Oxygen and Arsenite Synergize Phosphine Toxicity by Distinct Mechanisms
| Autor: | Paul R. Ebert, Saad M. Alzahrani |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Hot Temperature Arsenites Phosphines Drug Resistance chemistry.chemical_element Toxicology Oxygen Microbiology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Caenorhabditis elegans Dihydrolipoamide Dehydrogenase Arsenite Hyperoxia Dihydrolipoamide dehydrogenase Drug Synergism Models Theoretical 030104 developmental biology chemistry Mechanism of action Mutation Toxicity Limiting oxygen concentration Pest Control medicine.symptom 030217 neurology & neurosurgery Phosphine |
| Zdroj: | Toxicological Sciences. 167:419-425 |
| ISSN: | 1096-0929 1096-6080 |
| DOI: | 10.1093/toxsci/kfy248 |
| Popis: | Phosphine is the only fumigant approved globally for general use to control insect pests in stored grain. Due to the emergence of resistance among insect pests and the lack of suitable alternative fumigants, we are investigating ways to synergistically enhance phosphine toxicity, by studying the mechanism of action of known synergists, such as oxygen, temperature, and arsenite. Under normoxia, exposure of the model organism Caenorhabditis elegans for 24 h at 20°C to 70 ppm phosphine resulted in 10% mortality, but nearly 100% mortality if the oxygen concentration was increased to 80%. In wild-type C. elegans, toxicity of phosphine was negatively affected by a decrease in temperature to 15°C and positively affected by an increase in temperature to 25°C. The dld-1(wr4) strain of C. elegans is resistant to phosphine due to a mutation in the dihydrolipoamide dehydrogenase gene. It also exhibits increased mortality that is dependent on hyperoxia, when exposed to 70 ppm phosphine at 20°C. As with the wild-type strain, mortality decreased when exposure was carried out at 15°C. At 25°C, however, the strain was completely resistant to the phosphine exposure at all oxygen concentrations. Arsenite is also a synergist of phosphine toxicity, but only in the dld-1(wr4)-mutant strain. Thus, exposure to 4 mM arsenite resulted in 50% mortality, which increased to 89% mortality when 70 ppm phosphine and 4 mM arsenite were combined. In stark contrast, 70 ppm phosphine rendered 4 mM arsenite nontoxic to wild-type C. elegans. These results reveal two synergists with distinct modes of action, one of which targets individuals that carry a phosphine resistance allele in the dihydrolipoamide dehydrogenase gene. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|