title: Fisetin and luteolin protect human retinal pigment epithelial cells from oxidative stress-induced cell death and regulate inflammation.
abstract: Degeneration of retinal pigment epithelial (RPE) cells is a clinical hallmark of age-related macular degeneration (AMD), the leading cause of blindness among aged people in the Western world. Both inflammation and oxidative stress are known to play vital roles in the development of this disease. Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation. We also compare the growth and reactivity of human ARPE-19 cells in serum-free and serum-containing conditions. The absence of serum in the culture medium did not prevent ARPE-19 cells from reaching full confluency but caused an increased sensitivity to oxidative stress-induced cell death. Both fisetin and luteolin protected ARPE-19 cells from oxidative stress-induced cell death. They also significantly decreased the release of pro-inflammatory cytokines into the culture medium. The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1. The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD.
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.B. 1627, FI-70211, Kuopio, Finland.|Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O.B. 1627, FI-70211 Kuopio, Finland.
authors.forename: Maria
authors.initials: M
authors.lastname: Hytti
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.B. 1627, FI-70211, Kuopio, Finland.|Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O.B. 1627, FI-70211 Kuopio, Finland.
authors.forename: Niina
authors.initials: N
authors.lastname: Piippo
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.B. 1627, FI-70211, Kuopio, Finland.|Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O.B. 1627, FI-70211 Kuopio, Finland.
authors.forename: Eveliina
authors.initials: E
authors.lastname: Korhonen
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.B. 1627, FI-70211, Kuopio, Finland.
authors.forename: Paavo
authors.initials: P
authors.lastname: Honkakoski
authors.affiliation: Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O.B. 1627, FI-70211 Kuopio, Finland.|Department of Ophthalmology, Kuopio University Hospital, P.O.B. 100, FI-70029 KYS, Finland.
authors.forename: Kai
authors.initials: K
authors.lastname: Kaarniranta
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.B. 1627, FI-70211, Kuopio, Finland.|Department of Ophthalmology, Kuopio University Hospital, P.O.B. 100, FI-70029 KYS, Finland.
authors.forename: Anu
authors.initials: A
authors.lastname: Kauppinen
mesh_terms: D016923:Cell Death; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology
chemical_list: D005419:Flavonoids; D044948:Flavonols; D047311:Luteolin; C017875:fisetin