Immunohistochemical assesment of Reloxifen and atorvastatin for prevention of postmenopozal atherosclerosis in ovariectomized rats

SUMMARYThe postmenopausal state and the coexisting disorders especially atheroscleroticprocess and its end point cardiovascular diseases are one of the major problems onwhich the scientiests are seeking for better medications to be used. Fort his reasonwe desıgned a study ın which the effects of two drugs raloxifen and atorvastatin onthe process of atherosclerosis are looked for. Our study was performed at animalexperimantal laboratories of Celal Bayar University, on four seperate animal groups,each of them consisting of ten rats. After the rats get into menapausal state followingovariectomy, one group is treated with Evista (Raloksifen) 3mg/kg alone, the othergroup with Ator (Atorvastatin) 30mg/kg alone and the last group with Evista(Raloksifen) and Ator (Atorvastatin) together. After five weeks of treatment and thedecapitation of the rats are completed, the aortas of these animals are fixatedfollowing dissection. The fixated aortas are stained with hemotoxylen and eosine,and with immunohistochemical methods. On the prepared specimens we search forthe markers which play important roles at the atherosclerotic process, such aseostrogen receptor alfa (ERα), eostrogen receptor beta (ERβ), iNOS, eNOS, TNFα,ET-1, MCP-1 which are found on the endothelial cells of the vascular bed.The immunoreactivity of ERβ was highly detectable on endothelial cells of the controlgroup where as ERα immunoreactivity was not detectable. And also eNOSimmunoreactivity was found to be more than the iNOS immunoreactivity. Theimmunostaining of ET-1 was denser corresponding to the staining of NOS. We foundintermediate staining activity of TNFα and MCP-1 which sustain the migration of themonocytes.In the examination of the endothelium of the aortas of the group treated withAtorvastatin ERβ statining was weaker compared with the control group. Also theimmunostaining of the iNOS and eNOS activity was reduced compared to the controlgroup. TNFα, ET-1, MCP-1 levels were also reduced with the administration ofAtorvastatin.The analysis of the endothelium of the group treated with raloxifen reveals minimaldecrease in the immunoreactivity of ERβ, TNFα, ET-1. MCP-1 and also eNOSactivity was found to have no difference but iNOS activity was increased despite theuse of raloxifen.At the group which was treated with both Atorvastatin and raloxifen we detected adecline in the immunoreactivity of all markers especially with TNFα and ET-1staining. But MCP-1 immunoreactivity seems to reveal no difference.