Changes in the levels and forms of rat plasma cholinesterases during chronic diisopropylphosphorofluoridate intoxication.

The effect of chronic administration of diisopropylphosphorofluoridate (DFP) on the levels and forms of plasma cholinesterase (ChE), were studied in male Wistar albino rats sacrificed at different time intervals after various schedules of treatment. In particular the inhibition and recovery rate of the enzymatic activity was evaluated for butyrylcholinesterase (BuChE), determined using butyrylthiocholine (BuThCh) as substrate and for acetylcholinesterase (AChE), measured using acetylthiocholine (AcThCh) in the presence of iso-OMPA 0.1 mM. At 1 1/2 and 24 hr after the DFP treatments, BuChE was considerably more depressed than was the case for AChE. Moreover, the recovery of BuChE proceeded more slowly, its activity being restored only seven days after the last treatment, while the recovery of AChE was completed 72 hr after the end of the treatments. Plasma molecular forms were separated by polyacrylamide gel electrophoresis and were revealed by enzymatic reaction with BuThCh or AcThCh as substrates. By using selective inhibitors, five main molecular forms of BuChE and two of AChE were found to exist in control plasma samples. A differential inhibition and recovery rate was observed among these forms after DFP intoxication. At 1 1/2 hr after the treatments, the BuChE activity was too low to be detected on the gels, but 24 hr thereafter, the quantitative determination of the different forms, performed by scanning densitometry, showed a significant increase of the two faster migrating ones. At the following time intervals, the electrophoretic pattern returned progressively towards normality. The faster migrating forms are therefore probably the first synthesized in the process of recovery of BuChE activity.(ABSTRACT TRUNCATED AT 250 WORDS)