Resveratrol attenuates manganese-induced oxidative stress and neuroinflammation through SIRT1 signaling in mice

• Published in: Food and chemical toxicology Vol. 153; p. 112283
• Main Authors: Cong, Lin, Lei, Meng-Yu, Liu, Zhi-Qi, Liu, Zhuo-Fan, Ma, Zhuo, Liu, Kuan, Li, Jing, Deng, Yu, Liu, Wei, Xu, Bin
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2021
• Subjects: Animals; Carbazoles - pharmacology; Chlorides; Hippocampus - drug effects; Hippocampus - pathology; Inflammation - chemically induced; Inflammation - drug therapy; Inflammation - metabolism; Learning - drug effects; Locomotion - drug effects; Manganese; Manganese Compounds; Memory - drug effects; Mice; Mice, Inbred C57BL; Morris Water Maze Test - drug effects; Neuroinflammation; Neurons - drug effects; Neuroprotective Agents - therapeutic use; Open Field Test - drug effects; Oxidative stress; Oxidative Stress - drug effects; Resveratrol; Resveratrol - therapeutic use; Signal Transduction - drug effects; Sirtuin 1 - metabolism; Sirtuin-1; Up-Regulation - drug effects; Sirtuin-1; Oxidative stress; Neuroinflammation; Resveratrol; Manganese
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2021.112283

Exposure to excess levels of manganese (Mn) leads to neurotoxicity. Increasing evidence demonstrates that oxidative stress and neuroinflammation are important pathological causes of neurotoxicity. Resveratrol (Rsv), a sirtuin-1 (SIRT1) activator, plays an important role in neuroprotection. However, the molecular mechanisms of Rsv alleviating Mn-induced oxidative stress and neuroinflammation are not fully understood. To evaluate whether Rsv treatment relieves the oxidative stress and neuroinflammation in the hippocampus after Mn exposure through SIRT1 signaling, C57BL/6 adult mice were exposed to MnCl2 (200 μmol/kg), Rsv (30 mg/kg), and EX527 (5 mg/kg). Our results showed that administering MnCl2 for 6 weeks caused behavioral impairment and nerve cell injury in hippocampal tissue, which was related to oxidative stress and neuroinflammation. Activating Mn-induced JNK and inhibiting SIRT1 increased the phosphorylated and acetylated levels of NF-κB and STAT3, respectively. However, Rsv reduced the phosphorylated and acetylated levels of NF-κB and STAT3, and attenuated Mn-induced oxidative stress and inflammatory cytokines by activating SIRT1 signaling. Most importantly, EX527, a potent SIRT1 inhibitor, inactivated SIRT1, which prevented Rsv from exerting its beneficial effects. Taken together, our findings revealed that Rsv alleviated Mn-induced oxidative stress and neuroinflammation in adult mice by activating SIRT1. [Display omitted] •Rsv alleviated behavioral impairments and nerve cell injury in Mn-treated mice.•Rsv alleviated Mn-induced oxidative stress by up-regulating SIRT1.•Rsv reduced the acetylation levels of NF-κB and STAT3 by activating SIRT1 signaling.•Rsv alleviated Mn-induced neuroinflammation in adult mice by activating SIRT1.