ABSTRACT
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
We newly prepared a unique one-side-coated insert that releases drug from only uncoated side. The purpose of this study is to determine whether ocular and systemic absorption of ophthalmic drug could be altered by an inserting direction of the insert in rabbit eyes. One-side-coated insert was prepared by attaching a polypropylene tape on the one side of the polymer disc of poly(2-hydroxypropyl methacrylate) (HPM) containing tilisolol as a model ophthalmic drug. The insert was applied in the lower conjunctival cul-de-sac of albino rabbits with the uncoated side facing bulbar conjunctiva/sclera (SC insert) or palpebral conjunctiva (CJ insert). At the adequate intervals, the tear fluid, plasma, aqueous humor, conjunctiva, and sclera were collected and the drug concentrations were determined by an HPLC. A release of tilisolol from the one-side-coated insert was twice slower than from the uncoated insert. Ocular application of the one-side-coated insert produced the constant concentrations of tilisolol in the tear fluid over 180 min. SC insert showed higher drug concentrations in the aqueous humor and sclera, and lower drug concentrations in the plasma and conjunctiva than CJ insert.The one-side-coated insert can alter the ocular and systemic absorption of drug by an inserting direction.
