Quercetin Attenuates Manganese-Induced Neuroinflammation by Alleviating Oxidative Stress through Regulation of Apoptosis, iNOS/NF-κB and HO-1/Nrf2 Pathways

Bahar, Entaz; Kim, Ji-Ye; Yoon, Hyonok

doi:10.3390/ijms18091989

Cited by 126 publications

(72 citation statements)

References 54 publications

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“…Previous studies have shown that Mn caused generation of reactive oxygen species (ROS). 23 Rap did not alter generation of ROS, suggesting that mTORC is a target downstream of ROS. Indeed, ROS caused activation of mTORC, which contributed to induction of the IRE1 pathway, but not the PERK and ATF6 pathways.…”

Section: Discussionmentioning

confidence: 87%

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Effect of the cross‐talk between autophagy and endoplasmic reticulum stress on Mn‐induced alpha‐synuclein oligomerization

Liu

Yan

Tan

et al. 2017

Environmental Toxicology

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Overexposure to manganese (Mn) has been known to induce alpha-synuclein (α-Syn) oligomerization, which is degraded mainly depending on endoplasmic reticulum stress (ER stress) and autophagy pathways. However, little data reported the cross-talk between ER stress and autophagy on Mn-induced α-Syn oligomerization. To explore the relationship between ER stress and autophagy, we used 4-phenylbutyric acid (4-PBA, the ER stress inhibitor), rapamycin (Rap, autophagy activator) and 3-methyladenine (3-MA, autophagy inhibitor) in mice model of manganism. After 4 weeks of treatment with Mn, both ER stress and autophagy were activated. Exposed to Mn also resulted in α-Syn oligomerization and neuronal cell damage in the brain tissue of mice, which could be relieved by 4-PBA pretreatment. Moreover, when the ER stress was inhibited, the activation of autophagy was also inhibited. Rap pretreatment significantly activated autophagy and decreased α-Syn oligomers. However, 3-MA pretreatment inhibited autophagy resulting in increase of α-Syn oligomers, and compensatorily activated PERK signaling pathway. Our results also demonstrated that the inhibition of autophagy by 3-MA aggravated neuronal cell damage. The findings clearly demonstrated that the cross-talking between autophagy and ER stress might play an important role in the α-Syn oligomerization and neurotoxicity by Mn.

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Section: Discussionmentioning

confidence: 87%

“…The results showed that Rap pretreatment significantly activated autophagy and IRE1 signaling pathway, as well as partially decreased α‐Syn oligomers. Previous studies have shown that Mn caused generation of reactive oxygen species (ROS) . Rap did not alter generation of ROS, suggesting that mTORC is a target downstream of ROS.…”

Section: Discussionmentioning

confidence: 96%

Effect of the cross‐talk between autophagy and endoplasmic reticulum stress on Mn‐induced alpha‐synuclein oligomerization

Liu

Yan

Tan

et al. 2017

Environmental Toxicology

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“…As found in macrophages, quercetin activated the Kelch-like ECH-associated protein-1(Keap1)-Nrf2 signaling pathway to induce HO-1 expression for protection against oxidative stress and inflammatory responses [10]. Quercetin could effectively inhibit manganese-induced oxidative stress and inflammatory response in neuraltumor epithelialcells (SK-N-MC) in Sprague-Dawley rats though activating HO-1/Nrf2 and inhibiting the NF-κB pathway [31]. Additionally, quercetin could improve mitochondrial function by promoting the translocation of Nrf2 from the cytoplasm to the nucleus and activating the Nrf2 signaling pathway [32,33].…”

Section: Discussionmentioning

confidence: 96%

Quercetin Protects against Lipopolysaccharide-Induced Intestinal Oxidative Stress in Broiler Chickens through Activation of Nrf2 Pathway

