ABSTRACT
To determine the cytotoxicity of antibiotic eyedrops to ocular surface cells using a semi-quantitative method, a range of commercially available antibiotic eyedrops were assessed by using three corneal cell lines and one conjunctival cell line. All antibiotic solutions were free of benzalkonium chloride. Cell viability was determined by the MTT assay and neutral red assay following the exposure of cells to the undiluted, 2- and 10-fold diluted drugs for 10, 30, and 60 min. Toxicity was compared using % cell viability score (%CVS) . The tested eyedrops and values of %CVS50 and %CVS40/80 were Bestron(®) (cefmenoxime, 100, 94) , Panimycin(®) (dibekacin, 86, 58) , Noflo(®) (norfloxacin, 90, 50) , Cravit(®) (levofloxacin, 86, 46) , Tosfulo(®) (tosufloxacin, 57, -3) , and Vigamox(®) (moxifloxacin, 57, -6) . Cell viability markedly increased after dilution. For instance, cell viability assayed by MTT was > 80% for all the measurements in antibiotics diluted 10-fold, and the rate of the measurements showing > 80% cell viability decreased to 43% (31 out of 72 measurements) in the solutions diluted 2-fold. Of the drugs tested, Bestron(®) containing cefmenoxime showed the weakest toxicity. Vigamox(®) containing moxifloxacin and Tosuflo(®) containing tosufloxacin were more toxic when compared with the other antibiotics. CVS was useful for the comparison of the cytotoxicity of the drugs.
Subject(s)
Anti-Bacterial Agents/toxicity , Conjunctiva/drug effects , Cornea/drug effects , Ophthalmic Solutions/toxicity , Animals , Aza Compounds/toxicity , Cefmenoxime/toxicity , Cell Line , Cell Survival/drug effects , Conjunctiva/cytology , Cornea/cytology , Dibekacin/toxicity , Dose-Response Relationship, Drug , Epithelial Cells/drug effects , Fluoroquinolones/toxicity , Humans , Levofloxacin , Moxifloxacin , Naphthyridines/toxicity , Norfloxacin/toxicity , Ofloxacin/toxicity , Preservatives, Pharmaceutical , Quinolines/toxicity , RabbitsABSTRACT
Before introducing new antibiotics for corneal organ culture solutions, information about the endothelial cell toxicity is necessary. Therefore, we preserved 132 pig corneas in minimum essential medium with 2% fetal calf serum and 5% dextran T 500 and added 50, 100, 250 and 500 micrograms/cm3 cefmenoxime. Slight endothelial cell damage occurred at a concentration of 100 micrograms/cm3. Damage to endothelial cells was demonstrated by the inhibited uptake of fluorescein diacetate and by other staining procedures. 30% of the substance remained stable during a 10-day culture period as demonstrated by an HPLC method.
Subject(s)
Cefmenoxime/toxicity , Endothelium, Corneal/drug effects , Animals , Biological Transport/drug effects , Cell Survival , Cornea , Culture Media , Dose-Response Relationship, Drug , Endothelium, Corneal/metabolism , Endothelium, Corneal/pathology , Fluoresceins/metabolism , Necrosis , Organ Culture Techniques , Organ Preservation , SwineABSTRACT
The semisynthetic third generation cephalosporin cefmenoxime was injected through the pars plana into the mid-vitreous in seven rabbit eyes. The drug dosage varied between 0.5 and 15 mg. Seven control eyes were injected only with 0.9% NaCl-solution. Electroretinography was performed before injection and 1 week post injection. The rabbits were anesthetized by intramuscular application of ketanine (Ketanest). Immediately after the second ERG the eyes were enucleated and prepared for both light and electron microscopy. Light microscopy showed only slight retinotoxic effects. Electron microscopy revealed beginning toxic necrosis of the outer segments of the photoreceptors following drug doses equal to or greater than 2 mg. Significant changes in the ERG were not noted in any of the treated eyes. The toxicity of cefmenoxime and other cephalosporins reported in the literature is discussed together with the clinical relevance of the findings.
