Apoptosis, Shape Change and Reactive Oxygen Species Generation in Human Neutrophils Exposed to Olanzapine, an Atypical Antipsychotic Drug

the effects of olanzapine (olz) on the viability and functioning of human polymorphonuclear cells (pmns) are clearly opposite to those previously reported for clozapine (clz). in fact, after 4- or 24-h-treatment with 20-50 μm olz, a significant inhibition of the respiratory burst in pmns activated with opsonized zimosan or phorbol myristate acetate (pma) was observed, whereas the burst provoked by formyl-methionyl-leucyl-phenylalanine (fmlp) was only inhibited at 50 μm olz. under the same conditions, spontaneous apoptosis was accelerated at 20-50 μm olz, while the exogenous addition of h2o2 resulted in the pmn apoptosis being dose-dependently inhibited by olz in the entire range of concentrations. however, when h2o2 was intracellularly generated by treatment with pma, the induced apoptosis was only decreased at 2 μm olz. absorbance scans revealed that olz is able to react with equimolar quantities of either h2o2 or hocl. these results suggest that olz inhibits both ros-induced pmn apoptosis and respiratory burst due to extracellular scavenging of released ros.