Behavioural, metabolic, and endothelial effects of the TNF-α suppressor thalidomide on rats subjected to chronic mild stress and fed an atherogenic diet

Ismail, B. ; Aboul-Fotouh, S. ; Mansour, A.A. ; Shehata, H.H. ; Salman, M.I. ; Hassan, O.A. ; Abdel-tawab, A.M. ; Ibrahim, Eman 


Abstract


There is accumulating evidence suggesting that depression is a risk factor for cardiovascular diseases. This study aimed to examine the hypothesis that the proinflammatory cytokine TNF-α would partially explain the link between depression and atherosclerotic endothelial changes. Rats were distributed among 6 groups: (i) control group; (ii) group subjected to chronic mild stress (CMS); (iii) group fed a cholesterol-cholic acid-thiouracil (CCT diet); and (iv) CMS group fed the CCT diet and treated with the vehicle for 8 weeks. The last 2 groups were subjected to CMS-CCT and received thalidomide (THAL) or imipramine (IMIP). Rats were assessed behaviorally (sucrose preference, open field, and forced-swimming tests). TNF-α protein was assessed from the serum, aorta, and liver. Aortic TNF-α gene expression (assessed using RT-PCR), serum lipid profile, and insulin levels were measured. Endothelial function was assessed in isolated aortic rings. The THAL and IMIP groups showed ameliorated CMS-CCT-related behavioral changes. CMS-CCT-induced metabolic and endothelial dysfunctions were improved in the THAL group but were worsened in the IMIP group. RT-PCR showed a significant reduction of aortic TNF-α mRNA expression in the THAL and IMIP treatment groups. These data paralleled the findings for aortic immunohistochemistry. The THAL group, but not the IMIP group, showed improved CMS-CCT-induced changes in the vascular reactivity of the aortic rings. Thus, TNF-α provides a target link between depression, metabolic syndrome, and endothelial dysfunction. This could open a new therapeutic approach to address the comorbidities of depression.


Other data

Issue Date 2014
Journal Canadian Journal of Physiology and Pharmacology 
URI http://research.asu.edu.eg/123456789/206
DOI 5
375-85
http://www.scopus.com/inward/record.url?eid=2-s2.0-84899705456&partnerID=MN8TOARS
92
1205-7541
10.1139/cjpp-2013-0446


Recommend this item

CORE Recommender
16
Citations

14
Views


Items in Ain Shams Scholar are protected by copyright, with all rights reserved, unless otherwise indicated.