Na+/K+-ATPase in rat brain and erythrocytes as a possible target and marker, respectively, for neurotoxicity: studies with chlordecone, organotins and mercury compounds.
Toxicol Lett 1990 Apr; 51(2):175-188
The general aim of this study was to determine whether parameters of neurotransmission present in blood cells could serve as peripheral indicators of neurotoxicity, specifically the enzyme Na+/K+-ATPase which is important in regulating membrane function and neurotransmission. To validate the use of measurements of Na+/K+- ATPase in erythrocytes as a marker for the same enzyme in brain, the organochlorine pesticide chlordecone (143500), the organotins triethyltin (997502) and tributyltin (688733), mercuric-chloride (7487947) and methyl-mercury were chosen as chemical probes. Male Sprague-Dawley-rats were used in this study. All the compounds tested were shown to be potent in-vitro inhibitors of brain and erythrocyte Na+/K+-ATPase, yet administration of these compounds in- vivo at high doses produced symptoms of neurotoxicity without a corresponding inhibition of Na+/K+-ATPase. The reasons for the discrepancy between in-vitro inhibition and lack of detectable in- vivo inhibition is not always clear. In the case of triethyltin, mercuric-chloride, and methylmercury, the metal levels present in the brain following administration of neurotoxic doses were not high enough to inhibit Na+/K+-ATPase. No consistent patterns of parallel effects of enzyme activity in brain and erythrocytes was observed following in-vivo administration of various neurotoxic compounds. However, the recent finding of decreased erythrocyte Na+/K+-ATPase activities in workers chronically exposed to mercury (7439976) still suggests that chronic studies may be needed to infer or rule out conclusively a role for erythrocyte Na+/K+-ATPase as a useful peripheral marker for exposure to certain neurotoxicants.
NIOSH-Publication; NIOSH-Grant; Blood-analysis; Cell-function; Biological-monitoring; Mercury-poisoning; Pesticides; Laboratory-animals; Chlorinated-hydrocarbons; Organo-mercury-compounds; Neurotoxic-effects;
Author Keywords: Na+/K+ -ATPase; Peripheral marker; Chlordecone; Organotins; Mercury; Neurotoxicity
Environmental Health University of Washington Dept of Environ Hlth, SC-34 Seattle, WA 98195
143-50-0; 997-50-2; 688-73-3; 7487-94-7; 7439-97-6
Neurotoxic Disorders; Neurotoxic-effects
University of Washington, Seattle, Washington