Resveratrol protects mice from paraquat-induced lung injury: The important role of SIRT1 and NRF2 antioxidant pathways

Li, Shengqin; Zhao, Guangju; Chen, Longwang; Ding, Yinwei; Lian, Jie; Hong, Guangliang; Lu, Zhongqiu

doi:10.3892/mmr.2015.4710

Cited by 75 publications

(49 citation statements)

References 22 publications

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“…It was founded that MA inhibited the expression of SIRT1 by inducing oxidative stress with elevated ROS levels, increased SOD and reduced GCS. MA‐induced lung toxicity is linked to oxidative injury by directly activating NAPDH oxidase and generating of ROS that cause cellular damages . Previous studies reported that MA increased ROS production in lungs, which are consistent with the results of the current study.…”

Section: Discussionsupporting

confidence: 93%

Resveratrol protects the integrity of alveolar epithelial barrier via SIRT1/PTEN/p‐Akt pathway in methamphetamine‐induced chronic lung injury

et al. 2020

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Objectives SIRT1 is an antioxidative factor, but its mechanism in methamphetamine (MA)‐induced lung injury remains unclear. The purpose of this study is to determine whether MA can disrupt the integrity of alveolar epithelial barrier, whether SIRT1 is involved in MA‐induced chronic lung injury and whether Resveratrol (Res) can protect the integrity of alveolar epithelial cells by regulating ROS to activate SIRT1/PTEN/p‐Akt pathway. Materials and methods The rats were randomly divided into control group and MA group. Extracted lungs were detected by Western blot, HE staining and immunohistochemistry. The alveolar epithelial cells were treated with MA or/and Res, following by Western blot, LDH leakage assay and flow cytometry. MOE is used for bio‐informatics prediction. Results Chronic exposure to MA can cause slower growth ratio of weight, increased RVI and induced lung injury including the reduced number of alveolar sacs and the thickened alveolar walls. MA‐induced apoptosis was associated with SIRT1‐related oxidative stress. Res suppressed ROS levels, activated SIRT1, negatively regulated PTEN, phosphorylated Akt, reduced LDH leakage, increased the expression of ZO‐1 and E‐cadherin and inhibited the apoptosis of alveolar epithelial cells to attenuate MA‐induced higher permeability of alveolar epithelium. Conclusions MA disrupted the integrity of alveolar epithelial barrier. Res inhibited oxidative stress and reversed MA‐induced higher permeability and apoptosis of alveolar epithelium by the activation of SIRT1/PTEN/p‐Akt pathway.

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Section: Discussionsupporting

confidence: 93%

Resveratrol protects the integrity of alveolar epithelial barrier via SIRT1/PTEN/p‐Akt pathway in methamphetamine‐induced chronic lung injury

et al. 2020

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“…In the present study, SIRT1 overexpression was associated with a high level of GSH, as well as SOD and CAT activities, the downstream genes of NRF2-anti-ARE, whereas the depletion of SIRT1 markedly increased the activity of MDA and HO-1, which suggested that SIRT1 protein may play an important role in mediating the oxidant-antioxidant balance in PQ-induced pulmonary injury (39) and enhanced cell resistance to oxidative stress. In a previous study of ours (40), resveratrol, an activator of SIRT1, increased the SIRT1 and NRF2 levels, and through the activation of the NRF2-ARE pathway led to the suppression of ROS production.. In that study, we demonstrated that PQ stimulated the compensatory overexpression of SIRT1 and NRF2, whereas exposure to PQ for a longer period of time significantly decreased the expression of SIRT1, as well as NRF2 in the lungs of mice.…”

Section: Discussionmentioning

confidence: 47%

SIRT1 exerts protective effects against paraquat-induced injury in mouse type II alveolar epithelial cells by deacetylating NRF2 in vitro

