Chlorate Poisoning: Mechanism of Toxicity
The clinical course of chlorate poisoning is characterized by the formation of methaemoglobin (Hbi) followed by haemolysis and intravascular coagulation. As methylene blue was clinically not effective in the treatment of this intoxication, the effect of chlorate on human erythrocytes in vitro, was studied. Incubation with chlorate caused a rapid glutathione oxidation and Hbi formation with a lag phase that was concentration-dependent. Enzyme activities decreased in the following order: ATPase, glucose-6-phosphate dehydrogenase, hexokinase. Glutathione reductase was not altered. Membrane alterations were suspected, since the erythrocytes showed an increased resistance to hypotonic haemolysis and a decrease of the intracellular potassium concentration during the incubation. These alterations could be demonstrated by filtration through polycarbonate membranes (Steffen and Singleman 1983). Filtration times increased from 2.5 to 100 sec after 120 min incubation with 30 mM chlorate. Polyacrylamide electrophoresis revealed a cross-linking of membrane proteins. Hbi formation by chlorate was essentially irreversible. Only in the early phase was an enzymatic reduction catalyzed by methylene blue possible. Later on, chemical reduction to haemoglobin was impossible, too. When sodium nitrite was used as an oxidant, enzymatic reduction to haemoglobin was possible during the complete experimental period of 3 hr.
Based on the clinical and experimental observations, an immediate exchange transfusion in all cases of chlorate poisoning is suggested.