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M.E. Mahmoud, E. de Juan, M. Cooney; Pharmacokinetics of Genistein Distribution in Blood and Retinas of Diabetic and Non-Diabetic Rats . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3594.
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Purpose: Genistein is a natural isoflavone abundant in soybean. This selective inhibitor of protein phosphotyrosine kinase is a key pathway of angiogenesis. Our group has demonstrated potent anti-angiogenic activity in the retina of experimental animals (e.g. Zucker diabetic rats) with oral administration of genistein. In the present study genistein pharmacokinetic and retinal tissue distributions were determined in normal and streptozotocin diabetic rats. Methods: An isocratic, reverse-phase C18 HPLC system was developed to measure genistein concentration in blood and retinal tissue. Genistein (99%) pharmacokinetic parameters were determined in Sprague-Dawley (SD) rats receiving an intravenous formulated dose of 5 mg/kg genistein. We collected blood samples from the retro-orbital plexus before genistein injection and 5, 10, 15, 30, and 60 min and 2 and 4 hr after injection. Steady-state concentration of genistein was determined in streptozotocin (80 mg/kg I.V.) diabetic and non-diabetic rats receiving 2 types of genistein (99%)-rich diet (150 and 300 mg/kg diet) for 10 days. Blood samples were collected on the tenth day, before the rats were sacrificed. The eyes were removed and the retinas were dissected and weighed. Blood samples were processed for HPLC measurement. Results: The decay of IV-administered genistein in SD rats exhibited a 2 compartmental open model. The T1/2 of the distribution and elimination phases were 2.09 ± 0.7 min and 71.79 ± 25 min respectively. The blood steady-state and retina concentrations of genistein in diabetic and non-diabetic SD rats after 10 days on a genistein-rich (150 or 300 mg/kg) diet are shown in the table. Conclusions: The blood steady-state concentrations of genistein were not significantly different for diabetic and non-diabetic rats. While the difference in retinal tissue concentration was significant ( p < 0.05) for both diets for both diabetic and non-diabetic rats, this difference could be due to the increased blood/eye permeability that occurs early in diabetics. View OriginalDownload SlideView OriginalDownload Slide
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