BackgroundThe importance of doxorubicin (Dox), as a potent antitumor antibiotic, is limited by the development of life-threatening cardiomyopathy. It has been shown that free radicals are involved in acute doxorubicin-induced toxicity. The aim of this study was to determine the protective effect of vitamin E and telmisartan in acute doxorubicin induced cardiotoxicity.MethodsThirty two male Sprague - Dawly rats were involved in this study and were randomly separated into 4 groups, eight rats in each group, one group received normal saline I.P as control and second group received doxorubicin 20 mg/kg I.P, the other two groups also received doxorubicin 20 mg/kg I.P as single dose after seven cumulative doses (for seven days) of vitamin E (100 mg/kg) and telmisartan (1 mg/kg) respectively. Immunofluorescent staining for monocytes infiltration and analyses of plasma by (ELISAs) for MCP-1and troponin I. Western immunoblotting assay for ICAM-1, while left ventricular function was analyzed by microcatheter, also estimated the level of oxidative stress parameters (MDA and Catalase) and cardiac enzymes activities (CK-MB and LDH) before starting drugs treatment and after treatment period by 48 hours.ResultsThe immunofluorescent staining showed that administration of vitamin E and telmisartan are attenuated of mononuclear cell infiltration; (p < 0.05 vs. Dox group), also reduced the level of chemokines MCP-1 and ICAM-1 expression compared with Dox group only, and there is marked reduction of myocardial troponin-I levels with improved LV function in vitamin E and telmisartan treated group. Doxorubicin treatment increased MDA, LDH, CK-MB levels significantly (P < 0.01), and were counteracted by administration of vitamin E and telmisartan, but did not significantly affect serum catalase activity.ConclusionsAntioxidant effect (Vitamin E and telmisartan) have been shown to decrease doxorubicininduced cardiotoxicity.

Background. Atherosclerosis is characterized by endothelial dysfunction, vascular inflammation, and the buildup of lipids, cholesterol, calcium, and cellular debris within the intima of the walls of large and medium size arteries. Objective. To evaluate the effect of clopidogrel on atherosclerosis progression. Materials and Methods. A total of 28 local domestic rabbits were assigned to four groups: normal control, atherogenic control, vehicle control, and clopidogrel treated. Serum triglycerides, total cholesterol, HDL-C, plasma high sensitive C-reactive protein (hsCRP), plasma malondialdehyde (MDA), and plasma reduced glutathione (GSH) were measured at the end of the experiment. Immunohistochemical of aortic atherosclerotic changes were also performed. Results. There was no statistically significant difference between atherogenic control group and vehicle group. Levels of lipid profile, atherogenic index, hsCRP, and MDA are increased while GSH levels were decreased in animals on atherogenic diet. Immunohistochemical analysis showed that aortic expressions of VCAM-1, MCP-1, TNF-α, and IL-17A were significantly increased in atherogenic control group. Histopathologic finding showed that animals on atherogenic diet have significant atherosclerotic lesion. Compared to atherogenic control group clopidogrel do not have significant effect on lipid profile. Clopidogrel significantly reduces hsCRP and MDA levels and increases GSH level. Furthermore, clopidogrel treatment significantly reduced aortic expressions parameters and the histopathologic examination of the aortic arch showed a significant reduction of atherosclerotic lesion. Conclusions. This study outlines how clopidogrel reduces lipid peroxidation, systemic inflammation, and aortic expression of inflammatory markers and hence reduces the progression of atherosclerosis.

Summary Purpose The objective of this study is to assess the effect of the candesartan on the progression of atherosclerosis through the downregulation of NF‐κβ and interference with oxidative pathway. Methods Twenty‐four rabbits were assigned to three groups: control group fed normal diet; induced untreated group fed 1% cholesterol diet; and treated candesartan group also fed 1% cholesterol diet. Plasma lipid profiles were measured, and ELISA for plasma cytokines and chemokine was performed. Analyses of NF‐κβ and VCAM‐1 were performed using Western blotting with RT‐PCR for NF‐κB activity at mRNA. Doppler ultrasound was used to evaluate aortic intima‐media thickness, and atheroma was detected by H&E staining. Immunofluorescent staining was performed to confirm accumulation of monocytes and PMNs. Results Candesartan markedly reduced the levels of the plasma lipid profile including total cholesterol [TC], triglycerides [TG], and LDL‐C, while significantly elevating levels in the plasma HDL‐C, in addition to reducing cytokine (TNF‐α, IL‐6, IL‐1β) and chemokine levels (MCP‐1). Also, it decreased the aortic malondialdehyde (MDA) concentration and elevated the aortic glutathione (GSH) level compared with untreated animals (P < 0.05). The triplex Doppler ultrasound study confirmed that the candesartan attenuated intima‐media thickness at 6 months of study. All candesartan‐treated rabbits showed significantly attenuated atherosclerosis lesions with reduced accumulation of monocytes and had significantly reduced VCAM‐1 expression and NF‐κβ activity. Conclusion Candesartan retards the progression of atherosclerosis via interference with NF‐κβ and oxidative pathways.

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