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L. Zhu, A. Laabich, D. Leung, C. Bavik, R. Kubota, A. Fawzi; Protective Effect of Myricetin and Related Flavonols Against Light-Induced Retinal Damage in Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2493.
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Flavonoids have long been known as hydrogen-donating free radical scavengers and free radical formation suppressors. We have reported in Laabich A. et al. (ARVO abstract, 2007) that myricetin, a member of the flavonols family of flavonoids, was protective against light induced photoreceptor cell death in primary retinal cell culture. This study was performed to investigate the structure-activity relationship of myricetin and related flavonols with different hydroxyl substitution in protecting retinal cells from light-induced damage in vivo.
All research was conducted in compliance with the "ARVO Statement for the Use of Animals in Ophthalmic and Vision Research". Ten BALB/c mice (7-8 weeks old) per group were dosed at 50 mg/kg (myricetin, quercetin, or kaempferol) by intraperitoneal injection and exposed to 8000 lux white fluorescent light for 1 hour. The treated mice were then kept in dark until the retinas were harvested 36 hours later for apoptosis analysis or kept in cyclic light for another 2 weeks in the case of morphometric studies. Nucleosome release of apoptotic retinal cells was examined using cell death detection ELISA kits. Sections along the vertical meridian were collected for retinal morphology and photoreceptor morphometry. Unexposed and light-exposed BALB/c mice of the same age served as control.
Myricetin treatment of mice produced a dose-dependent protection of the retina against light-induced retinal damage. The dose-dependent effect was steep showing an ED50 of 27 mg/kg and full protection at 50 mg/kg. Quercetin treatment showed 45% protection at 50mg/kg. In contrast, kaempferol was inactive.
The flavonols showed increasing potency in protecting retinal cells from light damage both in vitro and in vivo as the hydroxyl group substitution on the B ring increases, myricetin>quercetin>kaempferol. This study not only provides insights for the potential potency of certain flavonoids in protecting the retina from light damage, but also serves as a validation for our in-vitro assay being a reliable way in screening potential drug candidates that protect retinal cells against light damage.
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