Thiram-induced disturbance of microsomal phospholipid bioformation and phospholipid fatty acid pattern

In rats, a single oral dose of 30 mg or 1 g thiram per kilogram produced a significant prolongation of the hexobarbital sleeping time or zoxazolamine paralysis time, respectively, a depression of hepatic microsomal O-demethylation of p-nitroanisole to p-nitrophenol, and a decrease in the microsomal cytochrome P-450 content. In addition, incorporation of 14C activity from glucose, glycerol, and palmitic acid into phospholipids (PLs) decreased in most of the components, showing a compensatory increase in only a few of them. Fatty acid (FA) concentrations in phosphatidylcholine (PC) or phosphatidylethanolamine (PE) molecules were increased or decreased from one FA class to the other. This alteration of the FA concentrations in PC and PE, respectively, was virtually exclusively in position 2 of the two PL molecules. The total content of saturated FAs in PC and PE was significantly decreased only after 1 g/kg thiram; this was associated with an increase in total unsaturated FAs. The multiple changes in the bioformation and composition of microsomal membrane PLs suggest a disturbance of the monooxygenase system. It is conceivable that there is an interrelationship between the observed impairment and the inhibitory effect of thiram on the microsomal monoxygenases (MMs).