title: Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin A.
abstract: Oxidative stress and DNA damage are the most studied mechanisms by which ochratoxin A (OTA) induces its toxic effects, which include nephrotoxicity, hepatotoxicity, immunotoxicity and genotoxicity. Zinc, which is an essential trace element, is considered a potential antioxidant. The aim of this paper was to investigate whether zinc supplement could inhibit OTA-induced oxidative damage and DNA damage in HepG2 cells and the mechanism of inhibition. The results indicated that that exposure of OTA decreased the intracellular zinc concentration; zinc supplement significantly reduced the OTA-induced production of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity but did not affect the OTA-induced decrease in the mitochondrial membrane potential (Δψm). Meanwhile, the addition of the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly aggravated the OTA-induced oxidative damage. This study also demonstrated that zinc helped to maintain the integrity of DNA through the reduction of OTA-induced DNA strand breaks, 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation and DNA hypomethylation. OTA increased the mRNA expression of metallothionein1-A (MT1A), metallothionein2-A (MT2A) and Cu/Zn superoxide dismutase (SOD1). Zinc supplement further enhanced the mRNA expression of MT1A and MT2A, but it had no effect on the mRNA expression of SOD1 and catalase (CAT). Zinc was for the first time proven to reduce the cytotoxicity of OTA through inhibiting the oxidative damage and DNA damage, and regulating the expression of zinc-associated genes. Thus, the addition of zinc can potentially be used to reduce the OTA toxicity of contaminated feeds.
authors: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China.
authors: Juanjuan
authors: J
authors: Zheng
authors: Yu
authors: Y
authors: Zhang
authors: Wentao
authors: W
authors: Xu
authors: YunBo
authors: Y
authors: Luo
authors: Junran
authors: J
authors: Hao
authors: Xiao Li
authors: XL
authors: Shen
authors: Xuan
authors: X
authors: Yang
authors: Xiaohong
authors: X
authors: Li
authors: Kunlun
authors: K
authors: Huang
mesh_terms: D002374:Catalase / Q000235:genetics; D019610:Cytoprotection; D004249:DNA Damage; D005021:Ethylamines / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008668:Metallothionein / Q000235:genetics; D009183:Mycotoxins / Q000633:toxicity*; D009793:Ochratoxins / Q000633:toxicity*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D015032:Zinc / Q000032:analysis / Q000494:pharmacology*
chemical_list: D005021:Ethylamines; C491053:MT2A protein, human; D009183:Mycotoxins; C511824:N,N,N',N'-tetrakis(2-pyridylmethyl)ethane-1,2-diamine; D009793:Ochratoxins; D011725:Pyridines; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C025589:ochratoxin A; D008668:Metallothionein; D002374:Catalase; D013482:Superoxide Dismutase; D015032:Zinc