Selenium inhibits ferroptosis and ameliorates autistic-like behaviors of BTBR mice by regulating the Nrf2/GPx4 pathway

Wang, Hongmei; Luan, Yue; Wang, Hongzhi; Zhang, Pengfei; Liu, Sijin; Wang, Peng; Cao, Yonggang; Sun, Hai‐Ying; Wu, Lijie

doi:10.1016/j.brainresbull.2022.02.018

Cited by 53 publications

(33 citation statements)

References 30 publications

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“…Interestingly, a study revealed an unexpected negative correlation between changes in selenium levels following a ketogenic diet and behavioral scores, suggesting that selenium may relate to improving ASD symptoms with the ketogenic diet. Correspondingly, supplementation with selenium inhibits ferroptosis, attenuates ASD-like behaviors, and improves oxidative stress and inflammation through modulation of related gene expression in the BTBR ASD mouse model [ 203 , 204 ]. Clinical trials in ASD should be highly advocated.…”

Section: Mineralsmentioning

confidence: 99%

The Rationale for Vitamin, Mineral, and Cofactor Treatment in the Precision Medical Care of Autism Spectrum Disorder

Indika

Frye²,

Rossignol³

et al. 2023

JPM

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Children with autism spectrum disorder may exhibit nutritional deficiencies due to reduced intake, genetic variants, autoantibodies interfering with vitamin transport, and the accumulation of toxic compounds that consume vitamins. Importantly, vitamins and metal ions are essential for several metabolic pathways and for neurotransmitter functioning. The therapeutic benefits of supplementing vitamins, minerals (Zinc, Magnesium, Molybdenum, and Selenium), and other cofactors (coenzyme Q10, alpha-lipoic acid, and tetrahydrobiopterin) are mediated through their cofactor as well as non-cofactor functions. Interestingly, some vitamins can be safely administered at levels far above the dose typically used to correct the deficiency and exert effects beyond their functional role as enzyme cofactors. Moreover, the interrelationships between these nutrients can be leveraged to obtain synergistic effects using combinations. The present review discusses the current evidence for using vitamins, minerals, and cofactors in autism spectrum disorder, the rationale behind their use, and the prospects for future use.

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Section: Mineralsmentioning

confidence: 99%

The Rationale for Vitamin, Mineral, and Cofactor Treatment in the Precision Medical Care of Autism Spectrum Disorder

Indika

Frye²,

Rossignol³

et al. 2023

JPM

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“…When the intracellular peroxide increases, it will stimulate NRF2 to activate the downstream antioxidant enzymes to inhibit the oxidation reaction. Glutathione peroxidase 4 (GPX4) is also a key factor in the antioxidant system, which converts the lipid peroxide into non-toxic aliphatic alcohol and reduces H 2 O 2 (Shin et al, 2018;Wu et al, 2022).…”

Section: Iron Metabolism Affects the Ferroptosismentioning

confidence: 99%

Recent advances in ferroptosis and therapeutic strategies for glioblastoma

Lü²,

Zhang³

et al. 2023

Front. Mol. Biosci.

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Ferroptosis is an emerging form of cell death characterized by the over-accumulation of iron-dependent lipid peroxidation. Ferroptosis directly or indirectly disturbs glutathione peroxidases cycle through diverse pathways, impacting the cellular antioxidant capacities, aggravating accumulation of reactive oxygen species in lipid, and it finally causes oxidative overload and cell death. Ferroptosis plays a significant role in the pathophysiological processes of many diseases. Glioblastoma is one of the most common primary malignant brain tumors in the central nervous system in adults. Although there are many treatment plans for it, such as surgical resection, radiotherapy, and chemotherapy, they are currently ineffective and the recurrent rate is almost up to 100%. The therapies abovementioned have a strong relationship with ferroptosis at the cellular and molecular level according to the results reported by numerous researchers. The regulation of ferroptosis can significantly determine the outcome of the cells of glioblastoma. Thus ferroptosis, as a regulated form of programed cell death, has the possibility for treating glioblastoma.

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“…15 Further studies have revealed that Se is involved in modulating the synthesis of glutathione peroxidase (GSH-Px) downstream of Nrf2. 16,17 For selenomethionine (Se-Met), it was reported to mitigate intestinal injury caused by zearalenone. 18 However, there are differences in the action mechanisms of distinct toxins, and it is not clear whether Se-Met can rescue DONinduced oxidative stress damage in ISCs.…”

Section: ■ Introductionmentioning

confidence: 99%

“…As an essential nutrient required for the activity of many antioxidant enzymes, dietary selenium (Se) supplementation has the ability to eliminate intracellular lipid peroxidation and inhibit cell apoptosis . Further studies have revealed that Se is involved in modulating the synthesis of glutathione peroxidase (GSH-Px) downstream of Nrf2. , For selenomethionine (Se-Met), it was reported to mitigate intestinal injury caused by zearalenone . However, there are differences in the action mechanisms of distinct toxins, and it is not clear whether Se-Met can rescue DON-induced oxidative stress damage in ISCs.…”

Section: Introductionmentioning

confidence: 99%

Selenomethionine Alleviates DON-Induced Oxidative Stress via Modulating Keap1/Nrf2 Signaling in the Small Intestinal Epithelium

Chen

Liang

Zan

et al. 2022

J. Agric. Food Chem.

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The small intestinal epithelium is regulated in response to various beneficial or harmful environmental information. Deoxynivalenol (DON), a mycotoxin widely distributed in cereal-based feeds, induces oxidative stress damage in the intestine due to the mitochondrial stress. As a functional nutrient, selenomethionine (Se-Met) is involved in synthesizing several antioxidant enzymes, yet whether it can replenish the intestinal epithelium upon DON exposure remains unknown. Therefore, the in vivo model C57BL/6 mice and the in vitro model MODE-K cells were treated with l-Se-Met and DON alone or in combination to confirm the status of intestinal stem cell (ISC)-driven epithelial regeneration. The results showed that 0.1 mg/kg body weight (BW) Se-Met reinstated the growth performance and integrity of jejunal structure and barrier function in DON-challenged mice. Moreover, Lgr5+ ISCs and PCNA+ mitotic cells in crypts were prominently increased by Se-Met in the presence of DON, concomitant with a significant increase in absorptive cells, goblet cells, and Paneth cells. Simultaneously, crypt-derived jejunal organoids from the Se-Met + DON group exhibited more significant growth advantages ex vivo. Furthermore, Se-Met-stimulated Keap1/Nrf2-dependent antioxidant system (T-AOC and GSH-Px) to inhibit the accumulation of ROS and MDA in the jejunum and serum. Moreover, Se-Met failed to rescue the DON-triggered impairment of cell antioxidant function after Nrf2 perturbation using its specific inhibitor ML385 in MODE-K cells. In conclusion, Se-Met protects ISC-driven intestinal epithelial integrity against DON-induced oxidative stress damage by modulating Keap1/Nrf2 signaling.

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Selenium inhibits ferroptosis and ameliorates autistic-like behaviors of BTBR mice by regulating the Nrf2/GPx4 pathway

Cited by 53 publications

References 30 publications

The Rationale for Vitamin, Mineral, and Cofactor Treatment in the Precision Medical Care of Autism Spectrum Disorder

The Rationale for Vitamin, Mineral, and Cofactor Treatment in the Precision Medical Care of Autism Spectrum Disorder

Recent advances in ferroptosis and therapeutic strategies for glioblastoma

Selenomethionine Alleviates DON-Induced Oxidative Stress via Modulating Keap1/Nrf2 Signaling in the Small Intestinal Epithelium

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