Inactivation of Malaoxon by Mouse Liver 1

Abstract

Summary

Comparison of the manometric and anti-CHE methods for measuring malaoxon detoxification in vitro demonstrated that carboxylesterase hydrolysis of malaoxon accounted for only about 1/2 of the total malaoxon detoxification detected by the anti-CHE method. Evidence was obtained which showed that there was a rapid, temperature-independent loss of anti-CHE activity of malaoxon in the presence of liver which suggested that the discrepancy was due to non-catalytic binding of malaoxon to tissue constituents. Malaoxon binding was inhibited by malathion-potentiating doses of other organ-ophosphates which alsc inhibited carboxylesterase activity, in vivo. A close dose—effect correlation was observed between carboxylesterase inhibition and inhibition of malaoxon binding. This suggests that carboxylesterase enzymes may act as noncritical binding sites for malaoxon inactivation. Malaoxon binding, as well as catalytic hydrolysis, may play a role in malaoxon detoxification and inhibiton of binding may contribute to potentiation of malaoxon by compounds which compete for binding sites.

The authors acknowledge the valuable technical assistance provided by Mrs. Janet E. Callaghan.