Deoxynivalenol induces testicular ferroptosis by regulating the Nrf2/System Xc−/GPX4 axis

Xu, Yang; Huang, Tingyu; Chen, Yunhe; Chen, Fengjuan; Liu, Yu; Wang, Youshuang; Song, Wenxi; Zhang, Juntao; Jiang, Yibao; Wang, Fangyu; Zhang, Cong

doi:10.1016/j.fct.2023.113730

Cited by 19 publications

(6 citation statements)

References 34 publications

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“…Previous studies have found that DON exposure led to liver, kidney, and testicles − damage through inflammation, oxidative stress, apoptosis, iron apoptosis, autophagy, and mitochondrial damage. − To investigate whether HDN has a protective effect on DON-induced liver injury, we first performed in vivo experiments. The results suggested that HDN reduced serum ALT and AST levels and liver coefficients, inhibited hepatocyte swelling, cytoplasmic vacuolation, laxity and hyalinization, hepatocyte nucleus condensation and fragmentation, and other pathohistological changes in the DON group of mice.…”

Section: Discussionmentioning

confidence: 99%

Hesperidin Alleviates Hepatic Injury Caused by Deoxynivalenol Exposure through Activation of mTOR and AKT/GSK3β/TFEB Pathways

Wang,

Chen,

Jiang

et al. 2024

J. Agric. Food Chem.

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Section: Discussionmentioning

confidence: 99%

Hesperidin Alleviates Hepatic Injury Caused by Deoxynivalenol Exposure through Activation of mTOR and AKT/GSK3β/TFEB Pathways

Wang,

Chen,

Jiang

et al. 2024

J. Agric. Food Chem.

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“…138 Yang et al reported that galangin (Gal), derived from Alpinia off icinarum hance and propolis, alleviated myocardial ischemic reperfusioninduced ferroptosis by upregulating the mRNA and protein levels of antioxidant and phase II detoxifying enzymes, especially Nrf2 and GPx4. 139 Additionally, Xiong et al demonstrated that Qi-Shen-Tang (QST), containing a 1:1 composition of Lycium barbarum and Salvia miltiorrhiza, inhibited ferroptosis by targeting the Nrf2/GPx4 signaling pathway, thereby reducing retinitis pigmentosa-induced damage to retinal tissue. 140 Fe 2+ accumulation, ROS formation, MDA production, and inhibition of GSH/GSSG ratio by inhibiting the expression of Nrf2 downstream targets GPx4 and xCT, stimulating the occurrence of ferroptosis thereby inhibiting the growth of tumor cells.…”

Section: Antioxidant Effects Of Fpps On Lpmentioning

confidence: 99%

Recent Advances in the Inhibition of Membrane Lipid Peroxidation by Food-Borne Plant Polyphenols via the Nrf2/GPx4 Pathway

Zhang,

Liu,

et al. 2024

J. Agric. Food Chem.

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Lipid peroxidation (LP) leads to changes in the fluidity and permeability of cell membranes, affecting normal cellular function and potentially triggering apoptosis or necrosis. This process is closely correlated with the onset of many diseases. Evidence suggests that the phenolic hydroxyl groups in food-borne plant polyphenols (FPPs) make them effective antioxidants capable of preventing diseases triggered by cell membrane LP. Proper dietary intake of FPPs can attenuate cellular oxidative stress, especially damage to cell membrane phospholipids, by activating the Nrf2/GPx4 pathway. Nuclear factor E2-related factor 2 (Nrf2) is an oxidative stress antagonist. The signaling pathway regulated by Nrf2 is a defense transduction pathway of the organism against external stimuli such as reactive oxygen species and exogenous chemicals. Glutathione peroxidase 4 (GPx4), under the regulation of Nrf2, is the only enzyme that reduces cell membrane lipid peroxides with specificity, thus playing a pivotal role in regulating cellular ferroptosis and counteracting oxidative stress. This study explored the Nrf2/GPx4 pathway mechanism, antioxidant activity of FPPs, and mechanism of LP. It also highlighted the bioprotective properties of FPPs against LP and its associated mechanisms, including (i) activation of the Nrf2/GPx4 pathway, with GPx4 potentially serving as a central target protein, (ii) regulation of antioxidant enzyme activities, leading to a reduction in the production of ROS and other peroxides, and (iii) antioxidant effects on LP and downstream phospholipid structure. In conclusion, FPPs play a crucial role as natural antioxidants in preventing LP. However, further in-depth analysis of FPPs coregulation of multiple signaling pathways is required, and the combined effects of these mechanisms need further evaluation in experimental models. Human trials could provide valuable insights into new directions for research and application.

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“…In the food chain, zearalenone and deoxynivalenol are mycotoxins that induce male reproductive toxicity. Studies have shown that zearalenone significantly reduces spermatozoal motility and concentration in mice and destroys germ cell organization within the seminiferous tubules, possibly due to an imbalance of the antioxidant system [ 113 , 114 ]. Both mycotoxins increase lipid peroxidation in the testis by downregulating NRF2, SLC7A11, and GPX4 expression.…”

Section: Ferroptosis In Male Reproductive Dysfunctionmentioning

confidence: 99%

Emerging roles of ferroptosis in male reproductive diseases

Yuan,

Sun,

et al. 2023

Cell Death Discov.

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Ferroptosis is a type of programmed cell death mediated by iron-dependent lipid peroxidation that leads to excessive lipid peroxidation in different cells. Ferroptosis is distinct from other forms of cell death and is associated with various diseases. Iron is essential for spermatogenesis and male reproductive function. Therefore, it is not surprising that new evidence supports the role of ferroptosis in testicular injury. Although the molecular mechanism by which ferroptosis induces disease is unknown, several genes and pathways associated with ferroptosis have been linked to testicular dysfunction. In this review, we discuss iron metabolism, ferroptosis, and related regulatory pathways. In addition, we analyze the endogenous and exogenous factors of ferroptosis in terms of iron metabolism and testicular dysfunction, as well as summarize the relationship between ferroptosis and male reproductive dysfunction. Finally, we discuss potential strategies to target ferroptosis for treating male reproductive diseases and provide new directions for preventing male reproductive diseases.

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Deoxynivalenol induces testicular ferroptosis by regulating the Nrf2/System Xc−/GPX4 axis

Cited by 19 publications

References 34 publications

Hesperidin Alleviates Hepatic Injury Caused by Deoxynivalenol Exposure through Activation of mTOR and AKT/GSK3β/TFEB Pathways

Hesperidin Alleviates Hepatic Injury Caused by Deoxynivalenol Exposure through Activation of mTOR and AKT/GSK3β/TFEB Pathways

Recent Advances in the Inhibition of Membrane Lipid Peroxidation by Food-Borne Plant Polyphenols via the Nrf2/GPx4 Pathway

Emerging roles of ferroptosis in male reproductive diseases

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