{"title":"2,4,6-三取代-1,3,5-嘧啶对大鼠全脑缺血再灌注脑梗死的脑保护作用研究","authors":"Venkata Satyanarayana Murthy Bendi , Akula Annapurna , Vasudeva Rao Avupati","doi":"10.1016/j.jopr.2013.08.030","DOIUrl":null,"url":null,"abstract":"<div><h3>Background/objectives</h3><p>Cerebral I/R injury is mainly characterized by oxidant production, complement activation, leukocyte–endothelial cell adhesion, platelet–leukocyte aggregation, increased microvascular permeability and decreased endothelium-dependent relaxation. I/R injury can lead to multiorgan dysfunction or death. In recent years, pyrimidines have received much attention of researchers because of their vasodilator, anti-inflammatory and antioxidant properties. Studies on cerebroprotective mechanism of pyrimidine derivatives on cerebral I/R injury are limited. Hence it is worthwhile to study the role of pyrimidines as cerebroprotective agents and evaluated for their possible inherent underlying mechanisms.</p></div><div><h3>Methods</h3><p>Experimental cerebral infarction was produced by bilateral common carotid artery occlusion (global cerebral ischemia) for 30 min followed by 4 h reperfusion in Wistar rats. The oxidative and anti-inflammatory biomarkers were estimated and percentage infarction was determined.</p></div><div><h3>Results and conclusions</h3><p>A dose dependent cerebroprotective action of pyrimidines (AUCP1 and AUCP2) in terms of limiting the infarct size was observed in the present <em>in vivo</em> model of cerebral I/R in Wistar rats. The antioxidant role of pyrimidines (AUCP1 and AUCP2) in cerebroprotection was confirmed by measuring SOD, CAT, MDA, levels. MDA levels were decreased; SOD and CAT levels were increased by treatment with pyrimidines (AUCP1 and AUCP2). The cerebroprotective actions of pyrimidines (AUCP1 and AUCP2) are partially attributed to their anti-inflammatory effects against I/R injury in rats as evidenced by significant reduction in pro-inflammatory markers MPO, TNF-α and significant increase in anti-inflammatory marker IL-10. Pyrimidines (AUCP1 and AUCP2) evaluated in the present investigation has offered significant cerebroprotection against ischemia-reperfusion induced cerebral infarction in rats.</p></div>","PeriodicalId":16787,"journal":{"name":"Journal of Pharmacy Research","volume":"6 9","pages":"Pages 939-944"},"PeriodicalIF":0.0000,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jopr.2013.08.030","citationCount":"1","resultStr":"{\"title\":\"Studies on cerebroprotective potential of 2,4,6-trisubstituted-1,3,5-pyrimidines in global ischemia/reperfusion induced cerebral infarction in rats\",\"authors\":\"Venkata Satyanarayana Murthy Bendi , Akula Annapurna , Vasudeva Rao Avupati\",\"doi\":\"10.1016/j.jopr.2013.08.030\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background/objectives</h3><p>Cerebral I/R injury is mainly characterized by oxidant production, complement activation, leukocyte–endothelial cell adhesion, platelet–leukocyte aggregation, increased microvascular permeability and decreased endothelium-dependent relaxation. I/R injury can lead to multiorgan dysfunction or death. In recent years, pyrimidines have received much attention of researchers because of their vasodilator, anti-inflammatory and antioxidant properties. Studies on cerebroprotective mechanism of pyrimidine derivatives on cerebral I/R injury are limited. Hence it is worthwhile to study the role of pyrimidines as cerebroprotective agents and evaluated for their possible inherent underlying mechanisms.</p></div><div><h3>Methods</h3><p>Experimental cerebral infarction was produced by bilateral common carotid artery occlusion (global cerebral ischemia) for 30 min followed by 4 h reperfusion in Wistar rats. The oxidative and anti-inflammatory biomarkers were estimated and percentage infarction was determined.</p></div><div><h3>Results and conclusions</h3><p>A dose dependent cerebroprotective action of pyrimidines (AUCP1 and AUCP2) in terms of limiting the infarct size was observed in the present <em>in vivo</em> model of cerebral I/R in Wistar rats. The antioxidant role of pyrimidines (AUCP1 and AUCP2) in cerebroprotection was confirmed by measuring SOD, CAT, MDA, levels. MDA levels were decreased; SOD and CAT levels were increased by treatment with pyrimidines (AUCP1 and AUCP2). The cerebroprotective actions of pyrimidines (AUCP1 and AUCP2) are partially attributed to their anti-inflammatory effects against I/R injury in rats as evidenced by significant reduction in pro-inflammatory markers MPO, TNF-α and significant increase in anti-inflammatory marker IL-10. Pyrimidines (AUCP1 and AUCP2) evaluated in the present investigation has offered significant cerebroprotection against ischemia-reperfusion induced cerebral infarction in rats.</p></div>\",\"PeriodicalId\":16787,\"journal\":{\"name\":\"Journal of Pharmacy Research\",\"volume\":\"6 9\",\"pages\":\"Pages 939-944\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2013-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/j.jopr.2013.08.030\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Pharmacy Research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0974694313003654\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Pharmacy Research","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0974694313003654","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Studies on cerebroprotective potential of 2,4,6-trisubstituted-1,3,5-pyrimidines in global ischemia/reperfusion induced cerebral infarction in rats
Background/objectives
Cerebral I/R injury is mainly characterized by oxidant production, complement activation, leukocyte–endothelial cell adhesion, platelet–leukocyte aggregation, increased microvascular permeability and decreased endothelium-dependent relaxation. I/R injury can lead to multiorgan dysfunction or death. In recent years, pyrimidines have received much attention of researchers because of their vasodilator, anti-inflammatory and antioxidant properties. Studies on cerebroprotective mechanism of pyrimidine derivatives on cerebral I/R injury are limited. Hence it is worthwhile to study the role of pyrimidines as cerebroprotective agents and evaluated for their possible inherent underlying mechanisms.
Methods
Experimental cerebral infarction was produced by bilateral common carotid artery occlusion (global cerebral ischemia) for 30 min followed by 4 h reperfusion in Wistar rats. The oxidative and anti-inflammatory biomarkers were estimated and percentage infarction was determined.
Results and conclusions
A dose dependent cerebroprotective action of pyrimidines (AUCP1 and AUCP2) in terms of limiting the infarct size was observed in the present in vivo model of cerebral I/R in Wistar rats. The antioxidant role of pyrimidines (AUCP1 and AUCP2) in cerebroprotection was confirmed by measuring SOD, CAT, MDA, levels. MDA levels were decreased; SOD and CAT levels were increased by treatment with pyrimidines (AUCP1 and AUCP2). The cerebroprotective actions of pyrimidines (AUCP1 and AUCP2) are partially attributed to their anti-inflammatory effects against I/R injury in rats as evidenced by significant reduction in pro-inflammatory markers MPO, TNF-α and significant increase in anti-inflammatory marker IL-10. Pyrimidines (AUCP1 and AUCP2) evaluated in the present investigation has offered significant cerebroprotection against ischemia-reperfusion induced cerebral infarction in rats.
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