title: Dominant roles of Fenton reaction in sodium nitroprusside-induced chondrocyte apoptosis.
abstract: Sodium nitroprusside (SNP) has been widely used as an exogenous nitric oxide (NO) donor to explore the molecular mechanism of NO-mediated chondrocyte apoptosis during the latest two decades. We have recently found that NO-independent ROS play a key role in SNP-induced apoptosis in rabbit chondrocytes. This study aims to investigate what kind of ROS and how the reliable ROS mediators mediate the SNP-induced apoptosis. Data shows that SNP and NO-exhausted SNP (SNPex) induced ROS production or cytotoxicity to identically degree. SNP induced a marked increase in iron ions, superoxide anion (O2(•-)), hydrogen peroxide (H2O2) and hydroxyl radical ((•)OH) level. H2O2 scavenger (CAT) and (•)OH scavenger (DMSO) significantly inhibited SNP-induced chondrocyte apoptosis. Iron ions chelator (DFO) entirely prevented SNP-induced chondrocyte apoptosis. In contrast, O2(•-) scavenger (SOD) and glutathione depletion agent (BSO) promoted SNP-induced cytotoxicity. K3[Fe(CN)6] exhibited no cytotoxicity, and H2O2 alone up to 250µM or iron ions alone up to 90µM is non-cytotoxic to chondrocytes. Combination of 25µM FeSO4 and 100µM H2O2 in the presence of BSO induced chondrocyte death similar to SNP treatment. Fetal bovine serum (FBS) enhanced iron ions release from SNP and the cytotoxicity of SNP. Our data shows that the extracellular Fenton reaction between iron ions released from SNP and H2O2 induced by SNP plays a key role in SNP-induced chondrocyte apoptosis. Overall, our results indicate that the potential of SNP to increase iron ions and ROS should be especially considered for some biological functions and, possibly, also for clinical applications of this drug.
authors.affiliation: Department of Pain Management, the First Affiliated Hospital of Jinan University, Guangzhou, China.
authors.forename: Ying-Yao
authors.initials: YY
authors.lastname: Quan
authors.affiliation: MOE Key Laboratory of Laser Life Science & College of Life Science, South China Normal University, Guangzhou, China.
authors.forename: Gui-Qi
authors.initials: GQ
authors.lastname: Qin
authors.affiliation: Department of Pain Management, the First Affiliated Hospital of Jinan University, Guangzhou, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Pain Management, the First Affiliated Hospital of Jinan University, Guangzhou, China.
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Department of Pain Management, the First Affiliated Hospital of Jinan University, Guangzhou, China. Electronic address: txp2938@jnu.edu.cn.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Wang
authors.affiliation: MOE Key Laboratory of Laser Life Science & College of Life Science, South China Normal University, Guangzhou, China. Electronic address: chentsh@scnu.edu.cn.
authors.forename: Tong-Sheng
authors.initials: TS
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D017665:Hydroxyl Radical / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000378:metabolism; D009599:Nitroprusside / Q000378:metabolism*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: C045076:Fenton's reagent; D020030:Nitric Oxide Donors; D017382:Reactive Oxygen Species; D013481:Superoxides; D009599:Nitroprusside; D009569:Nitric Oxide; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D007501:Iron; D005978:Glutathione
keywords: Apoptosis; Chondrocyte; Fenton reaction; Iron ions; NO-independent; Sodium nitroprusside