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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.

Habib M, Shaker S, El-Gayar N, Aboul-Fotouh S - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

ABSTRACT

Unlabelled: 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.

Method: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Pearson's correlation between Ach-induced maximal aortic relaxation response (%) and aortic expression of inflammatory markers, TLR-4 gene (mRNA by RT-PCR), TLR-4 protein, TNF-α and IL-1β at the present study.
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pone.0120559.g008: Pearson's correlation between Ach-induced maximal aortic relaxation response (%) and aortic expression of inflammatory markers, TLR-4 gene (mRNA by RT-PCR), TLR-4 protein, TNF-α and IL-1β at the present study.

Mentions: As shown in Fig 8, statistical analysis by Pearson’s correlation coefficient reveals that Ach-induced maximal aortic relaxation response (%) significantly correlates with aortic expression of inflammatory markers, TLR-4 gene (r2 = -0.707, P < 0.001), TLR-4 protein (r2 = -0.661, P < 0.001), TNF-α (r2 = -0.698, P < 0.001) and IL-1β (r2 = -0.797, P < 0.001).


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.

Habib M, Shaker S, El-Gayar N, Aboul-Fotouh S - PLoS ONE (2015)

Pearson's correlation between Ach-induced maximal aortic relaxation response (%) and aortic expression of inflammatory markers, TLR-4 gene (mRNA by RT-PCR), TLR-4 protein, TNF-α and IL-1β at the present study.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4380417&req=5

pone.0120559.g008: Pearson's correlation between Ach-induced maximal aortic relaxation response (%) and aortic expression of inflammatory markers, TLR-4 gene (mRNA by RT-PCR), TLR-4 protein, TNF-α and IL-1β at the present study.
Mentions: As shown in Fig 8, statistical analysis by Pearson’s correlation coefficient reveals that Ach-induced maximal aortic relaxation response (%) significantly correlates with aortic expression of inflammatory markers, TLR-4 gene (r2 = -0.707, P < 0.001), TLR-4 protein (r2 = -0.661, P < 0.001), TNF-α (r2 = -0.698, P < 0.001) and IL-1β (r2 = -0.797, P < 0.001).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

ABSTRACT

Unlabelled: 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.

Method: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus