Protectıve effect of bosentan ınduced by cerebral ıschemıa and reperfusıon ınjury ın rats

Stroke is the third-ranking disease group causing death after coronary heart disease and cancer. Also ischemic stroke is the most common cause of stroke due to cerebrovascular diseases.Apoptosis is one of the most important mechanisms in reperfusion and secondary tissue injury occuring after brain paranchyma ischemia. In cerebral ischemia, there are many factors that start the events leading to cell death. These factors contain free radical production, excitotoxicity, sodium and calcium flow disruption, enzymatic changes, stimulation of the inflamatuar process, the activation of platelets and leukocytes, delayed coagulation, endothelial dysfunction and endothelin (ET) release. The most important factor among these is the excessive increase of intracellular calcium concentration. Excessively increased intracellular calcium concentration leads to a chain of events such as the activation of phospholipases, proteases and endonucleases and the formation of free radicals. In addition, binding of endothelins to ETA and ETB receptors causes activation of intracellular signaling systems. For example, as a result of G proteins stimulation, phospholipase C activation, release of inositol phosphate and diacylglycerol, and increased level of calcium in intracellular stores occur.It is thought that endothelin may play a role in atherosclerosis, hypertension, congestive heart failure, acute coronary ischemic syndromes and acute-chronic renal failure due to a variety of biologic effects of endothelin system.Bosentan, an endothelin receptor, is the competitive antagonist of both ETA and ETB. Today, it is used in the treatment of primary (idiopathic and familial) pulmonary arterial hypertension (PAH). In addition to strong vasodilator effect, it has also been reported that endothelin antagonists have antioxidant properties.In this study, after ischemia-reperfusion procedure, bosentan molecule was regularly given to rats for 5 days. The brain tissues of decapitated rats were histopathologically examined. The levels of oxidant and antioxidant were determined in these brain tissues. It was observed that antioxidant levels and histopathological examinations were in rats given bosentan better than control group rats.A result, this study has showed that bosentan may be an agent which could reduce negative effects resulting from neuronal death associated with ischemic stroke.Keywords: Ischemic stroke, Bosentan, Rat