Resveratrol attenuates manganese-induced oxidative stress and neuroinflammation through SIRT1 signaling in mice
| Autor: | Meng-Yu Lei, Jing Li, Bin Xu, Wei Liu, Zhuo-Fan Liu, Lin Cong, Yu Deng, Kuan Liu, Zhi-Qi Liu, Zhuo Ma |
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| Rok vydání: | 2021 |
| Předmět: |
Carbazoles
Pharmacology Resveratrol Toxicology medicine.disease_cause Neuroprotection Hippocampus Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound 0404 agricultural biotechnology Chlorides Sirtuin 1 Memory Morris Water Maze Test medicine Animals Learning STAT3 Neuroinflammation 030304 developmental biology Inflammation Neurons 0303 health sciences biology Chemistry Neurotoxicity 04 agricultural and veterinary sciences General Medicine medicine.disease 040401 food science Up-Regulation Mice Inbred C57BL Oxidative Stress Neuroprotective Agents Manganese Compounds biology.protein Open Field Test Oxidative stress Locomotion Food Science Signal Transduction |
| Zdroj: | Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 153 |
| ISSN: | 1873-6351 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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