Abstract

VARGAS, F; CHAVEZ, V  and  PEREZ, K. Apoptosis, Shape Change and Reactive Oxygen Species Generation in Human Neutrophils Exposed to Olanzapine, an Atypical Antipsychotic Drug. Rev. colomb. cienc. quim. farm. [online]. 2009, vol.38, n.1, pp.5-18. ISSN 0034-7418.

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.

Keywords : Olanzapine; neutrophils; apoptosis; respiratory burst; shape change; oxidative stress.

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