The effect of carvedilol on enhanced ADP-ribosylation and red blood cell membrane damage caused by free radicals

Abstract

Our results show that carvedilol can modulate the reactive-oxygen-species-induced signaling through poly- and mono(ADP-ribosyl)ation reactions, the NAD(+) catabolism in postischemic perfused hearts and has a marked scavenger effect on free radical generator-induced red blood cell membrane damage. All these findings may play an important role in the beneficial effects of carvedilol treatment in different cardiovascular diseases.

The Role of Akt and Mitogen-Activated Protein Kinase Systems in the Protective Effect of Poly(ADP-Ribose) Polymerase Inhibition in Langendorff Perfused and in Isoproterenol-Damaged Rat Hearts

“…Single-strand DNA brakes can activate the nuclear PARP, which ADP-ribosylates different nuclear proteins at the expense of cleaving NAD ϩ . If PARP activation exceeds a certain limit, it can lead to cellular NAD ϩ and ATP depletion, ultimately resulting in cell death (Habon et al, 2001;Halmosi et al, 2001;Virag and Szabo, 2002;Szabo et al, 2004). We and other investigators have already shown that PARP inhibitors can efficiently reduce oxidative myocardial damage during ischemia-reperfusion both in isolated heart perfusion and in in vivo myocardial infarction models (Zingarelli et al…”

“…Reactive oxygen species and peroxynitrite formation expedites the ischemia-reperfusion-induced cardiac injury and causes lipid peroxidation, protein oxidation, and single-strand DNA brakes (Habon et al, 2001;Halmosi et al, 2001). Single-strand DNA brakes can activate the nuclear PARP, which ADP-ribosylates different nuclear proteins at the expense of cleaving NAD ϩ .…”

Influence of Carvedilol on Superoxide Generation and Enzyme Release From Stimulated Human Neutrophils

“…CARV (at a dose range 1-10 nmol/l) significantly prevented activated neutrophil-induced cardiomyocyte apoptosis on cultured primary neonatal rat cardiomyocytes, possibly due to its antioxidant properties 17 . CARV inhibited oxidative stress in neutrophils and mononuclear cells in patients with hypertension 18 and exerted a marked scavenger effect on free radical generation-induced red blood cell membrane damage 19 . CARV inhibits luminol-enhanced chemiluminiscence of reactive oxygen metabolites in vitro.…”

Neutrophils superoxide anion generation during carvedilol therapy in patients with stable angina

“…This function is attributed to the presence of carbasole moiety in the drug molecule [12]. Carvedilol antioxidative action was demonstrated in vitro and in vivo studies, both in animal and human models [28][29][30][31]. The drug reduced significantly the infarction area in animals with provoked myocardial ischaemia, particularly in those cases where there came to reperfusion proceeding with reactive oxygen species (ROS), which affected the extension and progression of the infarction area.…”