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S.D. Varma, K.R. Hegde; Induction of Cataract by Sodium Selenite: Prevention by –Ketocarboxylates . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2647.
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Purpose: Excessive generation of reactive oxygen species (ROS) is involved in the pathogenesis of ageing diseases including cataracts. We have shown that the formation of such cataracts can be prevented by antioxidants such as ascorbate. Pyruvate, an endogenous metabolite has also been shown to be effective. The pyruvate effect could be attributed to its oxyradical scavenging properties and to its ability to accelerate glycolysis and to facilitate ATP generation. Currently we examined if other α–ketoacids, that have insignificant effect on glycolysis but are yet effective ROS scavengers can also be useful. Results described herein are in accordance with this hypothesis. Methods: Cataract was induced in rat pups by intraperitoneal injections of sodium selenite (controls). The experimental groups received, in addition, α–KG. Presence of cataracts was initially ascertained by pen–light and documented by slit lamp photography. Lenses were then isolated and photographed through a grid for further assessment of cataract severity. The damage to the lens was further assessed biochemically by their levels of ATP and GSH. Results: 76% of the eyes in the selenite controls developed advanced cataracts, only 23% of the eyes developed cataracts in the group treated with sodium selenite and α–KG. Cataracts were initially nuclear, extending subsequently to the cortex. The lenses were clearer in the α–KG treated group. The grid pattern was highly distorted and obscured when viewed through the selenite controls, while it was only feebly distorted through the lenses of α–KG treated animals. ATP in the normal and selenite controls were 1501±250 and 700±120 nanomoles/g lens weight, respectively. It was1344±200 nanomoles/g in the experimental group treated with selenite and α–KG. GSH levels in the normal and selenite controls were 2.4±0.2 and 1.6±0.2 µmoles/g, respectively. The latter decrease was prevented in the rats treated with α–KG, the level in this case being 2.4±0.1µmoles/g. Conclusions: The results demonstrate that α–ketoacids such as pyruvate and α–KG could exert their anti–cataractogenic effect primarily by virtue of the presence of α–keto carboxyl group, acting as scavengers of ROS. α–KG and other similar oxo–acids are envisaged also to be therapeutically more useful due to their greater stability as well as the generation of acids with lower ionization. These properties are therefore considered suitable from the pathophysiological as well as pharmacological points of view.
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