Title

 

Authors

R. Di Paola¹, E. Mazzon¹, I. Paterniti², D. Impellizzeri², P. Bramanti¹ and S. Cuzzocrea<sup>1,2

1</sup> IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy.
²Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy.

 

Abstract

During ischemia and reperfusion, the vascular wall, produces multiple ROS, such as O₂⁻, H₂O₂, OH as well as reactive nitrogen species, e.g. ONOO⁻(Li and Jackson, 2002).These molecules derived fromdiverse cellular and molecular sources in vessels, and if present in physiological concentrations, have important functions in homeostasis. There are many potential sources of cellular O₂⁻, including membrane andmitochondrial NAD(P)H oxidases, cyclooxygenase, cytochrome P450, xanthine oxidase(XO) and nitric oxide synthase (NOS), and a lot of substances have been researched in order to find a way to inhibit production of ROS, and thus protect the body from diseases. The inhibition of NAD (P) H oxidases represents an attractive therapeutic target for the treatment of many diseases. Recent studies have shown that nicotinamide adenosine dinucleotide phosphate (NADPH) oxidases are major sources of ROS in cardiomyocytes, smooth muscle cells, endothelial cells, and fibroblasts (Johnson et al., 2002). The apocynin (4-hydroxy-3-methoxyacetophenone, trivial names: apocynin, acetovanillone) was first described by Schmiedeberg in 1883 and was isolated from the roots of Apocynum cannabinum (Canadian hemp), and extracts of it were used as official remedies for dropsy and heart troubles. Apocynin is a reversible inhibitor of NAD(P)H oxidase activity that impedes assembly of the p47phox subunit with the membrane complex (Meyer et al., 1999). It has been used as an efficient inhibitor of the complex NADPH-oxidase in many experimental models (Zhang et al., 2005). The mode of action of apocynin, however, is elusive,a large body of literature suggests that apocynin predominantly acts as an NADPH oxidase inhibitor in vascular systems, but recent study suggest that apocynin shouldbe used as an anti-inflammatory compound (Heumuller et al., 2008). In fact it has been shown in experimental models that apocynin is a potent drug in the treatment of inflammatory disease such as colitis, rheumatoid arthritis and ischemia reperfusion lung injury (Dodd-o et al., 2004). Thus the aim of this study was to investigate the effect of Apocynin, in experimental model of myocardial ischemia. Myocardial I/R injury was caused by clamping the LAD (left anterior descending) coronary artery for 20 min followed by release of the clamp allowing reperfusion for 1 h. Administration of apocynin i.p. (5mg/kg i.p. 10%DMSO) 15 min after ischemia significantly reduced the: (I) histological evidence of myocardial injury(II) pro-inflammatory cytokines (TNF-α, IL-1b) (III) adhesion molecules (ICAM-1, P-Selectin), (IV) nitrotyrosine formation, (V) NF-kB expression (VI) PAR formation and (VII) apoptosis (Bax, Bcl-2, Fas-L and tunel). Finally we report here that treatment of rats with the apocynin caused a substantial reduction in the infarct size caused by regional myocardial ischemia and reperfusion. In conclusion, in this work, we demonstrate that apocynin, reduces myocardial ischemia reperfusion injury, assuming that its beneficial effects are mainly related to its antioxidant properties.

Li C and Jackson RM (2002)  American journal of physiology 282(2):C227-241.
Johnson DK, et al. (2002)  Endothelium 9(3):191-203.
Meyer JW, et al. (1999)  Endothelium 7(1):11-22.
Zhang Y, et al (2005)  American journal of hypertension 18(7):910-916.
Heumuller S, et al. (2008)  Hypertension 51(2):211-217.
Dodd-o JM, et al (2004) Am J Physiol Heart Circ Physiol 287(2):H927-936.