title: Fisetin prevents fluoride- and dexamethasone-induced oxidative damage in osteoblast and hippocampal cells.
abstract: Fluoride intoxication and dexamethasone treatment produce deleterious effects in bone and brain. The aim of this study was to evaluate the effect of fluoride (F) and dexamethasone (Dex) co-exposure on oxidative stress and apoptosis in osteoblast-like MC3T3-E1 and hippocampal HT22 cell lines. Co-exposure to F and Dex resulted in a concentration-dependent decrease in cell viability, induction of apoptosis and increased generation of reactive oxygen species (ROS) and nitric oxide (NO) following 72 h of incubation. Fluoride-induced apoptosis in MC3T3-E1 and HT22 cells was attenuated by catalase and L-NNMA, indicating a role for H2O2 and NO as mediators of cytotoxicity. Dexamethasone-induced apoptosis was associated with H2O2 generation in both cell lines and it was attenuated during co-incubation with catalase. These data indicate that co-exposure to F and Dex amplifies their respective cytotoxicity in H2O2- and NO-dependent manner. As flavonoid fisetin prevented F- and Dex-induced cytotoxicity the potential role of this product in pharmacology and diet may be considered.
authors.affiliation: Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland. iinkiel@gumed.edu.pl
authors.forename: Iwona
authors.initials: I
authors.lastname: Inkielewicz-Stepniak
authors.forename: Marek W
authors.initials: MW
authors.lastname: Radomski
authors.forename: Michal
authors.initials: M
authors.lastname: Wozniak
mesh_terms: D000818:Animals; D002460:Cell Line; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D005434:Flow Cytometry; D005459:Fluorides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D005419:Flavonoids; D044948:Flavonols; D003907:Dexamethasone; C017875:fisetin; D005459:Fluorides