title: Prevention of cytotoxicity of nickel by quercetin: the role of reactive oxygen species and histone acetylation.
abstract: Excessive exposure to nickel may cause health effects on the blood, lung, nose, kidney, reproductive system, skin and the unborn child. In the present study, we found that Ni²⁺ exposure led to a time- and dose-dependent proliferation arrest and death in human leukemia HL-60 cells. In the presence of 1 mM Ni²⁺, reactive oxygen species (ROS) generation (indicated by the level of malondialdehyde) increased to 323% and histone acetylation decreased to 32%. Interestingly, quercetin (QU) dose dependently prevented Ni²⁺-induced cell proliferation arrest and death from 0 to 80 μM but showed similar activity of scavenging ROS at the concentrations of 20, 40 and 80 µM. When the effect of QU on histone acetylation was studied, QU significantly prevented Ni²⁺-induced histone hypoacetylation at 40 or 80 µM. Moreover, increase in histone acetylation by trichostatin A could also significantly enhance the protection effect of QU at 10 or 20 µM but not at higher concentrations. Thus, our results further confirmed the critical role of ROS and histone hypoacetylation in the cytotoxicity of Ni²⁺ exposure and proved that QU is a potentially useful native dietary compound to efficiently prevent Ni²⁺-caused cytotoxicity through both diminishing ROS generation and increasing histone acetylation.
authors.affiliation: Department of Hematology, Changhai Hospital, The Second Military Medical University, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Jia
authors.initials: J
authors.lastname: Han
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wang
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000975:Antioxidants / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D009532:Nickel / Q000633:toxicity*; D011794:Quercetin / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D017382:Reactive Oxygen Species; C012589:trichostatin A; D009532:Nickel; D011794:Quercetin