Dose-dependent inhibition of phospholipase A sub(2) by paraoxon in vitro: Preliminary results

• Published in: Journal of applied toxicology Vol. 17; no. 6; pp. 421 - 423
• Main Authors: Petroianu, G, Helfrich, U, Schmitt, A, Bergler, W, Ruefer, R
• Format: Journal Article
• Language: English
• Published: 01.12.1997
• ISSN: 0260-437X

To establish the dose dependency of phospholipase A sub(2) (PLA sub(2)) inhibition by the organophosphorus compound (OPC) paraoxon (POX), human platelet membranes were incubated after Ca super(2+) removal (to inactivate the PLA sub(2)) with 0.3, 1 and 3 mu g ml super(-1) POX for 5, 30 and 60 min each. The PLA sub(2) activity (pmol mg super(-1) protein min super(-1)) was measured after subsequent enzyme reactivation. The PLA sub(2) activity in native platelets was considered to be 100%; all other measured values are expressed as a percentage thereof. Data were analysed with the Mann-Whitney Wilcoxon rank order test and ANOVA. Statistical significance was assumed for P less than or equal to 0.01. Paraoxon inhibited in a dose-dependent manner the PLA sub(2) activity. Different incubation times of the inactive PLA sub(2) with POX did not have any additional effect on the activity reduction after activation. At the tested POX concentrations the PLA sub(2) activity was 42 plus or minus 5.4%, 29 plus or minus 3.4% and 15 plus or minus 6.6%, respectively. The corresponding butyrylcholine esterase (BChE) activities were <<1% of the baseline activity. Phospholipase A sub(2) is less sensitive to POX inhibition than BChE and, at clinically achievable POX concentrations, shows a clear dose dependency. Further work is needed to elucidate the exact mechanism and time dependency of the phenomenon.