title: Urolithins display both antioxidant and pro-oxidant activities depending on assay system and conditions.
abstract: The biological effects of polyphenolic ellagitannins are mediated by their intestinal metabolites, urolithins. This study investigated redox properties of urolithins A and B using ORAC assay, three cell-based assays, copper-initiated pro-oxidant activity (CIPA) assay, and cyclic voltammetry. Urolithins were strong antioxidants in the ORAC assay, but mostly pro-oxidants in cell-based assays, although urolithin A was an antioxidant in cell culture medium. Parent compound ellagic acid was a strong extracellular antioxidant, but showed no response in the intracellular assay. The CIPA assay confirmed the pro-oxidant activity of ellagitannin metabolites. In the cell proliferation assay, urolithins but not ellagic acid decreased growth and metabolism of HepG2 liver cells. In cyclic voltammetry, the oxidation of urolithin A was partly reversible, but that of urolithin B was irreversible. These results illustrate how strongly measured redox properties depend on the employed assay system and conditions and emphasize the importance of studying pro-oxidant and antioxidant activities in parallel.
authors.affiliation: CEMIS-Oulu, Kajaani University Consortium, University of Oulu , Sotkamo, Finland.
authors.forename: Tuija
authors.initials: T
authors.lastname: Kallio
authors.forename: Johanna
authors.initials: J
authors.lastname: Kallio
authors.forename: Mari
authors.initials: M
authors.lastname: Jaakkola
authors.forename: Marianne
authors.initials: M
authors.lastname: Mäki
authors.forename: Pekka
authors.initials: P
authors.lastname: Kilpeläinen
authors.forename: Vesa
authors.initials: V
authors.lastname: Virtanen
mesh_terms: D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology; D001681:Biological Assay; D049109:Cell Proliferation / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D016877:Oxidants / Q000737:chemistry* / Q000494:pharmacology; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D003374:Coumarins; D016877:Oxidants; D017382:Reactive Oxygen Species; C026423:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one