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虹鳟鱼晶状体的体外亚急性致白内障研究。

In vitro subacute cataractogenic study in rainbow trout lens.

作者信息

Hikida M, Iwata S

机构信息

Department of Biophysical Chemistry, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.

出版信息

J Pharmacobiodyn. 1987 Sep;10(9):443-8. doi: 10.1248/bpb1978.10.443.

Abstract

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.

摘要

虹鳟鱼的晶状体可在0摄氏度的H10培养基中孵育2.5个月,而不会失去透明度,阳离子水平也不会改变。研究了该晶状体孵育系统在药物毒性测试中的适用性。当晶状体用二酰胺、对氯汞苯甲酸(PCMB)、N-乙基马来酰亚胺(NEM)、1,2-萘醌、哇巴因和缬氨霉素处理时,检测了随着晶状体浑浊化而发生的阳离子和谷胱甘肽(GSH)水平变化以及乳酸生成情况。在生化参数中,Na+-K+比率(Na+/K+)的增加与晶状体浑浊化关系最为密切,这与哺乳动物晶状体的情况相同。通过肉眼观察到了晶状体浑浊化。因此,Na+/K+被用作药物的晶状体毒性参数。就导致Na+/K+增加的最低浓度(1.0×10-10 M)而言,缬氨霉素被发现是最有效的药物。另一方面,用2.5×10-5 M NEM处理的晶状体在2.5个月内Na+/K+既没有变化,透明度也没有丧失。在虹鳟鱼晶状体中,二酰胺、PCMB、缬氨霉素和哇巴因导致的晶状体毒性在比小鼠晶状体低1000倍的浓度下即可检测到。通过使用在0摄氏度下孵育的虹鳟鱼晶状体,可以通过明确的生化参数来表征药物毒性,并且可以在较低浓度下长时间观察到。因此,虹鳟鱼晶状体对于研究长期药物毒性和晶状体浑浊化机制非常有用。

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