Bipyridylium herbicide toxicity: effects of paraquat and diquat on isolated rat hepatocytes.
Paraquat (1,1'-dimethyl-4,4'-bipyridylium) and diquat (1,1'-ethylene-2,2'-bipyridylium) are the two most widely used bipyridylium herbicides today. Both compounds, however, have also been found to cause liver damage in animals and man. In this study, isolated rat hepatocytes were used to assess the cytotoxicity of these two compounds. Five indices of cell damage were used to quantitate cytotoxicity: dye (trypan blue) uptake, loss of cell respiration, the extracellular release of lysosomal enzymes, the formation of thiobarbiturate (TBA)-reacting substances, and the oxidation of cellular NADH and NADPH. Diquat was shown to be more toxic than paraquat toward these cells in the first three assay systems. The acute LC50 for diquat was determined to be 80 mM, whereas the acute LC50 for paraquat was estimated to be greater than 1 M. This difference in cell sensitivity could be explained, at least in part, by the observed differences in herbicide uptake rates for these two compounds. Diquat uptake was calculated to be 9.0 +/- 1.1 nmoles/hour/10(6) cells, whereas paraquat uptake was only 5.5 +/- 0.5 nmoles/hour/10(6) cells. The dose-response curves for enzyme release and loss of cell respiration superimposed the lethality curves for both compounds. An oxidative mechanism of cytotoxicity was suggested for diquat by: the establishment of both a concentration-dependent and a time-dependent increase in lipid peroxidation (formation of TBA-reacting substances); complete oxidation of both NADPH and NADH at herbicide levels less than the LC50; and the finding that diquat stimulated glucose oxidation at subtoxic doses.[1]References
- Bipyridylium herbicide toxicity: effects of paraquat and diquat on isolated rat hepatocytes. Suleiman, S.A., Stevens, J.B. J. Environ. Pathol. Toxicol. Oncol. (1987) [Pubmed]
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