NRF2 activation inhibits valproic acid-induced neural tube defects in mice

Piorczynski, Ted B.; Lapehn, Samantha; Ringer, Kelsey P.; Allen, Spencer A.; Johnson, Garett A.; Call, Krista; Lucas, S. Marc; Harris, Craig; Hansen, Jason M.

doi:10.1016/j.ntt.2021.107039

Cited by 9 publications

(4 citation statements)

References 94 publications

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“…Nevertheless, a growing body of evidence underscores that a pivotal mechanism contributing to VPA-induced NTDs is the perturbation of redox balance and the subsequent generation of excessive ROS. Emerging research suggests that mitigating redox disruptions could potentially lead to a decline in the prevalence of NTDs [ 16 , 18 , 40 ]. Resveratrol and vitamin E could rescue VPA-induced teratogenicity [41] .…”

Section: Discussionmentioning

confidence: 99%

Melatonin alleviates valproic acid-induced neural tube defects by modulating Src/PI3K/ERK signaling and oxidative stress

Liang,

Wang,

Zhang

et al. 2023

ABBS

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Neural tube defects (NTDs) represent a developmental disorder of the nervous system that can lead to significant disability in children and impose substantial social burdens. Valproic acid (VPA), a widely prescribed first-line antiepileptic drug for epilepsy and various neurological conditions, has been associated with a 4-fold increase in the risk of NTDs when used during pregnancy. Consequently, urgent efforts are required to identify innovative prevention and treatment approaches for VPA-induced NTDs. Studies have demonstrated that the disruption in the delicate balance between cell proliferation and apoptosis is a crucial factor contributing to NTDs induced by VPA. Encouragingly, our current data reveal that melatonin (MT) significantly inhibits apoptosis while promoting the restoration of neuroepithelial cell proliferation impaired by VPA. Moreover, further investigations demonstrate that MT substantially reduces the incidence of neural tube malformations resulted from VPA exposure, primarily by suppressing apoptosis through the modulation of intracellular reactive oxygen species levels. In addition, the Src/PI3K/ERK signaling pathway appears to play a pivotal role in VPA-induced NTDs, with significant inhibition observed in the affected samples. Notably, MT treatment successfully reinstates Src/PI3K/ERK signaling, thereby offering a potential underlying mechanism for the protective effects of MT against VPA-induced NTDs. In summary, our current study substantiates the considerable protective potential of MT in mitigating VPA-triggered NTDs, thereby offering valuable strategies for the clinical management of VPA-related birth defects.

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Section: Discussionmentioning

confidence: 99%

Melatonin alleviates valproic acid-induced neural tube defects by modulating Src/PI3K/ERK signaling and oxidative stress

Liang,

Wang,

Zhang

et al. 2023

ABBS

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“…Methods for redox potential analysis have been previously described by Piorczynski et al [22]. Isolated tissues were collected in 5% perchloric acid and boric acid (0.2 M) containing γ-glutamylglutamate (10 µM, Sigma-Aldrich, St. Louis, MO, USA) for GSH analysis.…”

Section: Glutathione/glutathione Disulfide Redox Potential Analysismentioning

confidence: 99%

Yerba Maté (Ilex paraguariensis) Supplement Exerts Beneficial, Tissue-Specific Effects on Mitochondrial Efficiency and Redox Status in Healthy Adult Mice

Walton,

Saito,

Warren

et al. 2023

Nutrients

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Yerba maté, a herbal tea derived from Ilex paraguariensis, has previously been reported to be protective against obesity-related and other cardiometabolic disorders. Using high-resolution respirometry and reverse-phase high-performance liquid chromatography, the effects of four weeks of yerba maté consumption on mitochondrial efficiency and cellular redox status in skeletal muscle, adipose, and liver, tissues highly relevant to whole-body metabolism, were explored in healthy adult mice. Yerba maté treatment increased the mitochondrial oxygen consumption in adipose but not in the other examined tissues. Yerba maté increased the ATP concentration in skeletal muscle and decreased the ATP concentration in adipose. Combined with the observed changes in oxygen consumption, these data yielded a significantly higher ATP:O2, a measure of mitochondrial efficiency, in muscle and a significantly lower ATP:O2 in adipose, which was consistent with yerba maté-induced weight loss. Yerba maté treatment also altered the hepatic glutathione (GSH)/glutathione disulfide (GSSG) redox potential to a more reduced redox state, suggesting the treatment’s potential protective effects against oxidative stress and for the preservation of cellular function. Together, these data indicate the beneficial, tissue-specific effects of yerba maté supplementation on mitochondrial bioenergetics and redox states in healthy mice that are protective against obesity.

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Section: Introductionmentioning

confidence: 99%

“…The NRF2-mediated antioxidant defense system plays a protective role in some diabetic complications, such as diabetic nephropathy and retinopathy [12,13]. In addition, NRF2 activation could inhibit valproic acid or high glucose-induced NTD in mice [14,15]. Some plant-derived natural compounds have been utilized to protect high glucose-induced NTD, including epigallocatechin gallate, baicalin, quercetin, and curcumin [16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Tripeptide Leu-Pro-Phe from Corn Protein Hydrolysates Attenuates Hyperglycemia-Induced Neural Tube Defect in Chicken Embryos

Yan

Sun

Yu³

et al. 2022

Oxidative Medicine and Cellular Longevity

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Neural tube defect (NTD) is the most common and severe embryopathy causing embryonic malformation and even death associated with gestational diabetes mellitus (GDM). Leu-Pro-Phe (LPF) is an antioxidative tripeptide isolated from hydrolysates of corn protein. However, the biological activity of LPF in vivo and in vitro remains unclear. This study is aimed at investigating the protective effects of tripeptide LPF against NTD in the high glucose exposure condition and delineate the underlying biological mechanism. We found that LPF alleviated NTD in the high glucose-exposed chicken embryo model. In addition, DF-1 chicken embryo fibroblast was loaded with high glucose for induction of oxidative stress and abnormal O-GlcNAcylation in vitro. LPF significantly decreased accumulation of reactive oxygen species and content of malondialdehyde in DF-1 cells but increased the ratio of reduced glutathione and oxidized glutathione in chick embryo. Oxygen radical absorbance capacity results showed that LPF itself had good free radical scavenging capacity and could enhance antioxidant activity of the cell content. Mechanistic studies suggested that the resistance of LPF to oxidative damage may be related to promotion of NRF2 expression and nuclear translocation. LPF alleviated the overall O-GlcNAcylation level of cellular proteins under high glucose conditions and restored the level of Pax3 protein. Collectively, our findings indicate that LPF peptide could act as a nutritional supplement for the protection of development of embryonic neural tube affected by GDM.

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NRF2 activation inhibits valproic acid-induced neural tube defects in mice

Cited by 9 publications

References 94 publications

Melatonin alleviates valproic acid-induced neural tube defects by modulating Src/PI3K/ERK signaling and oxidative stress

Melatonin alleviates valproic acid-induced neural tube defects by modulating Src/PI3K/ERK signaling and oxidative stress

Yerba Maté (Ilex paraguariensis) Supplement Exerts Beneficial, Tissue-Specific Effects on Mitochondrial Efficiency and Redox Status in Healthy Adult Mice

Tripeptide Leu-Pro-Phe from Corn Protein Hydrolysates Attenuates Hyperglycemia-Induced Neural Tube Defect in Chicken Embryos

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