Caenorhabditis elegans chronically exposed to a Mn/Zn ethylene-bis-dithiocarbamate fungicide show mitochondrial Complex I inhibition and increased reactive oxygen species

• Published in: Neurotoxicology (Park Forest South) 2016-09, Vol.56, p.170-179
• Main Authors: Bailey, Denise C., Todt, Callie E., Orfield, Sarah E., Denney, Rachel D., Snapp, Isaac B., Negga, Rekek, Montgomery, Kara M., Bailey, Andrew C., Pressley, Aireal S., Traynor, Wendy L., Fitsanakis, Vanessa A.
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Animals; C. elegans; Caenorhabditis elegans; Caenorhabditis elegans - drug effects; Complex I; Electron Transport Complex I - metabolism; Electron Transport Complex II - metabolism; Fungicides, Industrial - toxicity; Glutathione Transferase - metabolism; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Hydrogen peroxide; Hydrogen Peroxide - metabolism; Hydroxyl Radical - metabolism; Malonates - toxicity; Mancozeb; Membrane Potential, Mitochondrial - drug effects; Mitochondria - drug effects; Mitochondrial inhibition; Oxygen Consumption - drug effects; Reactive oxygen species; Reactive Oxygen Species - metabolism; Up-Regulation - drug effects
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2016.07.011

•C. elegans treated with the fungicide manzate show reduced mitochondrial respiration.•The decreased respiration can be attributed to Complex I inhibition.•Increased hydrogen peroxide, but not other reactive oxygen species, was detected.•Increased glutathione-S-transferase levels were also observed.•Mitochondrial inhibition and oxidative stress may be mechanisms of manzate toxicity. Reports have linked human exposure to Mn/Zn ethylene-bis-dithiocarbamate (Mn/Zn-EBDC) fungicides with multiple pathologies, from dermatitis to central nervous system dysfunction. Although members of this family of agrochemicals have been available for over 50 years, their mechanism of toxicity in humans is still unclear. Since mitochondrial inhibition and oxidative stress are implicated in a wide variety of diseases, we hypothesized that Caenorhabditis elegans (C. elegans) exposed to a commercially-available formulation of an Mn/Zn-EBDC-containing fungicide (Manzate; MZ) would also show these endpoints. Thus, worms were treated chronically (24h) with various MZ concentrations and assayed for reduced mitochondrial function and increased levels of reactive oxygen species (ROS). Oxygen consumption studies suggested Complex I inhibition in all treatment groups compared to controls (**p