Near-Total Glutathione Depletion and Age-Specific Cataracts Induced by Buthionine Sulfoximine in Mice

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Abstract
The specific inhibitor of glutathione biosynthesis, L-buthionine sulfoximine (L-BSO), although relatively nontoxic in adult mice, induces severe glutathione depletion and age-specific pathological changes when repeatedly administered to male suckling mice. Dense cataracts developed when mice aged 9 to 12 days were given a series of injections of L-BSO, despite excellent survival and the absence of other significant long-term effects. By contrast, similar treatment of mice aged 14 to 17 days, although slightly less effective in reducing glutathione levels, resulted frequently in death, hind-leg paralysis, or impaired spermatogenesis, but did not produce cataracts. Administration of L-BSO to preweanling mice provides a novel model system for the induction of cataracts by depletion of lens glutathione and may enable the study of critical functions of glutathione in the lens and other growing tissues during early postnatal development.