Reduction of hippocampal IL-6 levels in LPS-injected rats following acute exendin-4 treatment
| Autor: | Eduarda Dias da Rosa, Angelo Luis Stapassoli Piato, Larissa F. de Oliveira, Érica Zeferino Aguiar, Adriane R. Rosa, Pamela Ferrari, Rosane Gomez, Luiza Paul Géa, Bruna Panizzutti, Rafael Colombo |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Agonist Lipopolysaccharides Male medicine.drug_class Anti-Inflammatory Agents Pharmacology medicine.disease_cause Neuroprotection Hippocampus 03 medical and health sciences 0302 clinical medicine Neurotrophic factors TBARS Medicine Animals Rats Wistar Interleukin 6 Brain-derived neurotrophic factor Inflammation biology Dose-Response Relationship Drug business.industry Interleukin-6 Interleukin General Medicine Rats Disease Models Animal Oxidative Stress 030104 developmental biology Neuroprotective Agents biology.protein Exenatide business 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Naunyn-Schmiedeberg's archives of pharmacology. 393(7) |
| ISSN: | 1432-1912 |
| Popis: | Preclinical evidence on the role of glucagon-like peptide-1 receptor (GLP-1r) agonists in the brain led to an increased interest in repurposing these compounds as a therapy for central nervous system (CNS) disorders and associated comorbidities. We aimed to investigate the neuroprotective effects of acute treatment with exendin (EX)-4, a GLP-1r agonist, in an animal model of inflammation. We evaluated the effect of different doses of EX-4 on inflammatory, neurotrophic, and oxidative stress parameters in the hippocampus and serum of lipopolysaccharide (LPS)-injected animals. Male Wistar rats were injected with LPS (0.25 mg/kg i.p.) and treated with different doses of EX-4 (0.1, 0.3, or 0.5 μg/kg i.p.). Sickness behavior was assessed by locomotor activity and body weight, and depressive-like behavior was also evaluated using forced swim test (FST). Brain-derived neurotrophic factor (BDNF), thiobarbituric acid reactive species (TBARS), and interleukin (IL)-6 were quantified in the serum and hippocampus. Glycemia was also analyzed pre- and post-EX-4 treatment. LPS groups exhibited decreased frequency of crossing and reduced body weight (p 0.001), while alterations on FST were not observed. The higher dose of EX-4 reduced IL-6 in the hippocampus of LPS-injected animals (p = 0.018), and EX-4 per se reduced TBARS serum levels with a modest antioxidant effect in the LPS groups (p ≤ 0.005). BDNF hippocampal levels seemed to be increased in the LPS+EX-4 0.5 group compared with LPS+Saline (p 0.05). Our study provides evidence on acute anti-inflammatory effects of EX-4 in the hippocampus of rats injected with LPS, contributing to future studies on repurposing compounds with potential neuroprotective properties. |
| Databáze: | OpenAIRE |
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