The Pesticide Metabolites Paraoxon and Malaoxon Induce Cellular Death by Different Mechanisms in Cultured Human Pulmonary Cells
| Autor: | Kristen L. Willis, Stephanie D. Cole, Robert A. Moyer, Harry Salem, Russell M. Dorsey, Daniel J. Angelini, Jonathan Oyler |
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| Rok vydání: | 2015 |
| Předmět: |
Insecticides
Programmed cell death Necrosis Cell Survival Respiratory System Pharmacology Toxicology Paraoxon Amino Acid Chloromethyl Ketones chemistry.chemical_compound Malaoxon medicine Humans Cytotoxicity Cells Cultured Caspase Cell Death Parathion biology Epithelial Cells Caspase Inhibitors chemistry Apoptosis Caspases Malathion biology.protein Cholinesterase Inhibitors medicine.symptom medicine.drug |
| Zdroj: | International Journal of Toxicology. 34:433-441 |
| ISSN: | 1092-874X 1091-5818 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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