Effect of alpha-ketoglutarate against selenite cataract formation.

We have previously shown that pyruvate protects against reactive oxygen species (ROS) induced damage to lens in vitro. It has also a significant effect against cataract development. Its effectiveness has been ascribed to the presence of alpha-keto-carboxylate group in the molecule, acting as a scavenger of ROS. Hence, it was felt desirable to determine if other alpha-keto-acids could have similar effects. These studies have hence been conducted with alpha-ketoglutarate (alpha-KG), a compound with greater stability and without any known significant effect on the glycolysis. Its effectiveness has been assessed by monitoring cataract development in rat pups given sodium selenite. A large percentage of such animals (about 80%) developed nuclear opacity 7-8 days after its administration. In animals treated with alpha-ketoglutarate, the incidence of cataracts was only 23%. The agent therefore has a very substantial anticataractogenic effect, as apparent by direct slit lamp examination followed by photography, as well as by examination of the isolated lenses through transillumination. The significance of the ophthalmologic findings was apparent also by better physiological maintenance of the tissue, reflected by higher levels of ATP and GSH. In view of these in vivo beneficial effects, studies are in progress to identify the biochemical and metabolic sites of its action. Whether the effectiveness is related only to its action as a ROS scavenger or it could be contributed also by some metabolic effects independent of ROS remains to be determined.