Quercetin attenuates SiO2-induced ZBP-1-mediated PANoptosis in mouse neuronal cells via the ROS/TLR4/NF-κb pathway

With the increasing development of the society, silicon dioxide (SiO2) has been used in various fields, such as agriculture, food industry, etc., and its residues can pose a potential health threat to organisms. Quercetin (Que) is a potent free radical scavenger commonly found in plants. C57BL/6 mice were chosen to established a mouse model of SiO2 exposure and Que antagonism to investigate the mechanism of action of Que in rescuing the toxic damage of SiO2 on mouse cerebellum tissue. The results showed that cytoplasmic vacuolization, and inflammatory cell infiltration caused by SiO2 were alleviated by the addition of Que, and reduced oxidative stress in mouse cerebellum, alleviated the activation of TLR4 pathway induced by SiO2, and substantially reduced the occurrence of ZBP-1-mediated PANoptosis induced by SiO2 exposure in mouse cerebellum. In NS20Y cells, the oxidative stress activator (Elesclomol) and inhibitor N-acetyl cysteine (NAC), and the NF-kappa B activator 2 (NA2) were added. Elesclomol and NAC confirm the involvement of ROS in regulating the TLR4/NF-kappa B pathway, the TLR4/NF-kappa B pathway regulated ZBP-1-mediated PANoptosis in cerebellum and NS20Y cells induced by SiO2 exposure. In conclusion, the present experimental data suggest that Que mitigates the onset of ZBP-1-mediated PANoptosis in neuronal cells induced by SiO2 through the ROS/TLR4/NF-kappa B pathway. The present experimental findings help to understand the detoxification effect of Que in more tissues and provide an important reference for the rescue of organisms in long-term SiO2 environment.