aquatic organisms. As an indispensable regulator of gene transcription and enzymatic modification, zinc (Zn) may play a preventive and therapeutic effect on As toxicity. The purpose of this study was to investigate the interactions of As and Zn on the head kidney of common carp Cyprinus carpio. Herein the carp were treated alone or in combination with waterborne As 3+ (2.83 mg/L) and/or Zn 2+ (1 mg/L). Results suggested a head kidney-toxic effect of As exposure, which was manifested by the histopathological damage of the head kidney, elevation of nuclear translocation of pro-inflammatory nuclear factor-kappa light chain enhancer of B cells (NF-κB), and blockage of the anti-oxidative nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. The global activation of three endoplasmic reticulum (ER) stress pathways led to the execution of programmed cell death, including ER apoptosis mediated by C/EBP-homologous protein (CHOP), death receptor-mediated exogenous cell apoptosis, and the endogenous apoptosis executed by Caspases9. The combined application of Zn can significantly improve the histopathological damage of the head kidney, the imbalance of the antioxidant system, and the apoptosis outcomes due to ER stress. In conclusion, this study indicates that Zn has an antagonistic effect on the head kidney injury of common carp induced by sub-chronic As exposure. The results of this study provide basic data for the risk assessment of As accumulation in an aquatic environment and a reference for the use of Zn preparation in aquaculture.

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“…Plants are constantly exposed to metal stress. This has become the most serious environmental constraint that affects plant growth and development [ 1 , 2 , 3 ]. Among heavy metals, arsenic (As) is a dangerous contaminant with no known biological function in plants and has higher solubility in water.…”

Section: Introductionmentioning

confidence: 99%

Exogenously-Sourced Salicylic Acid Imparts Resilience towards Arsenic Stress by Modulating Photosynthesis, Antioxidant Potential and Arsenic Sequestration in Brassica napus Plants

et al. 2022

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In the current study, salicylic acid (SA) assesses the physiological and biochemical responses in overcoming the potential deleterious impacts of arsenic (As) on Brassica napus cultivar Neelam. The toxicity caused by As significantly reduced the observed growth and photosynthetic attributes and accelerated the reactive oxygen species (ROS). Plants subjected to As stress revealed a significant (p ≤ 0.05) reduction in the plant growth and photosynthetic parameters, which accounts for decreased carbon (C) and sulfur (S) assimilation. Foliar spray of SA lowered the oxidative burden in terms of hydrogen peroxide (H2O2), superoxide anion (O2•−), and lipid peroxidation in As-affected plants. Application of SA in two levels (250 and 500 mM) protected the Brassica napus cultivar from As stress by enhancing the antioxidant capacity of the plant by lowering oxidative stress. Among the two doses, 500 mM SA was most effective in mitigating the adverse effects of As on the Brassica napus cultivar. It was found that SA application to the Brassica napus cultivar alleviated the stress by lowering the accumulation of As in roots and leaves due to the participation of metal chelators like phytochelatins, enhancing the S-assimilatory pathway, carbohydrate metabolism, higher cell viability in roots, activity of ribulose 1, 5-bisphosphate carboxylase (Rubisco), and proline metabolism through the active participation of γ-glutamyl kinase (GK) and proline oxidase (PROX) enzyme. The current study shows that SA has the capability to enhance the growth and productivity of B. napus plants cultivated in agricultural soil polluted with As and perhaps other heavy metals.

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Toxic effects of arsenic trioxide on spermatogonia are associated with oxidative stress, mitochondrial dysfunction, autophagy and metabolomic alterations

Cited by 45 publications

References 55 publications

Arsenic Trioxide Increases Apoptosis of SK-N-BE (2) Cells Partially by Inducing GPX4-mediated Ferroptosis

Arsenic Trioxide Increases Apoptosis of SK-N-BE (2) Cells Partially by Inducing GPX4-mediated Ferroptosis

Zinc Alleviates Arsenic-Induced Inflammation and Apoptosis in the Head Kidney of Common Carp by Inhibiting Oxidative Stress and Endoplasmic Reticulum Stress

Exogenously-Sourced Salicylic Acid Imparts Resilience towards Arsenic Stress by Modulating Photosynthesis, Antioxidant Potential and Arsenic Sequestration in Brassica napus Plants

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