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Effects of Octreotide in Chronically Mild Stressed Rats: Possible Role of Immune and Oxidative Stress Pathways

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Abstract

Impairment of neuroendocrine, immune and antioxidant defenses contribute to pathophysiology of stress-induced depression. Somatostatin executes diverse regulatory effects on endocrine, exocrine and neural functions; however, the possibility that octreotide, a synthetic somatostatin analogue might mitigate stress-induced depression remains elusive. Hence, the current study aimed to explore the immunomodulatory and antioxidant effects of octreotide in a model of chronic mild stress (CMS). This paradigm was performed by exposing rats to a combination of mild unpredictable stressors for 21 days. Fifty male Wistar rats were divided into five groups; (1) control receiving saline, (2) octreotide given to normal unstressed animals. The remaining three groups were subjected to (3) CMS alone or in combination with octreotide (4) 50 μg/kg or (5) 90 μg/kg. Octreotide increased sucrose preference index and attenuated CMS-induced increases in plasma adrenocorticotrophic hormone and corticosterone levels. In addition, octreotide decreased plasma tumor necrosis factor-alpha concentration. Moreover, it prevented CMS-induced oxidative damage by enhancing the antioxidant defenses superoxide dismutase, glutathione reductase and glutathione in the hippocampus. Furthermore, octreotide normalized the elevated malondialdehyde and lactate dehydrogenase levels in the hippocampus. These results demonstrate a possible antidepressant-like activity of octreotide in CMS due to its antioxidant/antiinflammatory aptitude.

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Abbreviations

ACTH:

Adrenocorticotrophic hormone

CMS:

Chronic mild stress

CORT:

Corticosterone

CRF:

Corticotrophin-releasing factor

CRH:

Corticotrophin-releasing hormone

DTNB:

5,5′-dithiobis-(2-nitrobenzoic acid)

GR:

Glutathione reductase

GSH:

Glutathione

HPA:

Hypothalamic-pituitary–adrenal axis

LDH:

Lactate dehydrogenase

MDA:

Malondialdehyde

NADPH:

Nicotinamide adenine dinucleotide phosphate

NADP:

Nicotinamide adenine dinucleotide

NF-KB:

Nuclear factor-kappa B

OCT:

Octreotide

PVN:

Paraventricular nucleus

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

SP:

Sucrose preference

SRIF:

Somatotropin release inhibiting factor

TBA:

Trichloroacetic acid-thiobarbituric acid

TNF-α:

Tumor necrosis factor-alpha

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Authors and Affiliations

  1. Biochemistry Department, Faculty of Pharmacy, Misr International University, Cairo, Egypt

    Mona F. Schaalan

  2. Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt

    Noha N. Nassar

Authors
  1. Mona F. Schaalan
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  2. Noha N. Nassar
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Correspondence to Noha N. Nassar.

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Schaalan, M.F., Nassar, N.N. Effects of Octreotide in Chronically Mild Stressed Rats: Possible Role of Immune and Oxidative Stress Pathways. Neurochem Res 36, 1717–1723 (2011). https://doi.org/10.1007/s11064-011-0486-2

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  • DOI: https://doi.org/10.1007/s11064-011-0486-2

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