Cytotoxic effect of proparacaine on human corneal epithelial cells and its possible mechanisms

다국어 초록 (Multilingual Abstract)

Excessive use of proparacaine (PPC), a commonly used anesthetic for eye surgery, may damage the human corneal epithelium (HCEP) and impair vision. The cytotoxicity of PPC on the HCEP and its possible mechanism of action remain unclear. Therefore, we treated HCEP cells with 0.15625-5 g/L PPC for 1-28 h and monitored its effects. We found that PPC at concentrations above 0.15625 g/L (1/32 of the clinical therapeutic dose) induced dose- and time-dependent cytotoxic morphological changes and reduced cell viability. Moreover, PPC induced G1 phase arrest, plasma membrane permeability, phosphatidylserine externalization, DNA fragmentation, and apoptotic body formation. Furthermore, PPC induced activation of caspase-3, -8, and -9, disrupted mitochondrial transmembrane potential, upregulated BAD and down-regulated Bcl-2 expression, and induced the release of cytochrome c and apoptosis-inducing factor from the mitochondria. Our results indicate that PPC is cytotoxic to HCEP cells and induces apoptosis via a death receptor-mediated mitochondrion-dependent pathway.

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