Sitagliptin enhances the neuroprotective effect of pregabalin against pentylenetetrazole-induced acute epileptogenesis in mice: Implication of oxidative, inflammatory, apoptotic and autophagy pathways

Sitagliptin enhances the neuroprotective effect of pregabalin against pentylenetetrazole-induced... The current investigation aimed at studying the anti-epileptogenic effect of sitagliptin. The possible effect of the drug in combination with pregabalin in pentylenetetrazole (PTZ)- induced seizures was studied. In addition, the postulated mechanisms that could mediate such effect were explored namely, suppression of oxidative stress and neuro-inflammatory markers, autophagy and apoptosis. Seven days prior to PTZ (60 mg/kg, sc) injection, mice were treated with sitagliptin (5, 15, and 60 mg/kg, twice daily, orally) or pregabalin (30 mg/kg, once daily, orally) or their combination. At the end of the experiment, several parameters were assessed including: oxidative/nitro-oxidative stress such as superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GP-x) catalase (CAT), and lipid peroxidation assessed as malondialdehyde (MDA), nitrate/nitrite (NOx), 3-nitrotyrosine (3-NT). Seizure latency was evaluated. Neuronal damage was also assessed by performing tissue staining by hematoxylin and eosin, estimating hippocampus level of glutamate, gamma-aminobutyric acid (GABA), glial fibrillary acidic protein (GFAP) and brain-derived neurotrophic factor (BDNF). Also, markers for inflammation, autophagy and apoptosis were measured, nuclear factor erythroid-derived 2- like 2 (Nrf2), nuclear factor kappa-B (NF-κB), phosphatidylethanolamine-conjugated form of microtubule-associated protein light chain-3 (LC3-II), casapase-3, Bcl-2-like protein 4 (BAX) and glucagon like peptide-1 (GLP-1) activity. Sitagliptin significantly suppressed epileptogenesis in PTZ-induced seizures. Sitagliptin counteracted neuronal damage and all biochemical, and histo-chemical alteration induced by PTZ. Also, a more significant protective effect was observed after combination with pregabalin. This study is indicative for the antiepileptogenic potential of sitagliptin with or without pregabalin in the PTZ model of epilepsy which is likely to be through its effect on antioxidant, anti-apoptotic and autophagic pathways. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurochemistry International Elsevier

Sitagliptin enhances the neuroprotective effect of pregabalin against pentylenetetrazole-induced acute epileptogenesis in mice: Implication of oxidative, inflammatory, apoptotic and autophagy pathways

Loading next page...
 
/lp/elsevier/sitagliptin-enhances-the-neuroprotective-effect-of-pregabalin-against-wWI79rk9Fs
Publisher
Elsevier
Copyright
Copyright © 2017 Elsevier Ltd
ISSN
0197-0186
D.O.I.
10.1016/j.neuint.2017.10.006
Publisher site
See Article on Publisher Site

Abstract

The current investigation aimed at studying the anti-epileptogenic effect of sitagliptin. The possible effect of the drug in combination with pregabalin in pentylenetetrazole (PTZ)- induced seizures was studied. In addition, the postulated mechanisms that could mediate such effect were explored namely, suppression of oxidative stress and neuro-inflammatory markers, autophagy and apoptosis. Seven days prior to PTZ (60 mg/kg, sc) injection, mice were treated with sitagliptin (5, 15, and 60 mg/kg, twice daily, orally) or pregabalin (30 mg/kg, once daily, orally) or their combination. At the end of the experiment, several parameters were assessed including: oxidative/nitro-oxidative stress such as superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GP-x) catalase (CAT), and lipid peroxidation assessed as malondialdehyde (MDA), nitrate/nitrite (NOx), 3-nitrotyrosine (3-NT). Seizure latency was evaluated. Neuronal damage was also assessed by performing tissue staining by hematoxylin and eosin, estimating hippocampus level of glutamate, gamma-aminobutyric acid (GABA), glial fibrillary acidic protein (GFAP) and brain-derived neurotrophic factor (BDNF). Also, markers for inflammation, autophagy and apoptosis were measured, nuclear factor erythroid-derived 2- like 2 (Nrf2), nuclear factor kappa-B (NF-κB), phosphatidylethanolamine-conjugated form of microtubule-associated protein light chain-3 (LC3-II), casapase-3, Bcl-2-like protein 4 (BAX) and glucagon like peptide-1 (GLP-1) activity. Sitagliptin significantly suppressed epileptogenesis in PTZ-induced seizures. Sitagliptin counteracted neuronal damage and all biochemical, and histo-chemical alteration induced by PTZ. Also, a more significant protective effect was observed after combination with pregabalin. This study is indicative for the antiepileptogenic potential of sitagliptin with or without pregabalin in the PTZ model of epilepsy which is likely to be through its effect on antioxidant, anti-apoptotic and autophagic pathways.

Journal

Neurochemistry InternationalElsevier

Published: May 1, 2018

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 12 million articles from more than
10,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Unlimited reading

Read as many articles as you need. Full articles with original layout, charts and figures. Read online, from anywhere.

Stay up to date

Keep up with your field with Personalized Recommendations and Follow Journals to get automatic updates.

Organize your research

It’s easy to organize your research with our built-in tools.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

Monthly Plan

  • Read unlimited articles
  • Personalized recommendations
  • No expiration
  • Print 20 pages per month
  • 20% off on PDF purchases
  • Organize your research
  • Get updates on your journals and topic searches

$49/month

Start Free Trial

14-day Free Trial

Best Deal — 39% off

Annual Plan

  • All the features of the Professional Plan, but for 39% off!
  • Billed annually
  • No expiration
  • For the normal price of 10 articles elsewhere, you get one full year of unlimited access to articles.

$588

$360/year

billed annually
Start Free Trial

14-day Free Trial