Bipyridylium herbicide toxicity in vitro: comparative study of the cytotoxicity of paraquat and diquat toward the pulmonary alveolar macrophage.
In vitro exposure of adult rat alveolar macrophages to either paraquat or diquat resulted in concentration dependent cytotoxicity (cell death). The herbicide paraquat, however was statistically significantly more potent toward these cells than was diquat. The LC50 value for paraquat (8-h exposure, 37 degrees C) was determined to be 0.94 mM [95% confidence interval (C.I.) 0.79-1.12 mM], whereas the corresponding LC50 value for diquat was 1.97 mM (C.I. 1.58-2.51 mM). Interestingly, diquat was shown to enter these cells to a much greater extent than was paraquat. The latter data, while seemingly contradictory to the above findings, is consistent with other reported findings in this study that show that cell respiration, as measured by loss of oxygen consumption, was more sensitive to diquat than it was to paraquat. Also, only paraquat cytotoxicity was found to be dependent on oxygen tension and could be altered by the presence of antioxidant enzymes in the culture medium. Both compounds, however, were found to be equipotent toward purified mitochondria. Both paraquat and diquat were able to uncouple oxidative phosphorylation and induce active oxygen species (superoxide anions and hydrogen peroxide) from this organelle. It is concluded that free-radical pathology is the most likely mechanism of action by which paraquat is cytotoxic toward these cells, but that diquat poisoning probably originates from some other mode of action.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004178:Diquat / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D010101:Oxygen Consumption / Q000187:drug effects; D010269:Paraquat / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D013481:Superoxides / Q000096:biosynthesis
D011506:Proteins; D013481:Superoxides; D004178:Diquat; D006861:Hydrogen Peroxide; D010269:Paraquat