Grape seed procyanidin extract protects against Pb-induced lung toxicity by activating the AMPK/Nrf2/p62 signaling axis. (June 2018)

• Record Type: Journal Article
• Authors: Lu, Jingjing; Jiang, Huijie; Liu, Biying; Baiyun, Ruiqi; Li, Siyu; Lv, Yueying; Li, Da; Qiao, Senqiu; Tan, Xiao; Zhang, Zhigang
• Is Part Of: Food and chemical toxicology. Volume 116:Part B(2018)
• Page Start: 59
• Page End: 69
• Publication Date: 2018-06
• Subjects: Grape seed procyanidin extract -- Pb -- Lung injury -- Oxidative stress -- AMPK/Nrf2/p62; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2018.03.034
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Lead (Pb) is one of the most relevant heavy metals contaminants which cause oxidative stress and threaten human health. The lung is one of the organs most severely damaged by Pb. In this study, we investigated the protective effect of grape seed procyanidin extract (GSPE) on Pb-induced lung injury in rats. We found that GSPE alleviated Pb-induced lung injury by relieving oxidative stress, reducing release of inflammatory factors, and inhibiting apoptosis. Furthermore, GSPE enhanced the antioxidant defense systems by activating the nuclear factor-erythroid-2-related factor (Nrf2) signaling pathway to promote downstream expression of heme oxygenase 1 and NAD(P)H quinone oxidoreductase 1. The subsequent ubiquitin-binding protein p62 (sequestosome 1), a downstream target of Nrf2, formed a positive feedback loop with Nrf2 during oxidative stress responses. GSPE treatment resulted in activation of adenosine monophosphate-activated protein kinase (AMPK), which was highly involved in Nrf2 activation. Overall, our findings demonstrate that theprotective effect of GSPE on Pb-induced lung injury arises from activation of the AMPK/Nrf2/p62 signaling pathway, thus providing a new approach for treatment of Pb intoxication. Graphical abstract: Image 1 Highlights: Grape seed procyanidin extract inhibits lead-induced oxidative stress by activating AMPK/Nrf2/p62. Grape seed procyanidin extract treatment attenuates inflammation and apoptosis induced by lead. Grape seed procyanidin extract reduces the accumulation of lead in rat lungs.