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

Abstract

Abstract. Sirtuin 1 (SIRT1) acts via the deacetylation of a number of crucial transcription factors and has been implicated in various biological processes, including oxidative stress. Previous studies have indicated that nuclear factor, erythroid 2-like 2 (NRF2) is an effective target of antioxidant therapy for paraquat (PQ) poisoning. However, the association between SIRT1 and NRF2 and their effects in PQ-induced oxidative stress remains to be elucidated. The current study demonstrated that PQ exposure upregulated the expression of SIRT1 and NRF2 following 6-and 24-h exposure in the lungs of mice. However, long-term exposure to PQ significantly decreased the expression of SIRT1 and NRF2. Resveratrol is a SIRT1 activator, and strongly enhanced SIRT1 expression and attenuated the lung injury resulting from PQ exposure in the current study. Additionally, treatment with resveratrol upregulated the expression of NRF2 and glutathione, increased the activity of heme oxygenase-1, superoxide dismutase and catalase, but depleted the expression of malondialdehyde. The present results demonstrated that resveratrol reduced PQ-induced oxidative stress and lung injury, potentially through the positive feedback signaling loop between SIRT1 and NRF2.

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

“…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.…”

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

“…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.…”

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

“…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, ).…”

“…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.…”