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P. F. Kador, H. Jin, J. Randazzo, J. Makita; Mutifuctional Antioxidants for the Potential Treatment of Ocular Diseases. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3187.
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A number of ocular diseases including cataract and macular degeneration are associated with oxidative stress and the increased presence of iron which can participate in the generation of reactive oxygen species (ROS) through the Fenton reaction. The purpose of this study was to determine whether multifunctional antioxidants possessing both the ability to reduce Fe through chelation and decrease the presence of ROS through electron scavenging can be developed.
A series of novel compounds possessing chelating or antioxidant groups or both were synthesized. Chelation of Ca2+, Mg2+, Zn2+, Cu1+, Cu2+, Fe2+, and Fe3+ was determined by electrospray ionization mass spectrometry (ESI-MS). Free radical scavenging (antioxidant) activity was evaluated in the SRA-1 human lens epithelial cell line using 2',7'-dichlorodihydrofluorescein diacetate (DCF) stain for the detection of ROS generated by Fe2+ and hydrogen peroxide (Fenton reaction) and 10 mM homocysteine which induces ROS through endoplasmic reticular (ER) stress linked unfolded protein response (UPR).
Compounds possessing chelating groups selectively bound in order: Cu > Fe > Zn. No binding of Ca or Mg was observed. In the Fenton Reaction induced ROS, a dose dependent reduction in ROS staining was observed with compounds possessing chelating groups, antioxidant groups, or both. With homocysteine induced ROS, a dose dependent decrease in ROS was observed with only compounds possessing the antioxidant groups.
By selectively reducing Cu or Fe through chelation and also reducing ROS by scavenging electrons, these compounds appear to have promising therapeutic applications for ocular diseases such as cataract and macular degeneration.
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