TOXIC EFFECTS OF SULFITE IN COMBINATION WITH PEROXYNITRITE ON NEURONAL CELLS

Sulphite is widely used as a preservative and antioxidant in foods, be verages, and pharmaceuticals. Endogenous sulphite is generated during the normal metabolism of sulphur-containing amino acids, and alteratio ns in sulphur amino acid metabolism occur in some neurodegenerative di seases. In particular, sulphite oxidase deficiency produces severe men tal retardation, seizures, spastic quadriparesis, dislocated lenses, a nd early death. Exposure of a neuronal cell line(rat mesencephalic cel ls) to high levels of sulphite induced a time-dependent decrease in vi ability. Peroxynitrite was also toxic to this cell line, and sulphite affected the toxicity of ONOO-. Sulphite concentrations of less than o r equal to 0.5 mM markedly potentiated cell damage induced by 200 mu M ONOO-. We propose that sulphite can act as a neurotoxic agent, especi ally in combination with peroxynitrite. Sulphite radicals may be invol ved in the neurotoxic effect.