Department of Forensic Medicine & Toxicology, Faculty of Veterinary Medicine, Zagazig University, Egypt.
Anatomy Department, Faculty of Veterinary Medicine, Kafrelsheikh University, Egypt.
Biomed Pharmacother. 2022 Jul;151:113160. doi: 10.1016/j.biopha.2022.113160. Epub 2022 May 20.
Recently, we reported that quercetin (Que) could alleviate immunotoxicity induced by pristine multi-walled carbon nanotubes (MWCNTs) in mice. In the present study, we explored whether Que could also relieve MWCNTs-induced neurotoxicity. MWCNTs injection induced a dose-dependent neurotoxic effect in mice as evidenced by increased oxidative stress, inflammation, and pyroptosis in the brain. However, treatment with Que ameliorated MWCNTs-induced neurotoxicity as revealed by 1) elevated acetylcholinesterase (AChE) activity, 2) reduced lipid peroxidation biomarker malondialdehyde (MDA), 3) improved antioxidant status as indicated by increased levels of reduced glutathione (GSH) and activities of superoxide dismutase (SOD), catalase (CAT), as well as upregulated expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) genes, 4) decreased levels and expression of inflammatory biomarkers [nitric oxide (NO), interleukin 1 beta (IL1ß), tumor necrosis factor-alpha (TNFα), and nuclear factor kappa B (NF-κB)], 5) downregulated expression of pyroptosis-related genes [nod-like receptor protein inflammasome 3 (Nlrp3) and caspase 1 (Casp1)] but with no effect on the apoptotic Casp3 gene, 6) minimized axonal degeneration and number of microglia in the cerebral medulla, and 7) diminished the number of degenerated neurons in hippocampus and cerebellum. Taken together, Que could ameliorate MWCNT-induced neurotoxicity through antioxidant, anti-inflammatory, and anti-pyroptotic mechanisms.
最近，我们报道了槲皮素（Que）可以减轻原始多壁碳纳米管（MWCNTs）在小鼠中引起的免疫毒性。在本研究中，我们探讨了 Que 是否也可以减轻 MWCNTs 引起的神经毒性。MWCNTs 注射在小鼠中引起了剂量依赖性的神经毒性作用，这表现在大脑中的氧化应激、炎症和细胞焦亡增加。然而，Que 的治疗改善了 MWCNTs 引起的神经毒性，具体表现在 1）乙酰胆碱酯酶（AChE）活性升高，2）脂质过氧化生物标志物丙二醛（MDA）降低，3）抗氧化状态改善，表现为还原型谷胱甘肽（GSH）水平升高和超氧化物歧化酶（SOD）、过氧化氢酶（CAT）的活性增加，以及核因子红细胞 2 相关因子 2（Nrf2）和血红素加氧酶-1（HO-1）基因的上调表达，4）炎症生物标志物[一氧化氮（NO）、白细胞介素 1β（IL1β）、肿瘤坏死因子-α（TNFα）和核因子κB（NF-κB）]水平和表达降低，5）细胞焦亡相关基因[核苷酸结合寡聚结构域样受体蛋白 3（Nlrp3）和半胱氨酸天冬氨酸蛋白酶 1（Casp1）]表达下调，但对凋亡 Casp3 基因没有影响，6）大脑髓质中的轴突变性和小胶质细胞数量减少，以及 7）海马和小脑中变性神经元数量减少。总之，Que 可以通过抗氧化、抗炎和抗细胞焦亡机制改善 MWCNT 诱导的神经毒性。
