Acute Effects of Indomethacin on Mitochondrial Function and Glutathione Levels in the Mouse Lens in Organ Culture

• Purpose, Experiments were carried out to study the effects of indomethacin on markers for oxidative damage and mitochondrial function in the intact mouse lens. Methods, Mouse lenses were incubated with fluorogenic indicator dyes prior to administration of 50 {micro}M indomethacin. The response was monitored, in real time, for several hours. Mitochondrial depolarization was followed by preloading the lens with Rhodamine 123 (10 {micro}g/ml). Peroxide production was studied in lenses loaded with 50{micro}M DCF-DA and superoxide levels with 10 {micro}M hydroethidium. Glutathione levels were assayed with 50 {micro}M monochlorobimane following short-term administration of indomethacin. Results, No significant changes in the production of peroxide or superoxide were found up to 3 hours after administration of indomethacin. The level of reduced glutathione was reduced by approximately 10 percent 3 h after drug administration. There was a significant increase (20%) of mitochondrial depolarization, compared to control lenses, one hour following indomethacin administration. Conclusions, The frequent use of nonsteroidal anti-inflammatory drugs in ophthalmology necessitates a close examination of effects besides the anti-inflammatory ones. This study points to relatively rapid effects on mitochondrial function and glutathione levels in the cultured mouse lens. The possible relation between these changes and the development of cataract remains to be studied.

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MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

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