title: Dose dependent cytotoxicity of pranoprofen in cultured human corneal endothelial cells by inducing apoptosis.
abstract: Pranoprofen (PPF), a non-steroidal anti-inflammatory drugs (NSAIDs), is often used in keratitis treatment in clinic. Several studies have assessed in vitro the cytotoxicity of topical NSAIDs to corneal epithelial cells due to its importance for predicting human corneal toxicity. Damage by cytotoxic drugs can result in excessive loss of human corneal endothelial (HCE) cells which lead to decompensation of the endothelium and eventual loss of visual acuity. However, the endothelial cytotoxicity of PPF has not yet been reported using an in vitro model of HCE cells. This study assessed the cytotoxicity of PPF to HCE cells and its underlying mechanism. Cellular viability was determined using inverted phase contrast light microscopy, and plasma membrane permeability, genomic DNA fragmentation, and ultrastructure were detected by acridine orange/ethidium bromide staining, DNA agarose gel electrophoresis, and transmission electron microscopy (TEM), respectively. The results on cellular viability showed that PPF at concentrations ranging from 0.0625 to 1.0 g/l had poignant cytotoxicity to HCE cells, and the extent of its cytotoxicity was dose- and time-dependent. Further characterization indicated that PPF induced plasma membrane permeability elevation, DNA fragmentation, and apoptotic body formation, proving its apoptosis inducing effect on HCE cells. In conclusion, PPF above 0.0625 g/l has poignant cytotoxicity on HCE cells in vitro by inducing cell apoptosis, and should be carefully employed in eye clinic.
authors.affiliation: Laboratory for Corneal Tissue Engineering, College of Marine Life Sciences, Ocean University of China , Qingdao , China and.
authors.forename: Yi-Han
authors.initials: YH
authors.lastname: Li
authors.forename: Qian
authors.initials: Q
authors.lastname: Wen
authors.forename: Ting-Jun
authors.initials: TJ
authors.lastname: Fan
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ge
authors.forename: Miao-Miao
authors.initials: MM
authors.lastname: Yu
authors.forename: Ling-Xiao
authors.initials: LX
authors.lastname: Sun
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D001578:Benzopyrans / Q000008:administration & dosage / Q000633:toxicity; D018929:Cell Culture Techniques; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000648:ultrastructure; D004728:Endothelium, Corneal / Q000187:drug effects* / Q000648:ultrastructure; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008858:Microscopy, Phase-Contrast; D011422:Propionates / Q000008:administration & dosage / Q000633:toxicity; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001578:Benzopyrans; D011422:Propionates; C043940:pyranoprofen
keywords: Apoptosis; cytotoxicity; human corneal endothelial cell; pranoprofen