Premium
The Effect of Quercetin in Cultured Human RPE Cells under Oxidative Stress and in Ccl2/Cx3cr1 Double Deficient Mice
Author(s) -
Cao Xiaoguang,
Tuo Jingsheng,
Shen Defen,
Liu Melissa,
Chan ChiChao
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.753.4
Subject(s) - quercetin , apoptosis , oxidative stress , retinal , inflammation , pharmacology , chemistry , intraperitoneal injection , lipid peroxidation , microbiology and biotechnology , immunology , biology , antioxidant , biochemistry
PURPOSE To investigate mechanisms for the protective effects of quercetin in cultured human retinal pigment epithelium (RPE) cells and in Ccl2 −/− /Cx3cr1 −/− (DKO) mice, which spontaneously develop retinal lesions mimicking the characteristics of age‐related macular degeneration. METHODS Cultured ARPE‐19 cells were exposed to 1mM H 2 O 2 with or without 50μM quercetin for 2 hours. DKO and C57/B6 (WT) mice were treated with 25mg/kg/day quercetin via intraperitoneal injection for two months. RESULTS Quercetin protected RPE cells from H 2 O 2 ‐induced injury, increased the Bcl‐2/Bax transcript ratio, decreased Bax, FADD , Caspase‐3, − 9, TNF‐α, iNOS and COX‐2 mRNA levels, and lowered COX and NO levels. DKO mice had a lower antioxidative capacity, higher serum NO, COX and PGE2 levels, and higher ocular bax and caspase3 mRNA levels. Quercetin decreased serum oxidative and inflammatory molecules but not ocular pro‐apoptotic or pro‐inflammatory transcript levels; the retinal lesions in the DKO mice remained unaffected. CONCLUSIONS Quercetin protects human RPE cells from oxidative stress in vitro by directly inhibiting the apoptosis pathway and exerting anti‐inflammatory effects. Quercetin has no effect on retinal lesions in DKO mice due to insufficient suppression of ocular apoptosis or inflammation. The study was supported by the Intramural Research Program of the National Eye Institute, NIH.