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Neuroprotective effects of guanosine administration on behavioral, brain activity, neurochemical and redox parameters in a rat model of chronic hepatic encephalopathy

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Abstract

It is well known that glutamatergic excitotoxicity and oxidative stress are implicated in the pathogenesis of hepatic encephalopathy (HE). The nucleoside guanosine exerts neuroprotective effects through the antagonism against glutamate neurotoxicity and antioxidant properties. In this study, we evaluated the neuroprotective effect of guanosine in an animal model of chronic HE. Rats underwent bile duct ligation (BDL) and 2 weeks later they were treated with i.p. injection of guanosine 7.5 mg/kg once a day for 1-week. We evaluated the effects of guanosine in HE studying several aspects: a) animal behavior using open field and Y-maze tasks; b) brain rhythm changes in electroencephalogram (EEG) recordings; c) purines and glutamate levels in the cerebral spinal fluid (CSF); and d) oxidative stress parameters in the brain. BDL rats presented increased levels of glutamate, purines and metabolites in the CSF, as well as increased oxidative damage. Guanosine was able not only to prevent these effects but also to attenuate the behavioral and EEG impairment induced by BDL. Our study shows the neuroprotective effects of systemic administration of guanosine in a rat model of HE and highlights the involvement of purinergic system in the physiopathology of this disease.

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Acknowledgments

We are grateful to the financial support of FINEP Rede Instituto Brasileiro de Neurociência (IBN-Net) # 01.06.08.42-00, CNPq, CAPES, FAPERGS, UFRGS and Instituto Nacional de Ciência e Tecnologia - Neurotoxicidade e Neuroproteção (INCT-EN).

Conflict of interests

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Programa de Pós-graduação em Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul-UFRGS, Rua Ramiro Barcelos 2600 Anexo, 90035-003, Porto Alegre, RS, Brazil

    L. G. Paniz, M. E. Calcagnotto, D. G. Machado, G. F. Santos, G. Hansel, R. F. Almeida, F. V. Torres, A. M. de Assis, E. P. Rico & D. O. Souza

  2. Departamento de Neurobiologia, Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil

    P. Pandolfo

  3. Instituto de Cardiologia do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

    R. S. Bruch & L. M. Brum

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  1. L. G. Paniz
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  2. M. E. Calcagnotto
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  3. P. Pandolfo
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  4. D. G. Machado
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  5. G. F. Santos
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  6. G. Hansel
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  7. R. F. Almeida
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  8. R. S. Bruch
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  9. L. M. Brum
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  10. F. V. Torres
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  11. A. M. de Assis
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  13. D. O. Souza
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Correspondence to L. G. Paniz or M. E. Calcagnotto.

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Paniz, L.G., Calcagnotto, M.E., Pandolfo, P. et al. Neuroprotective effects of guanosine administration on behavioral, brain activity, neurochemical and redox parameters in a rat model of chronic hepatic encephalopathy. Metab Brain Dis 29, 645–654 (2014). https://doi.org/10.1007/s11011-014-9548-x

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