Some aspects of cardiac antioxidant defence: Ebselen (PZ 51) treatment increases glutathione peroxidase activity in the rat heart

Abstract

Ebselcn (PZ 5 1 : 2-phenyl1.2-benzisoelenazol-3-( 2H)-one 1 is ii synthetic organoselenium compound with anti-inflammatory activity ( I . 21, which exhibits glutathione peroxidase (GSH-Px)-like activity, catalysing the reduction o f hydrogen peroxide as well as other organic peroxides [3-5]. Its antiinflammatory effect may be mediated by either the GSH-Px activity, the inhibition of leukotriene B4 formation [6], the antioxidant capacity, or a combination of all of them. Many attempts have been made to increase the antioxidant capacity of the myocardium, since free radical generation has been demonstrated in ischaemia-reperfusion damage [7, 81; superoxide dismutase (SOD) and catalase have been used to decrease myocardial reperfusion injury [9]. Moreover, glutathione (GSH) decreases in the myocardium under ischaemic conditions [ 101 and a possible involvement of the myocardial mitochondria1 pool of GSH has also been recently discussed ( I 1 1. This evidence and hypothesis led us to investigate some aspects of the cardiac antioxidant defence, as well as the effect of Ebselen treatment on the peroxidase activity of the myocardium, which are preliminary results necessary for a rationale of the use of Ebselen to prevent or ameliorate ischaemic or reperfusion damage.