Ding

Zhao

et al. 2016

International Journal of Molecular Medicine

122

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Silent information regulator 2-related enzyme 1 (SIRT1), a protein deacetylase, is known to strongly protect cells against oxidative stress-induced injury. The nuclear factor E2-related factor 2 (NRF2)-antioxidant response element (ARE) antioxidant pathway plays important regulatory roles in the antioxidant therapy of paraquat (PQ) poisoning. In the present study, we investigated whether the SIRT1/NRF2/ARE signaling pathway plays an important role in lung injury induced by PQ. For this purpose, mouse type II alveolar epithelial cells (AECs‑II) were exposed to various concentrations of PQ. The overexpression or silencing of SIRT1 was induced by transfecting the cells with a SIRT1 overexpression vector or shRNA targeting SIRT1, respectively. The protein expression levels of SIRT1 and NRF2 were measured by western blot analysis. The superoxide dismutase (SOD) and catalase (CAT) activities, as well as the glutathione (GSH) and malondialdehyde (MDA) levels were measured using respective kits. Heme oxygenase-1 (HO-1) activity was also determined by ELISA. In addition, cell apoptosis was determined by flow cytometry. The protein stability of NRF2 was analyzed using cycloheximide and its acetylation in the cells was also determined. The following findings were obtained: i) SIRT1 overexpression markedly increased NRF2 protein expression; ii) SIRT1 promoted the transcriptional activity of NRF2 and upregulated the expression of the NRF2 downstream genes, SOD, CAT, GSH and HO-1, thus inhibiting the apoptosis of AECs‑II; iii) the inhibition of SIRT1 activity further induced the production of malondialdehyde (MDA), which resulted in increased oxidative damage; iv) SIRT1 promoted the stability of NRF2 by regulating the deacetylation and activation of the NRF2/ARE antioxidant pathway. The findings of this study demonstrate that the protective effects of SIRT1 are associated with the activation of the NRF2/ARE antioxidant pathway in lung injury induced by PQ poisoning.

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“…Previous studies reported that Nrf2 can be activated or inhibited upon stress conditions. For example, Nrf2 mRNA and protein levels are increased at 6 and 24 hr after paraquat administration but are decreased at 72 hr (Li et al, ). In human umbilical vein endothelial cells, 50–100 μg/ml PM2.5 elevated the level of Nrf2, whereas a decreased expression of Nrf2 was observed at 200–400 μg/ml PM2.5 (Yang et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…The protective effects of resveratrol against oxidative stress can be mediated through an Nrf2‐dependent mechanism (Canella et al, ; Li et al, ). Our results illustrated that resveratrol alleviated PM2.5‐induced oxidative stress and inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Modulation of autophagy in the protective effect of resveratrol on PM2.5‐induced pulmonary oxidative injury in mice

et al. 2018

Phytotherapy Research

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Ambient fine particulate matter (PM2.5) is capable of inducing pulmonary oxidative injury. Autophagy maintains basal cellular homeostasis and plays a critical role in the pathogenesis of lung diseases. Resveratrol, a natural polyphenol, is an effective antioxidant agent against particulate matter (PM)-induced injuries. The current study was designed to investigate whether resveratrol can regulate autophagy in the process of PM2.5-mediated pulmonary oxidative injury. In the mice model of PM2.5 exposure, we found that PM2.5 increased the contents of malondialdehyde (MDA) and nitric oxide (NO) while decreased the expression of nuclear factor erythroid-2-related factor 2 in the lungs. The levels of 8-hydroxydeoxyguanosine and inflammatory cytokines were increased following PM2.5 exposure. Histological analysis of the lungs revealed inflammatory change in PM2.5 group. Meanwhile, PM2.5 triggered autophagy, as evidenced by the elevated expression of microtubule-associated proteins light chain 3II, Beclin1 and p62. Transmission electron microscopy images showed that autophagosomes accumulated in the lungs after PM2.5 exposure. Furthermore, resveratrol intervention suppressed autophagy and attenuated the oxidative injury resulting from PM2.5 exposure. Our findings provided a valuable insight into the underlying mechanism for the protective effects of resveratrol against PM2.5-induced lung injury, which involves suppression of the autophagic process. KEYWORDS autophagy, lung, oxidative injury, PM2.5, resveratrol * Yuan Li and Suming Fu contributed equally to this work.

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Resveratrol protects mice from paraquat-induced lung injury: The important role of SIRT1 and NRF2 antioxidant pathways

Cited by 75 publications

References 22 publications

Resveratrol protects the integrity of alveolar epithelial barrier via SIRT1/PTEN/p‐Akt pathway in methamphetamine‐induced chronic lung injury

Resveratrol protects the integrity of alveolar epithelial barrier via SIRT1/PTEN/p‐Akt pathway in methamphetamine‐induced chronic lung injury

SIRT1 exerts protective effects against paraquat-induced injury in mouse type II alveolar epithelial cells by deacetylating NRF2 in vitro

Modulation of autophagy in the protective effect of resveratrol on PM2.5‐induced pulmonary oxidative injury in mice

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