Non-enzymatic glycation of lens proteins and haemoglobin-inhibition by pyruvate: an in-vivo study.

Abstract

Previous studies have demonstrated that pyruvate can prevent protein glycation and oxidative stress under in-vitro conditions. The aim of this study was to examine the in-vivo effectiveness of this metabolite against glycation of lens crystallins and haemoglobin in galactosemic rats. Sprague-Dawley rats were maintained on a 30% or 50% galactose-containing diet in the absence or presence of 2% or 5% pyruvate in food and water, respectively. The animals were killed subsequently and the extent of glycation of lens crystallins and haemoglobin was determined using an affinity column chromatograpic technique. Maintenance of rats on the high galactose diet resulted in a significant increase in glycation of both the proteins. The increase was faster and more substantial in the animals maintained on the 50% galactose diet than that in the animals fed a 30% galactose diet. The increase in the latter was also very significant. Supplementation with pyruvate inhibited the process. The inhibition is attributable to a competitive binding of pyruvate to the protein NH2 groups as well as to the antioxidant effect of the compound. The studies therefore suggest that this and other alpha-keto-acids may be physiologically useful in minimizing glycation and oxidative stress induced tissue pathology by the hyperglycaemic conditions, such as diabetes and galactosemia. The results are also considered pharmacologically significant.