Abstract:AIM:To explore the toxicological mechanisms of benzalkonium chloride(BAC)as a preservative in ophthalmic preparations leading to corneal injury in dry eye.
METHODS:Network toxicology was employed to obtain the chemical structure of BAC, its toxic targets, and targets associated with dry eye-related corneal injury from databases including PubChem, CTD, ChEMBL, and STITCH. The protein-protein interaction(PPI)networks were constructed using the STRING database to screen key toxicity targets. Gene ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to elucidate the potential biological processes and signaling pathways affected by BAC. Furthermore, molecular docking techniques were employed to validate the binding affinity of BAC to its key targets(IL-6, IL-1β, TNF, and EGF).
RESULTS:BAC had a toxicity grade of 4 and exhibited significant eye irritation. A total of 85 common targets of BAC and dry eye corneal damage were screened out, of which 49 were key toxic targets, including TNF, IL-6, TP53, IL-1β, BCL2, etc. KEGG enrichment analysis showed that BAC mainly acted on 7 corneal injury pathways closely associated with corneal injury, such as IL-17, TNF, NF-κB, JAK-STAT, PI3K-Akt, Rap1, and MAPK. The results of molecular docking showed that BAC had stable binding ability to IL-6, IL-1β, TNF, EGF, and other targets(binding energy <0).
CONCLUSION:BAC may induce corneal damage in dry eye through multi-target and multi-pathway mechanisms, involving processes such as inflammatory response, apoptosis, disruption of tear film stability, and delayed corneal repair, which suggests that long-term use of ophthalmic preparations containing BAC may aggravate ocular surface damage.
