Coenzyme Q10 ameliorates lipopolysaccharide-induced acute lung injury by attenuating oxidative stress and NLRP3 inflammation through regulating mitochondrial dynamics.

Increasing evidence has demonstrated that coenzyme Q10 (CoQ10) exhibits a range of biological properties. Herein, we explored the protective effect and potential molecular mechanism of CoQ10 on lipopolysaccharide (LPS)-induced acute lung injury (ALI). We found that medium (10 mg/kg) and high (50 mg/kg) doses of CoQ10 ameliorated LPS (50 µg/µL)-induced ALI to varying degrees, as demonstrated by reduced lung coefficient, lower wet/dry weight lung tissue ratio, decreased bronchoalveolar lavage fluid protein concentration, less anatomical and histopathological damage to the lung, and increased expression of proteins related to lung epithelial barrier structure. CoQ10 also alleviated LPS-induced oxidative stress and inflammation mediated by NOD-like receptor protein 3 (NLRP3) by reducing the reactive oxygen species (ROS), malondialdehyde, and mitochondrial ROS concentrations, increasing superoxide dismutase, glutathione, and catalase activity, and decreasing NLRP3 expression at the protein and mRNA levels. Moreover, CoQ10 alleviated structural and functional damage to the mitochondria, inhibited mitochondrial fission, and promoted mitochondrial fusion, mainly by inhibiting phosphorylation of dynamin-related protein 1 (Drp1) at Ser616 and Ser637. Correlation analysis revealed that mitochondrial fission (especially Drp1) was positively correlated with oxidative stress, NLRP3-mediated inflammation, and structural damage to the lung epithelial barrier. Molecular docking analysis showed that CoQ10 binds stably to Drp1, with a binding energy of -5.9 kcal/mol. Furthermore, the use of schaftoside (a Drp1 inhibitor) has further elucidated the mechanism of action of CoQ10. Together, these results suggest that CoQ10 alleviates LPS-induced ALI by regulating mitochondrial dynamics, attenuating oxidative stress, and decreasing NLRP3-medated inflammation, thereby promoting lung epithelial barrier structural remodeling.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)