In vitro evidence that sulfite impairs glutamatergic neurotransmission and inhibits glutathione metabolism-related enzymes in rat cerebral cortex

International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience
Belisa ParmeggianiGuilhian Leipnitz

Abstract

Sulfite oxidase (SOX) deficiency is an inherited neurometabolic disorder biochemically characterized by tissue accumulation and high urinary excretion of sulfite and thiosulfate. Affected patients present severe neurological dysfunction accompanied by seizures, whose pathophysiology is poorly known. In the present study we evaluated the in vitro effects of sulfite and thiosulfate on important parameters of glutamatergic neurotransmission and redox homeostasis in rat cerebral cortex slices. We verified that sulfite, but not thiosulfate, significantly decreased glutamate uptake when cerebral cortex slices were exposed during 1h to these metabolites. We also observed that thiosulfate inhibited glutamine synthetase (GS) activity. A pronounced trend toward GS inhibition induced by sulfite was also found. Regarding redox homeostasis, sulfite, at the concentration of 10 μM, increased thiobarbituric acid-reactive substances and decreased glutathione concentrations after 1h of exposure. In contrast, thiosulfate did not alter these parameters. We also found that 500 μM sulfite increased sulfhydryl group content in rat cerebral cortex slices and increased GSH levels in a medium containing oxidized GSH (GSSG) and devoid of cortical slices,...Continue Reading

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Citations

Apr 8, 2016·Current Opinion in Chemical Biology·Guenter Schwarz
Aug 16, 2016·Biochimica Et Biophysica Acta·Mateus GringsGuilhian Leipnitz
Nov 13, 2019·Reviews in the Neurosciences·Thomas BerryAhmed A Moustafa
Nov 22, 2019·Reviews in the Neurosciences·Thomas BerryAhmed A Moustafa
Jul 30, 2018·Neurotoxicity Research·Mateus GringsGuilhian Leipnitz
Apr 19, 2017·Neurotoxicity Research·Leonardo de Moura AlvorcemGuilhian Leipnitz

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