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Arginine administration reduces creatine kinase activity in rat cerebellum

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Abstract

In the present study was evaluated the in vivoeffects of arginine administration on creatine kinase (CK) activity in cerebellum of rats. We also tested the influence of antioxidants, namely α-tocopherol and ascorbic acid and the nitric oxide sinthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME), on the effects elicited by Arg in order to investigate the possible participation of nitric oxide (NO) and/or its derivatives peroxynitrite (ONOO−) and other/or free radicals on the effects of arginine on CK activity. Sixty-day-old rats were treated with a single i.p. injection of saline (control, group I), arginine (0.8 g/Kg) (group II), L-NAME (2.0 mg/Kg or 20.0 mg/Kg) (group III) or Arg (0.8 g/Kg) plus L-NAME (2.0 mg/Kg or 20.0 mg/Kg) (group IV) and were killed 1 h later. In another set of experiments, the animals were pretreated for 1 week with daily i.p. administration of saline (control) or α-tocopherol (40 mg/Kg) and ascorbic acid (100 mg/Kg). Twelve hours after the last injection of the antioxidants, the rats received one i.p. injection of arginine (0.8 g/Kg) or saline and were killed 1 h later. Results showed that total and cytosolic CK activities were significantly inhibited by arginine administration in cerebellum of rats, in contrast to mitochondrial CK activity which was not affected by this amino acid. Furthermore, simultaneous injection of L-NAME (20.0 mg/Kg) and treatment with α-tocopherol and ascorbic acid prevented these effects. The data indicate that the reduction of CK activity in cerebellum of rats caused by arginine was probably mediated by NO and/or its derivatives ONOO−and other free radicals. Considering the importance of CK for the maintenance of energy homeostasis in the brain, if this enzyme inhibition also occurs in hyperargininemic patients, it is possible that CK inhibition may be one of the mechanisms by which arginine is neurotoxic in hyperargininemia.

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Acknowledgement

This work was supported in part by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq – Brazil).

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  1. Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil

    Débora Delwing, Andrea R. Cornélio, Moacir Wajner, Clóvis M. D. Wannmacher & Angela T. S. Wyse

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  1. Débora Delwing
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  2. Andrea R. Cornélio
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Correspondence to Angela T. S. Wyse.

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Delwing, D., Cornélio, A.R., Wajner, M. et al. Arginine administration reduces creatine kinase activity in rat cerebellum. Metab Brain Dis 22, 13–23 (2007). https://doi.org/10.1007/s11011-006-9028-z

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  • DOI: https://doi.org/10.1007/s11011-006-9028-z

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