Mitochondrial dysfunction from malathion and chlorpyrifos exposure is associated with degeneration of GABAergic neurons in Caenorhabditis elegans |
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| Institution: | 1. Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok Thailand;2. Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok Thailand;1. Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA 52242, United States;2. Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA 52242, United States;3. IIHR Hydroscience and Engineering, The University of Iowa, Iowa City, IA 52242, United States;4. Department of Civil and Environmental Engineering, The University of Iowa, Iowa City, IA 52242, United States;5. Center for Health Effects of Environmental Contamination, The University of Iowa, Iowa City, IA 52242;1. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Pennsylvania State University, College of Medicine, Hershey, PA, USA;2. Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA, USA;3. Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Irvine, CA, USA;4. Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA;5. Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO, USA;6. Department of Medicine, University of California, San Diego, La Jolla, CA, USA;7. Heart and Vascular Institute, Department of Medicine, Pennsylvania State University, College of Medicine, Hershey, PA, USA;1. Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-University, Im Neuenheimer Feld 329, 69120 Heidelberg, Germany;2. A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio 70211, Finland;3. Department of Environmental and Biological Sciences, University of Eastern Finland, Kuopio 70211, Finland;4. School of Pharmacy, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland;1. Department of Zoology, University of Calcutta, Kolkata 700019, India;2. Department of Zoology, University of North Bengal, Darjeeling 734013, India;3. Department of Physiology, Medical College and Hospital, Kolkata, India;4. Fisheries and Ecotoxicology Research Laboratory Vice Chancellor’s Research Group, Department of Zoology, The University of Burdwan, Purba bardhaman, Burdwan 713104, West Bengal, India;1. Department of Pharmacology, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey;2. Department of Medical Biology, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey;3. Department of Anatomy, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey;4. Department of Pathology, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey;1. Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, China;2. Faculty of Public Health, Pyongyang Medical University, Pyongyang, Democratic People''s Republic of Korea |
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| Abstract: | Toxicity resulting from off-target effects, beyond acetylcholine esterase inhibition, for the commonly used organophosphate (OP) insecticides chlorpyrifos (CPS) and malathion (MA) was investigated using Saccharomyces cerevisiae and Caenorhabditis elegans model systems. Mitochondrial damage and dysfunction were observed in yeast following exposure to CPS and MA, suggesting this organelle is a major target. In the C. elegans model, the mitochondrial unfolded protein response pathway showed the most robust induction from CPS and MA treatment among stress responses examined. GABAergic neurodegeneration was observed with CPS and MA exposure. Impaired movement observed in C. elegans exposed to CPS and MA may be the result of motor neuron damage. Our analysis suggests that stress from CPS and MA results in mitochondrial dysfunction, with GABAergic neurons sensitized to these effects. These findings may aid in the understanding of toxicity from CPS and MA from high concentration exposure leading to insecticide poisoning. |
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| Keywords: | Organophosphate insecticides Malathion Chlorpyrifos Neurodegeneration Mitochondria dysfunction |
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