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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

TNF-α immunohistochemical staining (IHCX400) of aortic sections in different experimental groups.(A) Control non-diabetic group with focal faint TNF-a immunostaining (brownish color), (B) Non-diabetic/CRS vehicle-treated group shows moderate diffuse immunostaining, (C) Non-diabetic/CRS fluoxetine-treated and (D) Non-diabetic/CRS imipramine-treated groups show focal mild staining, (E) Control diabetic group (F) Diabetic/CRS vehicle-treated group shows strong diffuse immunostaining, (G) Diabetic/CRS fluoxetine-treated group shows focal mild staining and (H) Diabetic/CRS imipramine-treated group show moderate diffuse immunostaining.
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pone.0120559.g010: TNF-α immunohistochemical staining (IHCX400) of aortic sections in different experimental groups.(A) Control non-diabetic group with focal faint TNF-a immunostaining (brownish color), (B) Non-diabetic/CRS vehicle-treated group shows moderate diffuse immunostaining, (C) Non-diabetic/CRS fluoxetine-treated and (D) Non-diabetic/CRS imipramine-treated groups show focal mild staining, (E) Control diabetic group (F) Diabetic/CRS vehicle-treated group shows strong diffuse immunostaining, (G) Diabetic/CRS fluoxetine-treated group shows focal mild staining and (H) Diabetic/CRS imipramine-treated group show moderate diffuse immunostaining.

Mentions: As depicted in Fig 10 and Table 4, exposure to diabetes induced significant increase in aortic immune-staining optical density of TNF-α (F(1, 40) = 10.23, P = 0.0024). Exposure to CRS induced similar effects on immune-staining optical density of TNF-α in non-diabetic and diabetic rats (P<0.01, P<0.05 respectively). Chronic treatment with fluoxetine significantly (F(3,40) = 12.14, P = 0.0051) decreased aortic TNF-α immune-staining in both non diabetic (P<0.05) and diabetic rats (P<0.05), while chronic treatment with imipramine insignificantly affected TNF-α either in non-diabetic or diabetic rats compared to vehicle treated group.


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)

TNF-α immunohistochemical staining (IHCX400) of aortic sections in different experimental groups.(A) Control non-diabetic group with focal faint TNF-a immunostaining (brownish color), (B) Non-diabetic/CRS vehicle-treated group shows moderate diffuse immunostaining, (C) Non-diabetic/CRS fluoxetine-treated and (D) Non-diabetic/CRS imipramine-treated groups show focal mild staining, (E) Control diabetic group (F) Diabetic/CRS vehicle-treated group shows strong diffuse immunostaining, (G) Diabetic/CRS fluoxetine-treated group shows focal mild staining and (H) Diabetic/CRS imipramine-treated group show moderate diffuse immunostaining.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4380417&req=5

pone.0120559.g010: TNF-α immunohistochemical staining (IHCX400) of aortic sections in different experimental groups.(A) Control non-diabetic group with focal faint TNF-a immunostaining (brownish color), (B) Non-diabetic/CRS vehicle-treated group shows moderate diffuse immunostaining, (C) Non-diabetic/CRS fluoxetine-treated and (D) Non-diabetic/CRS imipramine-treated groups show focal mild staining, (E) Control diabetic group (F) Diabetic/CRS vehicle-treated group shows strong diffuse immunostaining, (G) Diabetic/CRS fluoxetine-treated group shows focal mild staining and (H) Diabetic/CRS imipramine-treated group show moderate diffuse immunostaining.
Mentions: As depicted in Fig 10 and Table 4, exposure to diabetes induced significant increase in aortic immune-staining optical density of TNF-α (F(1, 40) = 10.23, P = 0.0024). Exposure to CRS induced similar effects on immune-staining optical density of TNF-α in non-diabetic and diabetic rats (P<0.01, P<0.05 respectively). Chronic treatment with fluoxetine significantly (F(3,40) = 12.14, P = 0.0051) decreased aortic TNF-α immune-staining in both non diabetic (P<0.05) and diabetic rats (P<0.05), while chronic treatment with imipramine insignificantly affected TNF-α either in non-diabetic or diabetic rats compared to vehicle treated group.

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