Selective A2A receptor antagonist SCH 58261 modulates striatal oxidative stress and alleviates toxicity induced by 3-Nitropropionic acid in male Wistar rats.

Abstract

The aim of the present study was to investigate the effects of SCH58261, a selective adenosine A2A receptor antagonist, on striatal toxicity induced by 3-nitropropionic acid (3-NP) in rats. The experimental protocol consisted of 10 administrations (once a day) of SCH58261 (0.01 or 0.05 mg/kg/day, intraperitoneal, i.p.). From 7th to 10th day, 3-NP (20 mg/kg/day, i.p.) was injected 1 h after SCH58261 administration. Twenty-four hours after the last 3-NP injection, the body weight gain, locomotor activity (open-field test), motor coordination (rotarod test), striatal succinate dehydrogenase (SDH) activity and parameters linked to striatal oxidative status were evaluated in rats. The marked body weight loss resulting from 3-NP injections in rats was partially protected by SCH 58261 at both doses. SCH 58261 at the highest dose was effective against impairments on motor coordination and locomotor activity induced by 3-NP. SCH 58261 was unable to restore the inhibition of SDH activity caused by 3-NP. In addition, the increase in striatal reactive species (RS) levels, depletion of reduced glutathione (GSH) content and stimulation of glutathione reductase (GR) activity provoked by 3-NP injections were alleviated by both doses of SCH 58261. The highest dose of SCH 58261 was also effective in attenuating the increase of protein carbonyl levels as well as the inhibition of glutathione peroxidase (GPx) activity in rats exposed to 3-NP. Our results revealed that reduction of oxidative stress in rat striatum by adenosine A2A receptor antagonism contributes for alleviating 3-NP-induced toxicity.

• Authors: Cristiani F Bortolatto, Angélica S Reis, Mikaela P Pinz, Guilherme T Voss, Renata L Oliveira, Ane G Vogt, Silvane Roman, Cristiano R Jesse, Cristiane Luchese, Ethel A Wilhelm
• Journal: Metabolic brain disease (Metab Brain Dis) Vol. 32 Issue 6 Pg. 1919-1927 (12 2017) ISSN: 1573-7365 [Electronic] United States
• PMID: 28795281 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine
• Adenosine A2 Receptor Antagonists
• Neuroprotective Agents
• Nitro Compounds
• Propionates
• Pyrimidines
• Reactive Oxygen Species
• Triazoles
• Glutathione
• 3-nitropropionic acid

Topics

• Adenosine A2 Receptor Antagonists (pharmacology)
• Animals
• Corpus Striatum (drug effects, metabolism)
• Glutathione (metabolism)
• Male
• Motor Activity (drug effects)
• Neuroprotective Agents (pharmacology)
• Nitro Compounds (pharmacology)
• Oxidative Stress (drug effects)
• Propionates (pharmacology)
• Pyrimidines (pharmacology)
• Rats
• Rats, Wistar
• Reactive Oxygen Species (metabolism)
• Rotarod Performance Test
• Triazoles (pharmacology)