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K. Hegde, S. Varma, S. Kovtun; Effectiveness of Pyruvate in Reversal of Tissue Damage by Oxidative Stress – Implication in Clinical Therapy of Cataracts . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4324.
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Oxidative stress with aging and clinical conditions such as diabetes constitutes a strong cataractogenic factor, evident by the prevention and attenuation of cataracts by pyruvate (PY) administration coincident with the onset of diabetes in rodents. However, in view of the belated detection of cataracts in humans, it was desirable to determine effectiveness of PY, if any, in reversing early oxidative lens damage in vitro and examine its possible effectiveness in reversing and attenuating cataractous changes in vivo.
Mice lenses were cultured in medium 199 without or with reactive oxygen species (ROS) generated by Xanthine/Xanthine oxidase system. The damage was assessed in terms of the rubidium transport (distribution ratio between lens water, CL, and medium, CM), ATP and GSH etc. After a 50% decrease in the transport (∼2 hrs), PY or Ethyl PY was added to the medium and incubation continued further for 2 hrs. Controls were run without PY but in presence of ROS. Basal controls were also run without ROS and PY. In vivo, cataract reversal was assessed ophthalmoscopically and by fluorescein permeability of the isolated lenses.
The (CL/CM) in the basal controls was 14 at 2 hrs. GSH was 4.35 µmoles/g. With ROS, they decreased to 7, and 2.7. With the addition of pyruvate coincident with this damage, and continuation of incubation for another 2 hrs, the CL/CM increased to 16 with a corresponding increase in GSH to 2µmoles/g, but with continued fall without PY, the CL/CM and GSH being 4 and 1 respectively. In diabetic mice, cataract was perceptible by equatorial ring with enhanced fluorescence by 24 days after diabetes onset. Treatment with Ethyl PY eye drops starting even at this time, showed no increase in fluorescence, rather it reverted to the normal. The lenses of untreated group continued to develop advanced cataract and fluorescence.
The results strongly suggest that PY and PY Ester are effective in reversing early ROS induced physiological changes, and in reversing, attenuating as well as delaying cataractogenesis even on delayed treatment. The results are consistent with the hypothesis that treatment with PY, its ester or other anti–oxidants and metabolic agonists are potentially useful in delaying cataract formation when used prophylactically or even after cataract initiation.
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