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- Title
Behavioural, metabolic, and endothelial effects of the TNF-α suppressor thalidomide on rats subjected to chronic mild stress and fed an atherogenic diet.
- Authors
Ismail, Basma; Aboul-Fotouh, Sawsan; Mansour, Amal A.; Shehata, Hanan H.; Salman, Manal I.; Ibrahim, Eman A.; Hassan, Olfat A.; Abdel-tawab, Ahmed M.
- 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.
- Subjects
TUMOR necrosis factors; THALIDOMIDE; CARDIOVASCULAR diseases risk factors; MESSENGER RNA; MENTAL depression; IMIPRAMINE; INSULIN resistance; VASCULAR endothelium; DISEASES
- Publication
Canadian Journal of Physiology & Pharmacology, 2014, Vol 92, Issue 5, p375
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/cjpp-2013-0446