title: The effect of resveratrol on protecting corneal epithelial cells from cytotoxicity caused by moxifloxacin and benzalkonium chloride.
abstract: OBJECTIVE
  Moxifloxacin (MOX), a fourth generation fluoroquinolone (FQ), has a wide antibacterial spectrum, but may show cytotoxicity characterized by high productions of reactive oxygen species (ROS). This study investigated the protective role of a common antioxidant agent, resveratrol (trans-3,5,4'-trihydroxystilbene), against the cytotoxicity caused by MOX.
  
  
  METHODS
  Experiments were performed with a human corneal epithelial cell line (HCECs; ATCC-CRL-11515). Another commonly used FQ, levofloxacin (LEV), and the most commonly used preservatives, benzalkonium chloride (BAC), were also used for comparison with MOX. Cell viability and morphologic changes after treatment were evaluated with trypan blue exclusion assay, propidium iodine/annexin V-FITC staining, and flow cytometry. Chemiluminescence immunoassay was used for ROS quantification. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, wound healing assay, and intracellular detections of oxidative stress were performed to evaluate the effects of resveratrol.
  
  
  RESULTS
  The MOX group, similar to the BAC group, showed significant cell shrinkage and death compared with the LEV group. High ROS production in HCECs of MOX group was observed both by chemiluminescence immunoassay and intracellular images. Within the observations of MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay, live cell images, and wound healing process in vitro, the cytotoxic effects of the MOX and BAC groups were opposed by resveratrol. Human corneal epithelial cells pretreated with resveratrol demonstrated better cell viability and healing rate in the early stage.
  
  
  CONCLUSIONS
  The protective effects of antioxidant agents indicate that MOX, similar to BAC, causes oxidative stress-related cell damage. The results also inspired us to think about a "supplementary regimen" to increase safety and decrease the adverse effect in the treatment of corneal infections.
authors: Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan Department of Ophthalmology, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
authors: Tzu-Yun
authors: TY
authors: Tsai
authors: Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan.
authors: Ta-Ching
authors: TC
authors: Chen
authors: Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan Department of Ophthalmology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: I-Jong
authors: IJ
authors: Wang
authors: Department of Pathology, University of Southern California, Los Angeles, California, United States.
authors: Chao-Yuan
authors: CY
authors: Yeh
authors: Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: Ming-Jai
authors: MJ
authors: Su
authors: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: Ruey-Hua
authors: RH
authors: Chen
authors: Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan.
authors: Tzu-Hsun
authors: TH
authors: Tsai
authors: Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan Department of Ophthalmology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: Fung-Rong
authors: FR
authors: Hu
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001548:Benzalkonium Compounds / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects*; D019573:Epithelium, Corneal / Q000187:drug effects*; D005434:Flow Cytometry; D024841:Fluoroquinolones / Q000633:toxicity*; D006801:Humans; D008163:Luminescent Measurements; D000077266:Moxifloxacin; D011292:Premedication; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D001548:Benzalkonium Compounds; D024841:Fluoroquinolones; D017382:Reactive Oxygen Species; D013267:Stilbenes; D000077185:Resveratrol; D000077266:Moxifloxacin
keywords: ROS; corneal epithelium; cytotoxicity; moxifloxacin; resveratrol