To explore the mechanism of neurotoxicity of carbon monoxide based on network toxicology

Liu Jing; Lei Li; Yang Tian; Zhao Yibo; Zou Jingyu; Liu Bin; Luo Yuwei

doi:10.3969/j.issn.1002-1949.2025.08.004

Abstract：Objective To explore the mechanism of carbon monoxide(CO)-induced neurodamage based on network toxicology.Methods This study analyzed the neurotoxic mechanism of CO by using network toxicology and molecular docking techniques.First,the three-dimensional structure of CO was obtained from PubChem,and its toxicity information was queried on the ProTox platform.The target gene set of CO was analyzed by using the Venn package,and brain injury-related genes were screened in combination with the GeneCards,OMIM,and TTD databases to construct the target gene set.Cytoscape was used to build an interaction network of CO targets and brain injury,identifying high-connectivity target proteins.Gene ontology(GO)and Kyoto encyclopedia of gene and genomes(KEGG)enrichment analyses were performed on key targets to identify the pathways related to CO poisoning and brain injury,with the results presented in a bubble chart.Finally,molecular docking analysis was conducted by using CB-dock2 to verify the binding ability of key target proteins to CO.Results This study constructed the CO-brain injury target network,revealing the mechanisms of CO damage to the nervous system,particularly the disruption of the blood-brain barrier.GO and KEGG enrichment analyses indicated that CO mediated neurodamage through the heme metabolism process and porphyrin synthesis pathway,with HMOX1 potentially playing a key role in this process.Conclusions HMOX1 possibly plays a critical role in further exploration of the neurotoxic mechanisms of CO.