Effect of the pyridoindole antioxidant stobadine on developmentof experimental diabetic cataract and on lens protein oxidation in rats:comparison with vitamin E and BHT

[摘要] Purpose: The aim of this study was to investigate the effect ofdietary supplementation with the pyridoindole antioxidant stobadine onthe development of diabetic cataract in rats. The findings were comparedwith the effect of the natural antioxidant vitamin E and the well knownphenolic synthetic antioxidant butylated hydroxytoluene.Methods: Streptozotocin induced diabetic male Wistars rats were fedfor 18 weeks a standard diet or a diet supplemented with stobadine(0.05% w/w), vitamin E (0.1% w/w), butylated hydroxytoluene (BHT, 0.4%w/w), or a mixture of stobadine (0.05% w/w) and vitamin E (0.1% w/w).The progress of cataract was monitored biweekly by ophthalmoscopicinspection. Plasma glucose and body weight were recorded regularly. Atthe end of the experiment, the content of free sulfhydryl and carbonylwas determined in total lens proteins and in the stobadine group plasmalevels of malondialdehyde were also measured.Results: Long term treatment of diabetic animals with stobadine(STB), vitamin E, or BHT led to a marked delay in the development ofadvanced stages of cataract. At the end of the experiment, the visualcataract score was significantly decreased in the diabetic groupstreated with stobadine or BHT, while vitamin E had no significanteffect. Unexpectedly, combined treatment with STB+vitamin E advanced theprogression of the higher stages of cataract, though without affectingthe overall visual cataract score. Neither of the antioxidants exertedan effect on the glycemic state or body weight of the animals.Biochemical analyses of eye lens proteins showed significant diminutionof sulfhydryl groups and elevation of carbonyl groups in diabeticanimals in comparison to healthy controls. Dietary supplementation withany of the antioxidants studied did not influence the levels of thesebiomarkers significantly. Nevertheless, in diabetic animals, stobadinesupplementation significantly attenuated plasma levels ofmalondialdehyde, an index of systemic oxidative damage.Conclusions: The results are in accordance with the postulatedpro-oxidant role of chronic hyperglycemia, however, the direct oxidativefree radical damage of eye lens proteins does not seem to be the keymechanism effective in the development of diabetic cataract. Sugarcataractogenesis appears to be a complex process, in which multiplemechanisms may be involved, including consequences of the overtoxidative stress in diabetes (e.g., protein modifying potential of toxicaldehydes generated as byproducts of carbohydrate autoxidation and lipidperoxidation). The ability of stobadine to attenuate lipoxidationreactions in diabetes may account, at least partly, for its observedanticataract action. Mechanisms involving reduction of mitochondrialdamage by stobadine are also discussed.

[学科分类] 生物化学/生物物理