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Disruption of Energy Transfer and Redox Status by Sulfite in Hippocampus, Striatum, and Cerebellum of Developing Rats

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Abstract

Patients with sulfite oxidase (SO) deficiency present severe brain abnormalities, whose pathophysiology is not yet elucidated. We evaluated the effects of sulfite and thiosulfate, metabolites accumulated in SO deficiency, on creatine kinase (CK) activity, mitochondrial respiration and redox status in hippocampus, striatum and cerebellum of developing rats. Our in vitro results showed that sulfite and thiosulfate decreased CK activity, whereas sulfite also increased malondialdehyde (MDA) levels in all brain structures evaluated. Sulfite further diminished mitochondrial respiration and increased DCFH oxidation and hydrogen peroxide production in hippocampus. Sulfite-induced CK activity decrease was prevented by melatonin (MEL), resveratrol (RSV), and dithiothreitol while increase of MDA levels was prevented by MEL and RSV. Regarding the antioxidant system, sulfite increased glutathione concentrations in hippocampus and striatum. In addition, sulfite decreased the activities of glutathione peroxidase in all brain structures, of glutathione S-transferase in hippocampus and cerebellum, and of glutathione reductase in cerebellum. In vivo experiments performed with intrahippocampal administration of sulfite demonstrated that this metabolite increased superoxide dismutase activity without altering other biochemical parameters in rat hippocampus. Our data suggest that impairment of energy metabolism and redox status may be important pathomechanisms involved in brain damage observed in individuals with SO deficiency.

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Acknowledgements

This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Programa de Apoio a Núcleos de Excelência (PRONEX II), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Pró-Reitoria de Pesquisa/Universidade Federal do Rio Grande do Sul (PROPESQ/UFRGS), Financiadora de estudos e projetos (FINEP), Rede Instituto Brasileiro de Neurociência (IBN-Net) # 01.06.0842-00 and Instituto Nacional de Ciência e Tecnologia em Excitotoxicidade e Neuroproteção (INCT-EN).

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  1. Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos N° 2600 - Attached, Porto Alegre, RS, CEP: 90035-003, Brazil

    Leonardo de Moura Alvorcem, Mateus Struecker da Rosa, Nícolas Manzke Glänzel, Belisa Parmeggiani, Mateus Grings, Felipe Schmitz, Angela T.S. Wyse, Moacir Wajner & Guilhian Leipnitz

  2. Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal de Rio Grande do Sul, Rua Ramiro Barcelos N° 2600 - Attached, Porto Alegre, RS, CEP 90035-003, Brazil

    Angela T.S. Wyse, Moacir Wajner & Guilhian Leipnitz

  3. Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, CEP 90035-903, Brazil

    Moacir Wajner

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  1. Leonardo de Moura Alvorcem
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  2. Mateus Struecker da Rosa
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  7. Angela T.S. Wyse
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  9. Guilhian Leipnitz
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Correspondence to Guilhian Leipnitz.

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The experimental protocol was approved by the Ethics Committee for Animal Research of the UFRGS, Porto Alegre, Brazil, and followed the “National Institutes of Health Guide for the Care and Use of Laboratory Animals” (NIH Publications No. 80–23, revised 1978)

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de Moura Alvorcem, L., da Rosa, M.S., Glänzel, N.M. et al. Disruption of Energy Transfer and Redox Status by Sulfite in Hippocampus, Striatum, and Cerebellum of Developing Rats. Neurotox Res 32, 264–275 (2017). https://doi.org/10.1007/s12640-017-9732-y

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