Purpose: Advanced glycation end products (AGEs) play an important role in protein modification during cataract formation. Along with sugars, α-dicarbonyl compounds, such as methylglyoxal (MGO), have been implicated in AGE formation. Here we report the effect of pyridoxamine (PM) on AGEs and AGE-precursor-metabolizing enzymes in diabetic rat lenses and organ-cultured rat lenses. Methods: Diabetes was induced in rats by injecting streptozotocin. Diabetic and nondiabetic control rats were treated with PM in drinking water for 20 weeks. Rat lenses were organ cultured with normal or high glucose. We measured lens glutathione (GSH), MGO, AGEs and activities of aldose reductase and glyoxalase I. Results: Treatment of diabetic rats with PM inhibited both argpyrimidine and pentosidine formation when compared to untreated diabetic animals and nondiabetic control animals. Incubation of lenses with 30 mM D- glucose caused an elevation of these AGEs. Addition of 250 µM PM along with glucose resulted in inhibition of AGE formation in organ-cultured lenses. The glyoxalase I activity was significantly reduced in diabetic rats; PM treatment inhibited such a reduction. The activity of aldose reductase was elevated in diabetic lenses; PM treatment further enhanced its activity. Conclusion: Our results suggest that PM can inhibit AGE formation in the diabetic lens by enhancing the activity of aldose reductase and reacting with precursors of AGEs.

Keywords:
Glycation, Cataract, Dicarbonyls, Advanced glycation end products, Pyridoxamine, Diabetes, rats
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© 2006 S. Karger AG, Basel
2006
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