In vitro subacute cataractogenic study in rainbow trout lens.
Crystalline lens of rainbow trout can be incubated in H10 medium at 0 degrees C for 2.5 months without loss of transparency and change in cation level. Applicability of this lens incubation system to test for drug toxicity was investigated. Changes in cation and glutathione (GSH) levels and lactic acid production which occurred with opacification were examined when the lens was treated with diamide, p-chloromercuribenzoic acid (PCMB), N-ethylmaleimide (NEM), 1,2-naphthoquinone, ouabain and valinomycin. Among biochemical parameters, the increase in Na+-K+ ratio (Na+/K+) was most closely related to lens opacification, as in mammalian lenses. Lens opacification was observed macroscopically. Therefore, Na+/K+ was used as a lens toxicity parameter of the drug. Valinomycin was found to be the most effective drug as measured by the lowest concentration (1.0 X 10(-10) M) which gave an increase in Na+/K+. On the other hand, the lens treated with 2.5 X 10(-5) M NEM demonstrated neither change in Na+/K+ nor loss of transparency for 2.5 months. Lens toxicities due to diamide, PCMB, valinomycin and ouabain were detectable in the rainbow trout lens at 1000 times lower concentrations than those in the mouse lens. By using rainbow trout lenses incubated at 0 degrees C, drug toxicity can be characterized by well-defined biochemical parameters and can be observed at lower concentrations for long periods of time. The rainbow trout lens is, therefore, very useful for studying long-term drug toxicity and the lens opacification mechanism.
Department of Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
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Hikida
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Iwata
D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D002386:Cataract / Q000139:chemically induced* / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D014337:Trout
D000477:Alkylating Agents; D002412:Cations; D007773:Lactates; D013438:Sulfhydryl Compounds; D005978:Glutathione