Protective Effect of Vitamin D3 Against Pb-Induced Neurotoxicity by Regulating the Nrf2 and NF-κB Pathways

Hosseinirad, Hossein; Shahrestanaki, Jahan Keivanlou; Moghaddam, Mehrdad Moosazadeh; Mousazadeh, Amirreza; Yadegari, Pouya; Afsharzadeh, Nousha

doi:10.1007/s12640-020-00322-w

Cited by 24 publications

(6 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a model of lead-induced neurotoxicity and oxidative stress, decreases in anti-oxidant molecules GSH, SOD and catalase and increased ROS production are observed in rat cortex. Cholecalciferol reversed these changes possibly via Nrf2 and/or NF-κB mechanism [ 150 ]. In a model of experimentally induced epilepsy in young male rats, cholecalciferol not only reduced seizure severity, but corrected associated memory deficits, reduced extracellular calcium, restored anti-oxidative enzymes SOD and glutathione-related enzymes and reduced inflammatory cytokine production in the hippocampus [ 151 ].…”

Section: Vitamin D Is Neuroprotective In Neurons and Adult Brainmentioning

confidence: 99%

Vitamin D and the Central Nervous System: Causative and Preventative Mechanisms in Brain Disorders

Cui

Eyles

2022

Nutrients

View full text Add to dashboard Cite

Twenty of the last one hundred years of vitamin D research have involved investigations of the brain as a target organ for this hormone. Our group was one of the first to investigate brain outcomes resulting from primarily restricting dietary vitamin D during brain development. With the advent of new molecular and neurochemical techniques in neuroscience, there has been increasing interest in the potential neuroprotective actions of vitamin D in response to a variety of adverse exposures and how this hormone could affect brain development and function. Rather than provide an exhaustive summary of this data and a listing of neurological or psychiatric conditions that vitamin D deficiency has been associated with, here, we provide an update on the actions of this vitamin in the brain and cellular processes vitamin D may be targeting in psychiatry and neurology.

show abstract

Section: Vitamin D Is Neuroprotective In Neurons and Adult Brainmentioning

confidence: 99%

Vitamin D and the Central Nervous System: Causative and Preventative Mechanisms in Brain Disorders

Cui

Eyles

2022

Nutrients

View full text Add to dashboard Cite

show abstract

“…Three reports are in concordance with our findings. Oxidative stress occurred with increased MDA and decreased GSH in the livers of chlorpyrifos-treated common carps [ 49 ], as well as in the cerebral cortex of Pb-treated rats [ 36 ]. Pancreatic oxidative stress occurred in bisphenol A-exposed chickens with up-regulated MDA and down-regulated GSH and TAC [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Se Alleviated Pb-Caused Neurotoxicity in Chickens: SPS2-GPx1-GSH-IL-2/IL-17-NO Pathway, Selenoprotein Suppression, Oxidative Stress, and Inflammatory Injury

