Monoamine oxidase-induced hydroxyl radical production and cardiomyocyte injury during myocardial ischemia–reperfusion in rats

Abstract

To elucidate the involvement of monoamine oxidase (MAO) in hydroxyl radical production and cardiomyocyte injury during ischemia as well as after reperfusion, we applied microdialysis technique to the heart of anesthetized rats. Dialysate samples were collected during 30 min of induced ischemia followed by 60 min of reperfusion. We monitored dialysate 3,4-dihydrobenzoic acid (3,4-DHBA) concentration as an index of hydroxyl radical production using a trapping agent (4-hydroxybenzoic acid), and dialysate myoglobin concentration as an index of cardiomyocyte injury in the ischemic region. The effect of local administration of a MAO inhibitor, pargyline, was investigated. Dialysate 3,4-DHBA concentration increased from 1.9 ± 0.5 nM at baseline to 3.5 ± 0.7 nM at 20-30 min of occlusion. After reperfusion, dialysate 3,4-DHBA concentration further increased reaching a maximum (4.5 ± 0.3 nM) at 20-30 min after reperfusion, and stabilized thereafter. Pargyline suppressed the averaged increase in dialysate 3,4-DHBA concentration by ∼72% during occlusion and by ∼67% during reperfusion. Dialysate myoglobin concentration increased from 235 ± 60 ng/ml at baseline to 1309 ± 298 ng/ml at 20-30 min after occlusion. After reperfusion, dialysate myoglobin concentration further increased reaching a peak (5833 ± 1017 ng/ml) at 10-20 min after reperfusion, and then declined. Pargyline reduced the averaged dialysate myoglobin concentration by ∼56% during occlusion and by ∼41% during reperfusion. MAO plays a significant role in hydroxyl radical production and cardiomyocyte injury during ischemia as well as after reperfusion.

Serotonin uptake via plasma membrane monoamine transporter during myocardial ischemia‐reperfusion in the rat heart in vivo

“…This effect was not observed by inhibition of SERT (Du et al, 2017), moreover it was similar to the effect of MAO inhibition by pargyline as we reported previously (Du et al, 2017). We have also demonstrated MAO-dependent production of hydroxyl radical in the heart during ischemia and reperfusion (Inagaki et al, 2016). These findings suggest that PMAT is involved in the MAO-dependent deleterious effects in the reperfusion-induced cellular injury (Bianchi et al, 2005;Kaludercic et al, 2011).…”

Myocardial interstitial levels of serotonin and its major metabolite 5-hydroxyindole acetic acid during ischemia-reperfusion

“…We have recently demonstrated that local administration of pargyline decreased the production of hydroxyl radical and myoglobin efflux as an index of myocardial cell injury in the region restricted around the dialysis fiber (12). Moreover, although fluoxetine is a selective SERT inhibitor, high-dose fluoxetine may inhibit the NE transporter at cardiac sympathetic nerve endings (25).…”

Ischemia/Reperfusion

“…These include two enzymes localized to the mitochondrial outer membrane, p66 Shc and monoamine oxidase (MAO) (118, 194, 367, 790) (Fig. 8).…”

“…These enzymes normally function to oxidatively deaminate monoamine neurotransmitters and dietary tyramines, producing aldehydes and hydrogen peroxide (193, 194, 205). However, there is an emerging body of evidence indicating that MAOs also contribute to oxidative stress in cardiac I/R injury (70, 367, 408, 409, 817). …”