(+)-Pentazocine reduces oxidative stress and apoptosis in microglia following hypoxia/reoxygenation injury

BackgroundSigma-1 receptors (σ1R) are highly expressed in neurons as well as microglia and have been shown to modulate the inflammatory response in the central nervous system and thus may serve as a possible target for neuroprotective strategies. The aim of the present study was to test the effect of (+)-pentazocine, a putative σ 1R agonist, in an in vitro model of microglia activation.MethodsMicroglia (BV2 cells) was exposed (3 hours) to 1% oxygen and reoxygenation was allowed for 24 hours. Cells were treated with different concentrations (1, 10, 25 and 50 μM) of (+)-pentazocine in the presence or absence of NE-100 (1 μM), a well established σ1R antagonist. Cell viability and apoptosis was measured by cytofluorimetric analysis, whereas oxidative stress was evaluated by reduced glutathione (GSH) content and mitochondrial potential analysis.ResultsOur results showed that (+)-pentazocine was able to increase cell viability and restores mitochondrial potential at all concentrations whereas only 1 and 10 μM were able to reduce significantly apoptotic cell death, to restore reduced glutathione intracellular content and prevent ERK1/2 phosphorylation. All these effects were abolished by concomitant treatment with NE-100. Conclusions: (+)-pentazocine exhibits significant dose dependent protective effects in our in vitro model of microglial activation thus suggesting that σ1R may represent a possible strategy for neuroprotection.