Abstract：
BACKGROUND: Cadmium (Cd) is a heavy metal with extremely harmful toxic effects on the brain. Quetiapine (QTP) has unique neuroprotective effects with anti-inflammatory and antioxidant actions. However, its neuroprotective effect against Cd-induced neurotoxicity has not been previously studied.
METHODS: QTP was administered in 10 and 20 mg/kg doses, while Cd was given in a dose of 6.5 mg/kg.
RESULTS: In our study, QTP dose-dependently attenuated neuronal injury by downregulating p-tau and β-amyloid. QTP potently attenuates histological abrasions induced by Cd. QTP counteracted oxidative injury by decreasing neuronal MDA and increased GSH levels mediated by downregulating Keap1 and upregulating Nrf2 and HO-1. QTP mitigated inflammation by decreasing MPO and NO2 and neuronal cytokines TNF-α and IL-1β and upregulating IL-10 levels mediated by NF-κB downregulation. Additionally, QTP counteracted Cd-induced pyroptosis by downregulating caspase-1, ASC, and NLRP3 protein levels.
CONCLUSIONS: In conclusion, QTP mitigates neurotoxicity induced by Cd through suppression of inflammation, pyroptosis, and oxidative stress by controlling the NF-κB, Keap1/Nrf2, and pyroptosis signals.
METHODS: QTP was administered in 10 and 20 mg/kg doses, while Cd was given in a dose of 6.5 mg/kg.
RESULTS: In our study, QTP dose-dependently attenuated neuronal injury by downregulating p-tau and β-amyloid. QTP potently attenuates histological abrasions induced by Cd. QTP counteracted oxidative injury by decreasing neuronal MDA and increased GSH levels mediated by downregulating Keap1 and upregulating Nrf2 and HO-1. QTP mitigated inflammation by decreasing MPO and NO2 and neuronal cytokines TNF-α and IL-1β and upregulating IL-10 levels mediated by NF-κB downregulation. Additionally, QTP counteracted Cd-induced pyroptosis by downregulating caspase-1, ASC, and NLRP3 protein levels.
CONCLUSIONS: In conclusion, QTP mitigates neurotoxicity induced by Cd through suppression of inflammation, pyroptosis, and oxidative stress by controlling the NF-κB, Keap1/Nrf2, and pyroptosis signals.
摘要：
背景：镉（Cd）是一种重金属，对大脑具有极其有害的毒性作用。喹硫平（QTP）具有独特的神经保护作用，具有抗炎和抗氧化作用。然而,以前尚未研究其对Cd诱导的神经毒性的神经保护作用。
方法：QTP以10和20mg/kg的剂量给药，而Cd的剂量为6.5mg/kg。
结果：在我们的研究中，QTP通过下调p-tau和β-淀粉样蛋白剂量依赖性地减弱神经元损伤。QTP可有效减轻Cd引起的组织学擦伤。QTP通过下调Keap1和上调Nrf2和HO-1介导的降低神经元MDA和增加GSH水平来抵消氧化损伤。QTP通过降低MPO和NO2以及神经元细胞因子TNF-α和IL-1β以及上调NF-κB下调介导的IL-10水平来减轻炎症。此外,QTP通过下调caspase-1，ASC，和NLRP3蛋白水平。
结论：结论：QTP通过抑制炎症减轻Cd引起的神经毒性，焦亡,通过控制NF-κB和氧化应激，Keap1/Nrf2和焦亡信号。
方法：QTP以10和20mg/kg的剂量给药，而Cd的剂量为6.5mg/kg。
结果：在我们的研究中，QTP通过下调p-tau和β-淀粉样蛋白剂量依赖性地减弱神经元损伤。QTP可有效减轻Cd引起的组织学擦伤。QTP通过下调Keap1和上调Nrf2和HO-1介导的降低神经元MDA和增加GSH水平来抵消氧化损伤。QTP通过降低MPO和NO2以及神经元细胞因子TNF-α和IL-1β以及上调NF-κB下调介导的IL-10水平来减轻炎症。此外,QTP通过下调caspase-1，ASC，和NLRP3蛋白水平。
结论：结论：QTP通过抑制炎症减轻Cd引起的神经毒性，焦亡,通过控制NF-κB和氧化应激，Keap1/Nrf2和焦亡信号。
