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S. Kalakonda, K.R. Hegde, S.D. Varma; Induction of Apoptosis in Galactosemic lenses: Prevention by pyruvate. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1699.
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Purpose:Several studies suggest that induction of cataracts under hyperglycemia is initiated by a varied mix of membrane linked and cytosolic biochemical reactions such as polyol synthesis, oxidative stress and glycation etc. However, prevention and defense against these deleterious reactions as well as the maintenance of cellular differentiation process require an intact functioning DNA, which is necessary for proper transcription. Information on the effect of hyperglycemia on its structure in lens is highly lacking at present. The objective of this investigation was hence to determine if the DNA structure could be also adversely affected by the glycemic conditions, and if such an effect could be attenuated by pyruvate, an agent that has been shown by us to prevent sugar cataract formation as well as apoptosis. A preliminary communication to this effect is in press (Mol & Cell Biochem, 2004). Methods: Sprague dawley rats weighing 65–75 gm. were fed normal and galactose (30%) enriched diet, with and without pyruvate (2%). After eight days, the rats were euthanized, lenses isolated and used for detection of apoptosis by using TUNEL reaction. Also, tissue DNA was isolated, amplified through ligation mediated PCR and separated by electrophoresis on agarose gel for detection of ladder. Results: The number of TUNEL positive cells were significantly greater in the galactosemic lenses, as compared to the normal. Also, electrophoresis of the LM–PCR amplified DNA samples demonstrated a definite laddering pattern. Interestingly these changes were inhibited in lenses from pyruvate fed animals. Conclusions: The results demonstrate that cataract induction caused by glycemia involves not only the membrane and cytosolic biochemical reactions mentioned above but also involves DNA fragmentation. The inhibitory effect of pyruvate against apoptosis has been demonstrated for the first time. Mechanism of this effect remains to be studied.
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