2. Academic Validation
  3. The Pesticide Metabolites Paraoxon and Malaoxon Induce Cellular Death by Different Mechanisms in Cultured Human Pulmonary Cells

The Pesticide Metabolites Paraoxon and Malaoxon Induce Cellular Death by Different Mechanisms in Cultured Human Pulmonary Cells

  • Int J Toxicol. 2015 Sep-Oct;34(5):433-41. doi: 10.1177/1091581815593933.
Daniel J Angelini 1,  Robert A Moyer 2,  Stephanie Cole 3,  Kristen L Willis 4,  Jonathan Oyler 5,  Russell M Dorsey 6,  Harry Salem 7
Affiliations

Affiliations

  • 1 National Research Council, Research Associates Program, Washington DC, USA Excet Inc, Springfield, VA, USA daniel.j.angelini2.ctr@mail.mil.
  • 2 Chemical & Biological Technologies Department, Defense Threat Reduction Agency, Fort Belvoir, VA, USA Battelle Memorial Institute, Columbus, OH, USA.
  • 3 National Research Council, Research Associates Program, Washington DC, USA Excet Inc, Springfield, VA, USA Chemical & Biological Technologies Department, Defense Threat Reduction Agency, Fort Belvoir, VA, USA.
  • 4 National Research Council, Research Associates Program, Washington DC, USA Chemical & Biological Technologies Department, Defense Threat Reduction Agency, Fort Belvoir, VA, USA.
  • 5 U.S. Army Medical Command, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Aberdeen, MD, USA.
  • 6 U.S. Army Research Development and Engineering Command, Edgewood Chemical Biological Center, Aberdeen Proving Ground, MD, USA.
  • 7 U.S. Army Research Development and Engineering Command, Edgewood Chemical Biological Center, Aberdeen Proving Ground, MD, USA Department of Homeland Security, Chemical Security Assessment Center, Aberdeen Proving Ground, MD, USA.
PMID: 26173615 DOI: 10.1177/1091581815593933
Abstract

Organophosphorus (OP) pesticides are known to induce pulmonary toxicity in both humans and experimental Animals. To elucidate the mechanism of OP-induced cytotoxicity, we examined the effects of parathion and malathion and their respective metabolites, paraoxon and malaoxon, on primary cultured human large and small airway cells. Exposure to paraoxon and malaoxon produced a dose-dependent increase in cytotoxicity following a 24-hour exposure, while treatment with parathion or malathion produced no effects at clinically relevant concentrations. Exposure to paraoxon-induced Caspase activation, but malaoxon failed to induce this response. Since caspases have a major role in the regulation of Apoptosis and cell death, we evaluated OP-induced cell death in the presence of a Caspase Inhibitor. Pharmacological Caspase inhibition protected against paraoxon-induced cell death but not malaoxon-induced cell death. These data suggest that Caspase activation is a key signaling element in paraoxon-induced cell death, but not malaoxon-induced cellular death in the pulmonary epithelium.

Keywords

apoptosis; caspase; malaoxon; necrosis; organophosphates; paraoxon; pulmonary toxicity.

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