Pirlindole and dehydropirlindole protect rat cultured neuronal cells against oxidative stress‐induced cell death through a mechanism unrelated to MAO‐A inhibition

Abstract

1 It has been shown that the MAO (monoamine oxidase)-B inhibitor deprenyl (DPR, selegiline) protects some cell types against oxidative stress. By decreasing H 2 O 2 production, MAO-A inhibitors could also reduce oxidative stress. 2 This study reports the eect of the MAO-A inhibitors, pirlindole (PIR), dehydropirlindole (DHP), brofaromine (BRO) and moclobemide (MCL) on primary-cultured brain cells exposed to iron-mediated toxicity. A comparison with trolox (TRO), a hydrosoluble vitamin-E analogue that protects against such an induced stress, was performed. 3 Rat hippocampal or cortical cultured cells were exposed either to 2 mM FeSO 4 alone or in the presence of PIR, DHP, BRO, DPR, MCL or TRO. Cell survival (lactate-dehydrogenase measurements, 16 h incubation), intracellular peroxide production (DCF-¯uorescence, 1 h incubation), lipoperoxidation (TBARS-¯uorescence, 6 h incubation) and mitochondrial function (MTT-test, 16 h incubation) were assessed. 4 PIR, DHP and TRO signi®cantly protected cultures (P50.05) against Fe 2+ -induced toxicity in a concentration-dependent manner. The EC 50s of these compounds were 6, 12 and 19 mM, respectively, in hippocampal cells. For cortical cell cultures incubated in the presence of iron and PIR or DHP, EC 50s were 5 and 6 mM respectively. All Hill coecients were close to unity. BRO, MCL and DPR were not protective in any type of culture. The IC 50s for the inhibition of MAO-A were 2, 2 and 0.2 mM for PIR, DHP and BRO, respectively. PIR, DHP and TRO, but not DPR, induced a signi®cant decrease in both intracellular peroxide production and lipoperoxidation. They also improved mitochondrial function. 5 These experiments show that PIR and DHP can protect hippocampal and cortical neurons against oxidative stress at pharmacologically relevant concentrations. This protective eect seems unrelated to inhibition of MAO-A, but possibly involves free radical scavenging.

Knocking down of the KCC2 in rat hippocampal neurons increases intracellular chloride concentration and compromises neuronal survival

“…One of the factors that might contribute to neuronal loss during the transfection procedure using lipofectamine reagents is oxidative stress (Dokka et al 2000; Kongkaneramit et al 2008). To verify whether reactive oxygen species are, at least in part, responsible for neuronal death in our experimental conditions, we incubated neurons during and after transfection with 100 μ m Trolox, an analogue of vitamin E, frequently used to assess the role of oxidative injury in neuronal cell death (Vergun et al 2001; Boland et al 2002; Quintanilla et al 2005). The application of Trolox significantly reduced loss of neuronal cells expressing either scrambled or silencing shRNAs (Fig.…”

Structure Prediction and Potential Inhibitors Docking of Enterovirus 2C Proteins

“…Pirlindole is an inhibitor of monoamine oxidase A, an enzyme involved in the metabolism of monoamines, including serotonin, melatonin, adrenaline, and noradrenaline (Boland et al, 2002). Zuclopenthixol is an antagonist of D2 dopamine receptors and used for the treatment of psychotic disorders (Faure et al, 2021).…”