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S.D. Varma, K.R. Hegde, M.G. Henein; Protective Effect of Pyruvate Against Oxidative Stress and Cataract Formation in Mouse Lens . Invest. Ophthalmol. Vis. Sci. 2003;44(13):318.
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Purpose: We have previously shown that pyruvate protects rat lens against oxidative stress. This could be attributable to its direct oxyradical scavenging properties as well as to several of its metabolic effects involved in maintaining lens clarity. Further studies, using the lens of another species were hence desired. These studies were done with mouse lens model, wherein the pace of cataract resembles that in humans, contrary to that in rat model. Further study was also desired because of the ability of pyruvate to inhibit sorbitol formation considered to play a major role in the rat lens metabolism. Hence, we have studied the effectiveness of pyruvate in preventing ROS damage to mouse lens in vitro as well as in preventing formation of diabetic cataracts in vivo. Methods: The effectiveness of pyruvate against direct oxidative stress was evaluated by organ culture where the lenses were incubated in ROS generating medium. The damage was assessed on the basis of the status of cation transport activity of the lenses. Its effectiveness against cataract formation in vivo was studied by maintaining experimentally diabetic mice on pyruvate-supplemented diet and monitoring cataract formation ophthalmoscopically and biochemically. Results: Incorporation of pyruvate in the culture medium was found to protect the lens against oxidative stress as measured by its ability to transport 86Rb+ against a concentration gradient. The protective effect was also apparent by better maintenance of the levels of GSH and ATP, as well as by better clarity of the tissue. The incidence of cataracts at the end of 4 months in the pyruvate fed diabetic group was only about 57%, while it was about 82% in the control diabetic mice. Biochemically there was a significant drop in GSH levels and an increase in the level of glycated protein in the untreated diabetic group. In the group treated with pyruvate, the GSH level was maintained nearly normal. The extent of glycation also did not increase, contrary to the untreated group. Conclusions: The results demonstrate that pyruvate could be effective in preventing cataract formation in situations involving direct oxidative stress as well as in diabetic situations where several deleterious factors are operative. Since pyruvate is an endogenous compound, the findings are considered to be of therapeutic significance. These findings also suggest that the pyruvate effect has significance over a wider range of species than originally thought.
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