title: Zearalenone induced toxicity in SHSY-5Y cells: The role of oxidative stress evidenced by N-acetyl cysteine.
abstract: Zearalenone (ZEN) is a mycotoxin from Fusarium species commonly found in many food commodities and are known to cause reproductive disorders, genotoxic and immunosuppressive effects. Although many studies have demonstrated the cytotoxic effects of ZEN, the mechanisms by which ZEN mediates its cytotoxic effects appear to differ according to cell type and route of exposure. Meantime, the available information on the neurotoxic effects of ZEN is very much limited. In the present study we evaluated the role of oxidative stress in ZEN mediated neurotoxicity in SH-SY5Y cells and investigated the possible underlying mechanism. ZEN induced ROS formation and elevated levels of MDA, loss of mitochondrial membrane potential (MMP) and increase in DNA damage in a dose dependent manner as assessed by COMET assay and agarose gel electrophoresis. However, there was no DNA damage by plasmid breakage assay at 6, 12 and 24h time points. DAPI staining showed apoptotic nuclei at 12 and 24h. Further, ZEN treated SH-SY5Y cells showed a marked suppressive effect on the neuronal gene expression. Use of an antioxidant N-acetylcysteine (NAC) reversed the toxin-induced generation of ROS and also attenuated loss of MMP. Collectively, these results suggest that ROS is the main upstream signal leading to increased ZEN mediated neurotoxicity in SH-SY5Y cells.
authors.affiliation: DRDO-BU Centre for Life Sciences, Coimbatore, Tamilnadu 641046, India.
authors.forename: M
authors.initials: M
authors.lastname: Venkataramana
authors.affiliation: DOS in Biotechnology, University of Mysore, Mysore 570006, Karnataka, India. Electronic address: moonnayak@gmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Chandra Nayaka
authors.affiliation: Defence Food Research Laboratory, Siddhartha Nagar, Mysore, Karnataka, India.
authors.forename: T
authors.initials: T
authors.lastname: Anand
authors.affiliation: Department of Microbiology and Immunology, The University of Maryland, School of Medicine, Baltimore, MD 21201, United States.
authors.forename: Rajaiah
authors.initials: R
authors.lastname: Rajesh
authors.affiliation: DOS in Biotechnology, University of Mysore, Mysore 570006, Karnataka, India.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Aiyaz
authors.affiliation: DOS in Biotechnology, University of Mysore, Mysore 570006, Karnataka, India.
authors.forename: S T
authors.initials: ST
authors.lastname: Divakara
authors.affiliation: Defence Food Research Laboratory, Siddhartha Nagar, Mysore, Karnataka, India.
authors.forename: H S
authors.initials: HS
authors.lastname: Murali
authors.affiliation: DOS in Biotechnology, University of Mysore, Mysore 570006, Karnataka, India.
authors.forename: H S
authors.initials: HS
authors.lastname: Prakash
authors.affiliation: DRDO-BU Centre for Life Sciences, Coimbatore, Tamilnadu 641046, India.
authors.forename: P V
authors.initials: PV
authors.lastname: Lakshmana Rao
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015025:Zearalenone / Q000633:toxicity*
chemical_list: D017931:DNA Primers; D017382:Reactive Oxygen Species; D015025:Zearalenone; D000111:Acetylcysteine
keywords: Mycotoxin; NAC; Neurotoxicity; ROS; Zearalenone