The molecular mechanism underlining the preventive effect of vitamin D against hepatic and renal acute toxicity through the NrF2/ BACH1/ HO-1 pathway

El-Magd, Nada F. Abo; Eraky, Salma M.

doi:10.1016/j.lfs.2020.117331

Cited by 34 publications

(28 citation statements)

References 45 publications

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“…Meanwhile, calcitriol also triggered Nrf2 signaling, inducing the expression of targeted genes and protecting the brain from excessive oxidative stress. In support of our ndings, recent studies also illustrate a pivotal role of Nrf2 in the protective effects of VitD in Alzheimer's disease, lung injury, skin aging, liver failure and kidney toxicity (21)(22)(23)(24)(25). Given that Keap-1 is targeted to autophagosomes for degradation, the reduction of Keap-1 expression and the decreased co-expression of p62 and Keap1 following calcitriol treatment suggest that Nrf2 might be activated by VitD through autophagy mediated by the interaction between p62 and Keap1.…”

Section: Discussionsupporting

confidence: 72%

Vitamin D confers neuroprotective effects in traumatic brain injury by activating Nrf2 signaling through an autophagy-mediated mechanism

Wang

Jin

Yang

et al. 2021

Preprint

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Background: Traumatic brain injury (TBI) initiates an oxidative cascade that contributes to the delayed progressive damage, whereas autophagy is critical in maintaining homeostasis during stressful challenge. We previously demonstrated that vitamin D (VitD) shows strong neuroprotective and anti-oxidative properties in the animal models of TBI. Therefore, the present study aimed to further explore the potential interrelationship between oxidative stress and autophagy in the progression of TBI and therapeutic mechanism of VitD. Methods: Neuroprotective effects of calcitriol, the active form of VitD, were examined following TBI. We further evaluated the impacts of TBI and VitD treatment on autophagic process and nuclear factor E2-related factor 2 (Nrf2) signaling. To confirm the mechanism, chloroquine (CQ) treatment and Nrf2−/− mice were used to block autophagy and Nrf2 pathway, respectively. Results: We found that treatment of calcitriol markedly ameliorated the neurological deficits and histopathological changes following TBI. The brain damage impaired autophagic flux and impeded Nrf2 signaling, the major regulator in antioxidant response, consequently leading to uncontrolled and excessive oxidative stress. Meanwhile, calcitriol promoted autophagic process and activated Nrf2 signaling as evidenced by the reduced Keap1 expression and enhanced Nrf2 translocation, thereby mitigating TBI-induced oxidative damage. To further confirm whether autophagy was responsible for Keap1 degradation and Nrf2 activation, the lysosomal inhibitor, CQ, was used to block autophagy. Our data suggested that CQ treatment abrogated calcitriol-induced autophagy and compromised Nrf2 activation with increased Keap1 accumulation and reduced expression of Nrf2-targeted genes. Additionally, both CQ treatment and Nrf2 genetic knockout abolished the protective effects of VitD against both TBI-induced neurological deficits and neuronal apoptosis. Conclusions: Therefore, our work demonstrated a neuroprotective role of VitD in TBI by triggering Nrf2 activation, which might be mediated by autophagy.

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Section: Discussionsupporting

confidence: 72%

Vitamin D confers neuroprotective effects in traumatic brain injury by activating Nrf2 signaling through an autophagy-mediated mechanism

Wang

Jin

Yang

et al. 2021

Preprint

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“…The previous study shows that the Nrf2 signaling pathway is an important antioxidant response pathway, and it has been proven to be activated by vitamin D to reduce the inflammation reaction. 23 The binding of active vitamin D to VDR, interaction with retinoid X receptor (RXR), and then binding to the vitamin D response element (VDRE) can activate many vitamin D-sensitive target genes, including Nrf2. 43 Chen et al found that the VDR has the ability to physically bind the Nrf2 promoter using a ChIP approach.…”

Section: Discussionmentioning

confidence: 99%

“…22 Vitamin D can activate the Nrf2/HO-1 pathway to ameliorate liver and kidney injuries, which are markedly promoted by oxidative stress and inflammation. 23 Because ED-71 is an analog of active vitamin D, it is hypothesized that ED-71 may have a similar effect on other inflammatory diseases, including periodontitis.…”

Section: Introductionmentioning

confidence: 99%

<p>Eldecalcitol Inhibits LPS-Induced NLRP3 Inflammasome-Dependent Pyroptosis in Human Gingival Fibroblasts by Activating the Nrf2/HO-1 Signaling Pathway</p>

Huang¹,

Zhang²,

Yang³

et al. 2020

DDDT

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“…Vitamin D was reported to protect against drug-induced kidney and liver injury (96). Similarly, BaSalamah et al (97) reported that vitamin D alleviated kidney infl ammation and protected kidney.…”

Section: Vitamin D and Kidney Diseasesmentioning

confidence: 97%

Vitamin D may protect against multiple organ damage caused by COVID-19

Aygün¹

2020

BLL

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The molecular mechanism underlining the preventive effect of vitamin D against hepatic and renal acute toxicity through the NrF2/ BACH1/ HO-1 pathway

Cited by 34 publications

References 45 publications

Vitamin D confers neuroprotective effects in traumatic brain injury by activating Nrf2 signaling through an autophagy-mediated mechanism

Vitamin D confers neuroprotective effects in traumatic brain injury by activating Nrf2 signaling through an autophagy-mediated mechanism

<p>Eldecalcitol Inhibits LPS-Induced NLRP3 Inflammasome-Dependent Pyroptosis in Human Gingival Fibroblasts by Activating the Nrf2/HO-1 Signaling Pathway</p>

Vitamin D may protect against multiple organ damage caused by COVID-19

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