ABSTRACT
AIM: The aim of this study was to examine the usefulness of an electrophysiologic method for predicting corneal epithelial breakdown by antiallergic eyedrops and comparing the results with those in other appraisal methods. METHODS: Six kinds of antiallergic eyedrops, including benzalkonium chloride (BK) as an ophthalmic preservative and two kinds of BK-free antiallergic eyedrops, were used in this study. Eyedrops were applied to excise rabbit corneas and monitoring was performed according to an electrophysiologic method, using a commercially available chamber system to mimic human tear turnover. Changes in transepithelial electrical resistance (TEER) in the corneal surface were recorded. The cytotoxicity of each kind of eyedrops in a normal rabbit corneal epithelial (NRCE) cell line and a human endothelial cell line EA.hy926 was also examined. RESULTS: The extent of decrease in the corneal TEER after applying antiallergic eyedrops was dependent on the concentration of the BK included as a preservative, but it was also affected by the different kinds of drugs when the BK concentration was low. Higher cytotoxicity of the eyedrops against the NRCE and EA.hy926 cell lines was observed with a reduction of TEER. CONCLUSIONS: Monitoring changes in the corneal TEER, according to the electrophysiologic method with the application of antiallergic eyedrops, is useful for predicting corneal epithelial breakdown caused by their instillation.
Subject(s)
Anti-Allergic Agents/administration & dosage , Anti-Allergic Agents/pharmacology , Blood-Retinal Barrier/drug effects , Epithelium, Corneal/drug effects , Animals , Benzalkonium Compounds/pharmacology , Cell Line , Chemistry, Pharmaceutical , Diffusion Chambers, Culture , Electric Impedance , Electrophysiology , In Vitro Techniques , Male , Ophthalmic Solutions , Preservatives, Pharmaceutical , RabbitsABSTRACT
We investigated the effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, pravastatin and fluvastatin, on the induction of micronuclei by ionizing radiation or bleomycin in Chinese hamster ovary cells in order to assess the radical-scavenging ability of these inhibitors. The results indicated that both pravastatin and fluvastatin had no effect on the induction of micronuclei by X-irradiation when they were applied for either pre-treatment or post-treatment. In contrast, both drugs effectively reduced the frequency of bleomycin-induced micronuclei when they were applied for simultaneous treatment or post-treatment, but not for pre-treatment. This indicates that the radical-scavenging ability of these two HMG-CoA reductase inhibitors differs according to the origins of the radicals--e.g., X-rays or bleomycin--even when the two drugs are compared at an equivalent cytotoxic dose. Our results suggest that both pravastatin and fluvastatin have the ability to scavenge certain types of radicals and to protect cells against oxidative stress.
Subject(s)
Bleomycin/adverse effects , Fatty Acids, Monounsaturated/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Indoles/administration & dosage , Micronuclei, Chromosome-Defective/drug effects , Micronuclei, Chromosome-Defective/radiation effects , Pravastatin/administration & dosage , X-Rays/adverse effects , Animals , CHO Cells , Cricetinae , Cricetulus , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Drug Interactions , Fluvastatin , Micronuclei, Chromosome-Defective/chemically induced , Radiation Dosage , Radiation Tolerance/radiation effectsABSTRACT
The aim of this study was to investigate the postmortem changes of concentrations of triazolam and diazepam in the rat model and to confirm the factor causing the phenomenon. We administered triazolam or diazepam orally to rats and then sacrificed them 1 h after administration. Abdominal tissues including stomach content and small intestine, thigh muscle and heart blood were collected at 0, 12, 24 h after death, and postmortem changes of the two drug concentrations were compared. Drug concentrations in the samples were analyzed by a selected ion monitoring of gas chromatography/mass spectrometry. Gastrointestinal postmortem concentrations of triazolam and diazepam decreased. On the other hand, the drug concentrations in the liver and kidney increased markedly, and those in lung and heart blood increased slightly during postmortem periods by diffusion from the gastrointestinal tract. The patterns of both drug concentration changes were similar. However, the extent of the triazolam increase tended to be larger than that of diazepam. This difference may be accounted for by lower triazolam concentrations before death. The postmortem drug concentrations of thigh muscle did not change when administered with triazolam and diazepam. For both triazolam and diazepam, a significant correlation was observed in the drug concentration between the small intestine and the kidney at 24 h after death, indicating that major cause of the change in the drug concentration in the kidney was diffusion from the small intestine up to 24 h after death. The results in this study indicate that diazepam as well as triazolam diffuses from the gastrointestinal tract into the surrounding tissues after death and suggest that the diffusion is influenced by their pharmaceutical properties before death.
