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Glycine Provokes Lipid Oxidative Damage and Reduces the Antioxidant Defenses in Brain Cortex of Young Rats

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Abstract

Patients affected by nonketotic hyperglycinemia (NKH) usually present severe neurological symptoms and suffer from acute episodes of intractable seizures with leukoencephalopathy. Although excitotoxicity seems to be involved in the brain damage of NKH, the mechanisms underlying the neuropathology of this disease are not fully established. The objective of the present study was to investigate the in vitro effects of glycine (GLY), that accumulate at high concentrations in the brain of patients affected by this disorder, on important parameters of oxidative stress, such as lipid peroxidation (thiobarbituric acid-reactive substances (TBA-RS) and chemiluminescence) and the most important non-enzymatic antioxidant defense reduced glutathione (GSH) in cerebral cortex from 30-day-old rats. GLY significantly increased TBA-RS and chemiluminescence values, indicating that this metabolite provokes lipid oxidative damage. Furthermore, the addition of high doses of the antioxidants melatonin, trolox (soluble vitamin E) and GSH fully prevented GLY-induced increase of lipid peroxidation, indicating that free radicals were involved in this effect. GLY also decreased GSH brain concentrations, which was totally blocked by melatonin treatment. Finally, GLY significantly reduced sulfhydryl group content from a commercial GSH solution, but did not oxidize reduced cytochrome C. Our data indicate that oxidative stress elicited in vitro by GLY may possibly contribute at least in part to the pathophysiology of the neurological dysfunction in NKH.

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Acknowledgements

This work was supported by grants from CNPq, PRONEX II, FAPERGS, PROPESQ/UFRGS, and FINEP research grant Rede Instituto Brasileiro de Neurociência (IBN-Net) # 01.06.0842-00.

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Authors and Affiliations

  1. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Rua Ramiro Barcelos, 2600 – Anexo, CEP 90035-003, Porto Alegre, RS, Brazil

    Guilhian Leipnitz, Alexandre F. Solano, Bianca Seminotti, Alexandre U. Amaral, Carolina G. Fernandes, Ana Paula Beskow, Carlos S. Dutra Filho & Moacir Wajner

  2. Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Moacir Wajner

  3. Universidade Luterana do Brasil, Canoas, RS, Brazil

    Moacir Wajner

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  1. Guilhian Leipnitz
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  2. Alexandre F. Solano
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  3. Bianca Seminotti
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  4. Alexandre U. Amaral
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  5. Carolina G. Fernandes
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  6. Ana Paula Beskow
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  7. Carlos S. Dutra Filho
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  8. Moacir Wajner
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Correspondence to Moacir Wajner.

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Leipnitz, G., Solano, A.F., Seminotti, B. et al. Glycine Provokes Lipid Oxidative Damage and Reduces the Antioxidant Defenses in Brain Cortex of Young Rats. Cell Mol Neurobiol 29, 253–261 (2009). https://doi.org/10.1007/s10571-008-9318-6

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