Sun

Dong

et al. 2020

Molecules

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We investigated the potential ability of quercetin to protect against lipopolysaccharide (LPS)-induced intestinal oxidative stress in broiler chickens and the potential role of the Nrf2 (nuclear factor erythroid 2-related factor 2) signaling pathway. One-day-old broiler chickens (n = 240) were randomized into four groups: saline-challenged broiler chickens fed a basal diet (Con), LPS-challenged broiler chickens on a basal diet (LPS), and LPS-treated broiler chickens on a basal diet containing either 200 or 500 mg/kg of quercetin (Que200+LPS or Que500+LPS). Quercetin (200 mg/kg) significantly alleviated LPS-induced decreased duodenal, jejunal, and illeal villus height and increased the crypt depth in these regions. Quercetin significantly inhibited LPS-induced jejunal oxidative stress, including downregulated reactive oxygen species (ROS), malondialdehyde (MDA), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels, and it upregulated superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. Quercetin relieved LPS-induced jejunal mitochondria damage and upregulated mitochondrial DNA copy number-related gene expression, including cytochrome c oxidase subunit 1 (COX1), ATP synthase F0 subunit 6 (ATP6), and NADH dehydrogenase subunit 1 (ND1). Quercetin attenuated the LPS-induced inhibition of Nrf2 activation, translocation, and downstream gene expression, including heme oxygenase-1 (HO-1), NAD (P) H dehydrogenase quinone 1 (NQO1), and manganese superoxide dismutase (SOD2). Additionally, quercetin attenuated the LPS-inhibition of c-Jun N-terminal kinase (JNK), Extracellular Regulated protein Kinases (ERK), and p38MAPK (p38) phosphorylation in the MAPK pathway. Thus, quercetin attenuated LPS-induced oxidative stress in the intestines of broiler chickens via the MAPK/Nrf2 signaling pathway.

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“…3–3′ diaminobenzidine (DAB) was used as a chromogen. Staining of the background was performed using hematoxylin …”

Section: Methodsmentioning

confidence: 99%

Cardioprotective role of metformin against sodium arsenite‐induced oxidative stress, inflammation, and apoptosis

et al. 2019

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Arsenic is a universal component and a notable natural poison. Its exposure to people occurs primarily through natural, therapeutic, and occupational sources. This investigation intended to discover the defensive impact of metformin (100 and 150 mg/kg body weight) against sodium arsenite (SA)‐induced cardiotoxicity in experimental animals. The study was conducted on Sprague Dawley rats (n = 50), which were separated into five different groups as follows: control, met‐150, SA, SA + met‐100, and SA + met‐150. The results demonstrated that SA caused a significant increase in the level of malondialdehyde and also reduced activities of antioxidative enzyme. SA similarly increased inflammatory reactions by increasing the level of interleukin‐6, tumor necrosis factor‐α, and interleukin‐1β. In addition, SA provoked the apoptosis by expanding the p53 and Bax levels, terminal deoxynucleotidyl transferase dUTP nick end labeling, and expression of caspase‐3. SA altered the histological integrity of cardiac tissue and 8‐hydroxy‐2′‐deoxyguanosine expression. In conclusion, metformin significantly reduced oxidative stress, inflammatory reaction, and apoptotic pathway. The present investigation showed that metformin has a cardioprotective impact because of its protective role against oxidation, inflammation, and apoptosis.

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Quercetin Attenuates Manganese-Induced Neuroinflammation by Alleviating Oxidative Stress through Regulation of Apoptosis, iNOS/NF-κB and HO-1/Nrf2 Pathways

Cited by 126 publications

References 54 publications

Effect of the cross‐talk between autophagy and endoplasmic reticulum stress on Mn‐induced alpha‐synuclein oligomerization

Effect of the cross‐talk between autophagy and endoplasmic reticulum stress on Mn‐induced alpha‐synuclein oligomerization

Quercetin Protects against Lipopolysaccharide-Induced Intestinal Oxidative Stress in Broiler Chickens through Activation of Nrf2 Pathway

Cardioprotective role of metformin against sodium arsenite‐induced oxidative stress, inflammation, and apoptosis

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