In vivoadministration of acepromazine or promethazine to horse decreases the reactive oxygen species production response of subsequently isolated neutrophils to stimulation with phorbol myristate acetate

Abstract

The previous experiments have shown that some phenothiazines have antioxidant and anti-inflammatory properties in vitro. In this study the inhibition of the production of reactive oxygen species (ROS) by neutrophils was studied in two groups of horses, which received a dose of 0.1 mg/kg of either acepromazine or promethazine intravenously. Blood samples were collected before (T0) and 0.5, 1, 3 and 5 h after drug administration. The chemiluminescence (CML) response of neutrophils was measured ex vivo in the presence of luminol for a period of 10 min and the maximum CML value (peak value) recorded. There was a significant inhibition of the ROS production in the acepromazine treated group (49% inhibition) at 5 h after administration and in the promethazine group (24% inhibition) at 3 h after administration (P < 0.05 vs. T0). These findings are of therapeutic relevance in the use of phenothiazines in equine patients with inflammatory diseases where neutrophil activation and ROS production are implicated.

Comparison of the Sedative and Hemodynamic Effects of Acepromazine and Promethazine in the Standing Horse

“…ACP was used in this study at 0.1 mg/kg, the highest manufacturer-recommended dose, as this is the dose at which anti-inflammatory effects have been demonstrated [15,17]. Three doses of PTZ were used to enrich the results and were based on the results from preliminary studies.…”

“…Additionally, it has been shown in vitro that ACP reduces the tumor necrosis factor-a production of monocytes [13], inhibits the differentiation of monocytes into macrophages [14], and, decreases the production of reactive oxygen species or its by-products [15][16][17][18]; PTZ also can produce the latter effect.…”

Loss-of-function of neuroplasticity-related genes confers risk for human neurodevelopmental disorders

“…In contrast, antipsychotics appear to induce an immature granulocytic phenotype [45]. This has generally been considered a side-effect (and is separate from potentially fatal agranulocytosis, as induced by clozapine [46]), but neutrophils in drug-free individuals with schizophrenia generate elevated reactive oxygen species (ROS) [47,48] and ROS levels can be normalized by antipsychotics [49,50]. It should be noted, however, that one study found antipsychotics did not decrease ROS in patients with schizophrenia [51].…”

Modulating effects of acepromazine on the reactive oxygen species production by stimulated equine neutrophils

“…In previous studies, our group has shown that ACP induces interesting modulator effects on neutrophil activation. These effects are mainly studied on the capacity of ACP to neutralize ROS produced by stimulated equine neutrophils by using luminol‐enhanced chemiluminescence (Serteyn et al 1999; Péters et al. 2009).…”

“…1999). Interestingly, Péters et al. (2009) showed that after an in vivo administration of promethazine or ACP to horses, the antioxidant effect of these drugs still persist in isolated and washed neutrophils.…”