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

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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.

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Acknowledgements

We gratefully acknowledge UFPel, UNIFRA, FAPERGS (research grants #16/2551-0000526-5 – PRONUPEQ, # 16/2551-0000240-1 – PRONEM), CAPES and CNPq for the financial support. C.R.J. and C.L. are recipients of CNPq fellowship. M.P.P. is recipients of CAPES fellowship.

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Authors and Affiliations

  1. Programa de Pós-graduação em Bioquímica e Bioprospecção (PPGBio), Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas (UFPel), Campus Capão do Leão, Pelotas, RS, CEP 96010-900, Brazil

    Cristiani F. Bortolatto, Angélica S. Reis, Mikaela P. Pinz, Guilherme T. Voss, Renata L. Oliveira, Ane G. Vogt, Cristiane Luchese & Ethel A. Wilhelm

  2. Universidade Regional Integrada, Campus Erechim, Erechim, RS, CEP 99700-000, Brazil

    Silvane Roman

  3. Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas - LaftamBio Pampa, Universidade Federal do Pampa, Itaqui, RS, CEP 97650-000, Brazil

    Cristiano R. Jesse

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  1. Cristiani F. Bortolatto
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  2. Angélica S. Reis
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  4. Guilherme T. Voss
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  9. Cristiane Luchese
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Correspondence to Cristiani F. Bortolatto or Ethel A. Wilhelm.

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Bortolatto, C.F., Reis, A.S., Pinz, M.P. et al. Selective A2A receptor antagonist SCH 58261 modulates striatal oxidative stress and alleviates toxicity induced by 3-Nitropropionic acid in male Wistar rats. Metab Brain Dis 32, 1919–1927 (2017). https://doi.org/10.1007/s11011-017-0086-1

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