title: The effects of antidepressants "fluoxetine and imipramine" on vascular abnormalities and Toll like receptor-4 expression in diabetic and non-diabetic rats exposed to chronic stress.
abstract: Several studies reveal that diabetes doubles the odds of comorbid depression with evidence of a pro-inflammatory state underlying its vascular complications. Indeed, little information is available about vascular effects of antidepressant drugs in diabetes.
  
  
  METHODS
  We investigated the effect of chronic administration of fluoxetine "FLU" and imipramine "IMIP" on behavioral, metabolic and vascular abnormalities in diabetic and non-diabetic rats exposed to chronic restraint stress (CRS).
  
  
  RESULTS
  Both diabetes and CRS induced depressive-like behavior which was more prominent in diabetic/depressed rats; this was reversed by chronic treatment with FLU and IMIP in a comparable manner. Diabetic and non-diabetic rats exposed to CRS exhibited abnormalities in glucose homeostasis, lipid profile and vascular function, manifested by decreased endothelium-dependent relaxation, increased systolic blood pressure and histopathological atherosclerotic changes. Vascular and metabolic dysfunctions were associated with significant increase in aortic expression of TLR-4, and pro-inflammatory cytokines (TNF-α and IL-1ß). FLU ameliorated these metabolic, vascular and inflammatory abnormalities, while IMIP induced either no change or even worsening of some parameters.
  
  
  CONCLUSIONS
  FLU has favorable effect over IMIP on metabolic, vascular and inflammatory aberrations associated with DM and CRS in Wistar rats, clarifying the preference of FLU over IMIP in management of comorbid depression in diabetic subjects.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Habib
authors.affiliation: Department of Histology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Safaa
authors.initials: S
authors.lastname: Shaker
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Nesreen
authors.initials: N
authors.lastname: El-Gayar
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; Clinical Pharmacology Unit, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Sawsan
authors.initials: S
authors.lastname: Aboul-Fotouh
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005473:Fluoxetine / Q000494:pharmacology*; D007099:Imipramine / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D005473:Fluoxetine; D007099:Imipramine
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