Resveratrol alleviates alveolar epithelial cell injury induced by hyperoxia by reducing apoptosis and mitochondrial dysfunction

Abstract

Bronchopulmonary dysplasia is a severe and long-term pulmonary disease in premature infants. Hyperoxia-induced acute lung injury plays a critical role in bronchopulmonary dysplasia. Resveratrol is a polyphenolic phytoalexin and a natural agonist of Sirtuin 1. Many studies have shown that resveratrol has a protective effect on hyperoxia-induced lung damage, but its specific protective mechanism is still not clear. Further exploration of the possible protective mechanism of resveratrol was the main goal of this study. In this study, human alveolar epithelial cells were used to establish a hyperoxia-induced acute lung injury cell model, and resveratrol (Res or R), the Sirtuin 1 activator SRT1720 (S) and the Sirtuin 1 inhibitor EX-527 (E) were administered to alveolar epithelial cells, which were then exposed to hyperoxia to investigate the role of Res in mitochondrial function and apoptosis. We divided human alveolar epithelial cells into the following groups: (1) the control group, (2) hyperoxia group, (3) hyperoxia+Res20 group, (4) hyperoxia+Res20+E5 group, (5) hyperoxia+Res20+E10 group, (6) hyperoxia+S2 group, (7) hyperoxia+S2+E5 group, and (8) hyperoxia+S2+E10 group. Hyperoxia-induced cell apoptosis and mitochondrial dysfunction were alleviated by Res and SRT1720. Res and SRT1720 upregulated Sirtuin 1, PGC-1α, NRF1, and TFAM but decreased the expression of acetyl-p53 in human alveolar epithelial cells that were exposed to hyperoxia. These findings revealed that Res may alleviated hyperoxia-induced mitochondrial dysfunction and apoptosis in alveolar epithelial cells through the SIRT1/PGC-1a signaling pathway. Thus, Sirtuin 1 upregulation plays an important role in lung protection.

Effects of Hyperoxia on Mitochondrial Homeostasis: Are Mitochondria the Hub for Bronchopulmonary Dysplasia?

“…Studies have shown that the clinical drugs used to improve breathing, such as aminophylline and montelukast, can promote the biogenesis of human alveolar epithelium mitochondria through cAMP responsive element binding protein (CREB)/PGC-1α (Wang et al, 2019;Wei et al, 2019). The use of the mitochondrial antioxidant resveratrol can protect mtDNA and reduce apoptosis through SIRT1-PGC-1a (Wang et al, 2020;Zhu et al, 2021). These findings suggest that the biogenesis of mitochondria plays an important role in protecting against hyperoxic lung injuries.…”

Resveratrol Attenuates Hyperoxia Lung Injury in Neonatal Rats by Activating SIRT1/PGC-1α Signaling Pathway

“…Notably, our previous study showed that Res reduced hyperoxia-induced apoptosis and mitochondrial dysfunction in alveolar epithelial cells through the activation of SIRT1/PGC-1α. 22 Hence, the aim of this study was to establish a neonatal rat model of BPD to verify whether Res attenuates hyperoxia-induced lung injury through the SIRT1/PGC-1α signaling pathway.…”

Protective Effects and Potential Mechanisms of Dietary Resveratrol Supplementation on the Spleen of Broilers Under Heat Stress

“…The beneficial effects of RSV on cisplatin-induced oxidative stress, inflammation, and apoptosis in female rats' ovarian and uterine tissues have been discovered ( 55 ). RSV may alleviate hyperoxia-induced mitochondrial dysfunction and apoptosis in alveolar epithelial cells through the SIRT1/PGC-1α signaling pathway ( 56 ). Interestingly, in the present study, NT + RSV markedly decreased the relative gene expression of BAX compared with the NT group.…”