Valsartan modulates the inflammatory response and apoptosis and protects from cerebral ischemia Reperfusion injury
Objectives: The objective of this study is to investigate the possible cerebroprotective potential of valsartan in brain ischemia reperfusion injury via interfering with inflammation and oxidative pathway and apoptosis. Materials and Methods: Adult albino rats were randomized into four groups as follow: Group (1) sham group: the rats were subjected to the same surgical procedures as other groups but the common carotid arteries were not occluded; Group (2) control (ischemic-reperfused) group: the rats were subjected to the same surgical procedures as other groups with bilateral common carotid artery occlusion (BCCAO) for 30 min. followed by reperfusion for 1 hr but without drug; Group (3) control vehicle group: ten days before surgery, rats received daily the vehicle of valsartan drug, normal saline (0.9% Nacl) (1 ml/kg/day) intraperitoneally, then anesthesia and surgery with BCCAO for 30 min. followed by reperfusion for 1 hr were done and Group (4) valsartan treated group: rats received daily valsartan intraperitoneally. The dose of valsartan was (3 mg/kg /day) for ten days before the surgery, then anesthesia and surgery with BCCAO for 30 min. followed by reperfusion for 1 hr. Results: At the end of the experiment, the levels of cerebral TNF-α, IL-6, IL-10,Caspase- 3,Bax,MDA,CD4 and MPO significantly (p < 0.05) increased in control group as compared with the sham group and the level of cerebral GSH significantly (p < 0.05) decreased in control group as compared with the sham group, while there was insignificant difference in cerebral levels of CD8 between the four experimental groups. Histopothological analysis showed that rats in control group showed significant cerebral injury. Treatment with valsartan significantly counteracted the increase in the cerebral levels of TNF-α, IL-6, IL-10,Caspase-3,Bax,MDA,CD4 and MPO and the decrease of GSH .Histopathological analysis revealed that valsartan significantly (P < 0.05) reduced the severity of cerebral injury in the rats underwent BCCAO. Conclusions: The results of the study revealed that inflammatory cytokines, apoptosis pathways and oxidative stress mediators are involved in global cerebral ischemia induced by bilateral common carotid artery occlusion. Cerebral ischemia reperfusion injury can be modified by valsartan via its anti-inflammatory, anti-apoptosis and anti-oxidant effects.
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