Celastrol alleviates oxidative stress induced by multi-walled carbon nanotubes through the Keap1/Nrf2/HO-1 signaling pathway

Multi-walled carbon nanotubes (MWCNTs) mainly induce oxidative stress through the overproduction of reactive oxygen species (ROS), which can lead to cytotoxicity. Celastrol, a plant-derived compound, can exert antioxidant effects by reducing ROS production. Our results indicated that exposure to MWCNTs decreased cell viability and increased ROS production. Nrf2 knockdown (kd) led to increased ROS production and enhanced MWCNT-induced cytotoxicity. Keap1-kd led to decreased ROS production and attenuated cytotoxicity. Treatment with celastrol significantly decreased ROS production and promoted Keap1 protein degradation through the lysosomal pathway, thereby enhancing the translocation of Nrf2 from the cytoplasm to the nucleus and increasing HO-1 expression. The in vivo results showed that celastrol could alleviate the inflammatory damage of lung tissues, increase the levels of the antioxidants, GSH and SOD, as well as promote the expression of the antioxidant protein, HO-1 in MWCNT-treated mice. Celastrol can alleviate MWCNT-induced oxidative stress through the Keap1/Nrf2/HO-1 signaling pathway.

Automated summary

The study found that multi-walled carbon nanotubes (MWCNTs) induce oxidative stress by overproducing reactive oxygen species (ROS), leading to cytotoxicity. However, celastrol, a plant-derived compound, has antioxidant effects by reducing ROS production. The results showed that MWCNT exposure decreased cell viability and increased ROS production. Knockdown of Nrf2 increased ROS production and cytotoxicity, while knockdown of Keap1 decreased ROS production and attenuated cytotoxicity. Treatment with celastrol significantly reduced ROS production and promoted Keap1 degradation, leading to increased Nrf2 translocation to the nucleus and increased HO-1 expression. In vivo results demonstrated that celastrol alleviated inflammatory damage in lung tissues, increased levels of antioxidants, GSH and SOD, and promoted HO-1 expression in MWCNT-treated mice. Therefore, celastrol can alleviate MWCNT-induced oxidative stress through the Keap1/Nrf2/HO-1 signaling pathway.