Species differences in serum paraoxonase correlate with sensitivity to paraoxon toxicity.
Costa LG; Richter RJ; Murphy SD; Omenn GS; Motulsky AG; Furlong CE
Toxicology of Pesticides: Experimental, Clinical and Regulatory Aspects, NATO ASI Series 1987;():263-266
Studies were conducted to determine whether the rabbit and the rat were affected differently by paraoxon (311455) because of their differences in serum paraoxonase activity. Following several trials, it was determined that the minimal effective doses of paraoxon were 0.5mg/kg in the rat and 2.0mg/kg in the rabbit. Doses of paraoxon of 0.5mg/kg in the rat and 2.0mg/kg in the rabbit caused similar degrees of cholinesterase inhibition. Percent inhibition was 66% and 79% in the diaphragm, 83 and 96% in plasma, and 60 and 76% in the hippocampus in rats and rabbits, respectively. An examination was also undertaken of the muscarinic receptor function in rat and rabbit brain by measuring the accumulation of inositol phosphates in cerebral cortex slices following stimulation by the cholinergic agonist carbachol. No difference was noted in the ability of carbachol to stimulate phosphoinositide hydrolysis in the two species. The findings indicated that a seven fold difference in serum paraoxonase resulted in a four fold difference in sensitivity to paraoxon toxicity. The difference in sensitivity was not due to the intrinsic characteristics of the primary target or a secondary target. It appeared that paraoxonase levels were similar between rat and rabbit in liver, kidney, spleen, and brain, thus leaving serum paraoxonase as the only significant difference between the two species. The authors suggest that surveys of farm workers for paraoxonase levels and symptoms of organophosphate toxicity are highly warranted.
NIOSH-Publication; NIOSH-Grant; Grants-other; Agricultural-workers; Enzyme-activity; Pesticides; Agricultural-chemicals; Laboratory-animals; Comparative-toxicology; Organo-phosphorus-pesticides;
Environmental Health University of Washington Dept of Environ Hlth, SC-34 Seattle, WA 98195
Other Occupational Concerns; Grants-other
Toxicology of Pesticides: Experimental, Clinical and Regulatory Aspects, NATO ASI Series
University of Washington, Seattle, Washington