title: Resveratrol induces pro-oxidant effects and time-dependent resistance to cytotoxicity in activated hepatic stellate cells.
abstract: Resveratrol (RSV) is known for its antioxidant properties; however, this compound has been proposed to have cytotoxic and pro-oxidant effects depending on its concentration and time of exposure. We previously reported the cell cycle arrest effect of low doses of RSV in GRX cells, an activated hepatic stellate cell model. Here, we evaluated the effects of RSV treatment (0.1-50 μM) for 24 and 120 h on GRX viability and oxidative status. Only treatment with 50 μM of RSV reduced the amount of live cells. However, even low doses of RSV induced an increased reactive species production at both treatment times. While being diminished within 24 h, RSV induced an increase in the SOD activity in 120 h. The cellular damage was substantially increased at 24 h in the 50 μM RSV-treated group, as indicated by the high lipoperoxidation, which may be related to the significant cell death and low proliferation. Paradoxically, this cellular damage and lipoperoxidation were considerably reduced in this group after 120 h of treatment while the surviving cells proliferated. In conclusion, RSV induced a dose-dependent pro-oxidant effect in GRX cells. The highest RSV dose induced oxidative-related damage, drastically reducing cell viability; but this cytotoxicity seems to be attenuated during 120 h of treatment.
authors.affiliation: Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2600-Anexo I, Porto Alegre, RS, CEP 90035-003, Brazil, leo.meira@ufrgs.br.
authors.forename: Leo A Meira
authors.initials: LA
authors.lastname: Martins
authors.forename: Bárbara P
authors.initials: BP
authors.lastname: Coelho
authors.forename: Guilherme
authors.initials: G
authors.lastname: Behr
authors.forename: Letícia F
authors.initials: LF
authors.lastname: Pettenuzzo
authors.forename: Izabel C C
authors.initials: IC
authors.lastname: Souza
authors.forename: José Cláudio F
authors.initials: JC
authors.lastname: Moreira
authors.forename: Radovan
authors.initials: R
authors.lastname: Borojevic
authors.forename: Carmem
authors.initials: C
authors.lastname: Gottfried
authors.forename: Fátima Costa Rodrigues
authors.initials: FC
authors.lastname: Guma
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D017382:Reactive Oxygen Species; D013267:Stilbenes; D002374:Catalase; D013482:Superoxide Dismutase; D000077185:Resveratrol