Li,

Liang,

Jiang

et al. 2024

Antioxidants

View full text Add to dashboard Cite

Lead (Pb), a heavy metal environmental pollutant, poses a threat to the health of humans and birds. Inflammation is one of the most common pathological phenomena in the case of illness and poisoning. However, the underlying mechanisms of inflammation remain unclear. The cerebellum and the thalamus are important parts of the nervous system. To date, there have been no reports of Pb inducing inflammation in animal cerebellums or thalami. Selenium (Se) can relieve Pb poisoning. Therefore, we aimed to explore the mechanism by which Se alleviates Pb toxicity to the cerebellums and thalami of chickens by establishing a chicken Pb or/and Se treatment model. Our results demonstrated that exposure to Pb caused inflammatory damage in cerebellums and thalami, evidenced by the characteristics of inflammation, the decrease in anti-inflammatory factors (interleukin (IL)-2 and interferon-γ (INF-γ)), and the increase in pro-inflammatory factors (IL-4, IL-6, IL-12β, IL-17, and nitric oxide (NO)). Moreover, we found that the IL-2/IL-17–NO pathway took part in Pb-caused inflammatory injury. The above findings were reversed by the supplementation of dietary Se, meaning that Se relieved inflammatory damage caused by Pb via the IL-2/IL-17–NO pathway. In addition, an up-regulated oxidative index malondialdehyde (MDA) and two down-regulated antioxidant indices (glutathione (GSH) and total antioxidant capacity (TAC)) were recorded after the chickens received Pb stimulation, indicating that excess Pb caused an oxidant/antioxidant imbalance and oxidative stress, and the oxidative stress mediated inflammatory damage via the GSH–IL-2 axis. Interestingly, exposure to Pb inhibited four glutathione peroxidase (GPx) family members (GPx1, GPx2, GPx3, and GPx4), three deiodinase (Dio) family members (Dio1, Dio2, and Dio3), and fifteen other selenoproteins (selenophosphate synthetase 2 (SPS2), selenoprotein (Sel)H, SelI, SelK, SelM, SelO, SelP1, SelPb, SelS, SelT, SelU, and selenoprotein (Sep)n1, Sepw1, Sepx1, and Sep15), suggesting that Pb reduced antioxidant capacity and resulted in oxidative stress involving the SPS2–GPx1–GSH pathway. Se supplementation, as expected, reversed the changes mentioned above, indicating that Se supplementation improved antioxidant capacity and mitigated oxidative stress in chickens. For the first time, we discovered that the SPS2–GPx1–GSH–IL-2/IL-17–NO pathway is involved in the complex inflammatory damage mechanism caused by Pb in chickens. In conclusion, this study demonstrated that Se relieved Pb-induced oxidative stress and inflammatory damage via the SPS2–GPx1–GSH–IL-2/IL-17–NO pathway in the chicken nervous system. This study offers novel insights into environmental pollutant-caused animal poisoning and provides a novel theoretical basis for the detoxification effect of Se against oxidative stress and inflammation caused by toxic pollutants.

show abstract

“…Nrf2 signaling is an important endogenous antioxidant stress pathway, which is deficient and insufficient for antioxidant response in BPH [ 11 , 12 ]. According to many studies, vitamin D could raise Nrf2 expression and activate Nrf2 signaling to reduce oxidative stress in human diseases [ 26 – 28 ]. The present study revealed that 25-OH D was able to alleviate prostate cell oxidative stress by triggering Nrf2 signaling, which indicated a potential antioxidative stress role of 25-OH D in the process of BPH.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effects of 25-Hydroxyvitamin D on the Pathological Process of Benign Prostatic Hyperplasia: An In Vitro Evidence

Chen

Liu

et al. 2021

Disease Markers

View full text Add to dashboard Cite

The pathogenesis of benign prostatic hyperplasia (BPH) is extremely complicated which involving the multiple signaling pathways. The deficiency of vitamin D is an important risk factor for BPH, and exogenous vitamin D is effective for the treatment of BPH. In this study, we provided in vitro mechanical evidence of vitamin D as a treatment for BPH using BPH-1, WPMY-1, and PBMC cells. We found that 25-hydroxyvitamin D (25-OH D) level is decreased in BPH and closely correlated with age, prostate volume, maximum flow, international prostate symptom score, and prostate-specific antigen of the BPH patients. We further revealed that 25-OH D ameliorated TGF-β1 induces epithelial-mesenchymal transition (EMT) of BPH-1 cells and proliferation of WPMY-1 cells via blocking TGF-β signaling. Moreover, 25-OH D was able to block NF-κB signaling in PBMCs of BPH patients and STAT3 signaling in BPH cells to relieve inflammation. 25-OH D also protects BPH cells from inflammatory cytokines selected by PBMCs. Finally, we uncovered that 25-OH D alleviated prostate cell oxidative stress by triggering Nrf2 signaling. In conclusion, our data verified that 25-OH D regulated multiple singling pathways to restrain prostate cell EMT, proliferation, inflammation, and oxidative stress. Our study provides in vitro mechanical evidence to support clinical use of vitamin D as a treatment for BPH.

show abstract

Protective Effect of Vitamin D3 Against Pb-Induced Neurotoxicity by Regulating the Nrf2 and NF-κB Pathways

Cited by 24 publications

References 42 publications

Vitamin D and the Central Nervous System: Causative and Preventative Mechanisms in Brain Disorders

Vitamin D and the Central Nervous System: Causative and Preventative Mechanisms in Brain Disorders

Se Alleviated Pb-Caused Neurotoxicity in Chickens: SPS2-GPx1-GSH-IL-2/IL-17-NO Pathway, Selenoprotein Suppression, Oxidative Stress, and Inflammatory Injury

Therapeutic Effects of 25-Hydroxyvitamin D on the Pathological Process of Benign Prostatic Hyperplasia: An In Vitro Evidence

Contact Info

Product

Resources

About