A Stevens1. 1. National Vision Research Institute of Australia, Carlton, Australia.
Abstract
BACKGROUND: Recent data have favored non-enzymatic glycation as a likely mechanism in diabetic cataract formation. The advanced glycation end products (AGEs) that are formed lead to opacification of the lens by disrupting the short-range order between the proteins. Attempts to decrease AGE formation has led to the use of various anti-glycating agents. Their efficacy, however, has been questionable. METHODS: The extent of AGE formation was monitored in fetal bovine eyes using non-tryptophan fluorescence. The amount of carbohydrate bound to the proteins was measured after reduction with radio-labelled sodium borohydride. RESULTS: While the addition of glucose, glucose-6-phosphate or fructose increased the levels of glycation by only 25 percent and the levels of AGEs by 40 percent, glyceraldehyde resulted in a 70 percent increase in glycation and showed extensive AGE formation (an increase of over 6600 percent when compared to the unglycated protein). The anti-glycating agents aspirin and ibuprofen were unable to significantly decrease the extent of bound metabolite or reduce the amount of AGE formed. In contrast, penicillamine and aminoguanidine were more effective in reducing the levels of AGEs, even though the levels of bound metabolite appeared unchanged. CONCLUSIONS: Triose phosphates are likely to be the major metabolic intermediates that result in AGE formation. The anti-glycating agents, whereas penicillamine and aminoguanidine-which react with the Amadori-derived fragmentation products-significantly decreased levels of AGEs.
BACKGROUND: Recent data have favored non-enzymatic glycation as a likely mechanism in diabetic cataract formation. The advanced glycation end products (AGEs) that are formed lead to opacification of the lens by disrupting the short-range order between the proteins. Attempts to decrease AGE formation has led to the use of various anti-glycating agents. Their efficacy, however, has been questionable. METHODS: The extent of AGE formation was monitored in fetal bovine eyes using non-tryptophan fluorescence. The amount of carbohydrate bound to the proteins was measured after reduction with radio-labelled sodium borohydride. RESULTS: While the addition of glucose, glucose-6-phosphate or fructose increased the levels of glycation by only 25 percent and the levels of AGEs by 40 percent, glyceraldehyde resulted in a 70 percent increase in glycation and showed extensive AGE formation (an increase of over 6600 percent when compared to the unglycated protein). The anti-glycating agents aspirin and ibuprofen were unable to significantly decrease the extent of bound metabolite or reduce the amount of AGE formed. In contrast, penicillamine and aminoguanidine were more effective in reducing the levels of AGEs, even though the levels of bound metabolite appeared unchanged. CONCLUSIONS: Triose phosphates are likely to be the major metabolic intermediates that result in AGE formation. The anti-glycating agents, whereas penicillamine and aminoguanidine-which react with the Amadori-derived fragmentation products-significantly decreased levels of AGEs.