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Octreotide ameliorates inflammation and apoptosis in acute and kindled murine PTZ paradigms

Abstract

In the present study, the role of octreotide (OCT) in pentylenetetrazole (PTZ) kindling as well as in acute convulsion models was evaluated. Mice were allocated in groups as (1) control saline; (2) acute PTZ (PTZ-a; 60 mg/kg, i.p.), as a single convulsive dose; and (3) kindled (PTZ-k) receiving nine subconvulsive doses of PTZ (40 mg/kg, i.p.) for 17 days. Groups 4–7 received either valproic acid (VPA) 50 mg/kg or OCT (50 μg/kg, Sandostatin®) 30 min by oral gavage before PTZ-a or PTZ-k. The median seizure stage, latency onset of first stage 4/5 seizures, and incidence of convulsing animals were recorded. Cortical dopamine (DA), tumor necrosis factor (TNF)-α, interleukin (IL)-10, caspase (Casp)-3, myeloperoxidase (MPO), and nitric oxide (NO) were assessed in addition to inducible nitric oxide synthase (iNOS) that was evaluated immunohistochemically in a different set of groups. OCT halted PTZ-induced epilepsy delaying convulsion latency via modulating MPO and TNF-α and normalizing IL-10 with both treatment regimens. In PTZ-k, it decreased Casp-3 activity, NO level, and iNOS immunoreactivity. OCT in both paradigms decreased DA concentration. The current investigation implicates a crucial role for OCT in modulating PTZ-induced kindling by regulating inflammatory and apoptotic effects.

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Abbreviations

Casp-3:

Caspase-3

DA:

Dopamine

iNOS:

Inducible nitric oxide synthase

IL-10:

Interleukin 10

MPO:

Myeloperoxidase

NO:

Nitric oxide

OCT:

Octreotide

PTZ:

Pentylenetetrazole

SRIF:

Somatotropin release-inhibiting factor

TNF-α:

Tumor necrosis factor

VPA:

Valproic acid

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Correspondence to Noha N. Nassar.

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Al-Shorbagy, M.Y., Nassar, N.N. Octreotide ameliorates inflammation and apoptosis in acute and kindled murine PTZ paradigms. Naunyn-Schmiedeberg's Arch Pharmacol 390, 61–68 (2017). https://doi.org/10.1007/s00210-016-1303-x

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  • DOI: https://doi.org/10.1007/s00210-016-1303-x

Keywords

  • Octroetide
  • Valproate
  • Pentylenetetrazole
  • Kindling
  • Epilepsy
  • Mice
  • Cortex
  • Hippocampus
  • Dopamine
  • Tumor necrosis factor
  • Inducible nitric oxide synthase