title: Quercetin alleviates 4-hydroxynonenal-induced cytotoxicity and inflammation in ARPE-19 cells.
abstract: Retinal pigment epithelium (RPE) plays the principal role in age-related macular degeneration (AMD), a progressive eye disease with no cure and limited therapeutical options. In the pathogenesis of AMD, degeneration of RPE cells by multiple factors including increased oxidative stress and chronic inflammation precedes the irreversible loss of photoreceptors and central vision. Here, we report that the plant-derived polyphenol, quercetin, increases viability and decreases inflammation in stressed human ARPE-19 cells after exposure to the lipid peroxidation end product 4-hydroxynonenal (HNE). Several previous studies have been conducted using the direct oxidant H2O2 but we preferred HNE since natural characteristics predispose RPE cells to the type of oxidative damage evoked by lipid peroxidation. Quercetin improved cell membrane integrity and mitochondrial function as assessed in LDH and MTT tests. Decreased production of proinflammatory mediators IL-6, IL-8, and MCP-1 were indicated at the RNA level by qPCR and at the protein level by the ELISA technique. In addition, we probed the signaling behind the effects and observed that p38 and ERK MAPK pathways, and CREB signaling are regulated by quercetin in ARPE-19 cells. In conclusion, our present data suggests that HNE is highly toxic to serum-starved ARPE-19 cells but quercetin is able to reverse these adverse effects even when administered after an oxidative insult.
authors: Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O.B. 1627, FI-70211 Kuopio, Finland. Electronic address: maria.hytti@uef.fi.
authors: Maria
authors: M
authors: Hytti
authors: Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O.B. 1627, FI-70211 Kuopio, Finland. Electronic address: niina.e.laakso@uef.fi.
authors: Niina
authors: N
authors: Piippo
authors: Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, P.O.B. 1627, FI-70211 Kuopio, Finland; Department of Neurology, Kuopio University Hospital, P.O.B. 100, FI-70029 KYS, Finland. Electronic address: antero.salminen@uef.fi.
authors: Antero
authors: A
authors: Salminen
authors: School of Pharmacy, Faculty of Health Science, University of Eastern Finland, P.O.B. 1627, FI-70211, Finland. Electronic address: paavo.honkakoski@uef.fi.
authors: Paavo
authors: P
authors: Honkakoski
authors: 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. Electronic address: kai.kaarniranta@uef.fi.
authors: Kai
authors: K
authors: Kaarniranta
authors: 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. Electronic address: anu.kauppinen@uef.fi.
authors: Anu
authors: A
authors: Kauppinen
mesh_terms: D000447:Aldehydes / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011794:Quercetin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000447:Aldehydes; D000975:Antioxidants; D018925:Chemokines; D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D011794:Quercetin; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C027576:4-hydroxy-2-nonenal
keywords: 4-Hydroxynonenal; Inflammation; Oxidative stress; Quercetin; Retinal pigment epithelium