Spinal reflexes in normal and sulfite oxidase deficient rats: effect of sulfite exposure

Abstract

Sulfites, which are commonly used as food preservatives, are continuously formed in the body during metabolism of sulfur-containing amino acids. Sulfite is oxidized to sulfate ion by sulfite oxidase (SOX, EC. 1.8.3.1). Although sulfite treatment has been reported to increase the excitability of some neurons in vitro, the possible effects of sulfite on neuronal excitability in vivo remain unclear. The aim of this study was to investigate the possible effects of sulfite treatment on spinal reflexes in anesthetized SOX competent and deficient rats. For this purpose, male albino rats used in this study were divided into four groups such as control group (C), sulfite group (CS), SOX deficient group (D), and SOX deficient + sulfite group (DS). Rats in SOX deficient groups were made deficient in SOX by the administration of low molybdenum (Mo) diet (AIN 76, Research Dyets Inc., USA) with concurrent addition of 200-ppm tungsten (W) to their drinking water in the form of sodium tungstate (NaWO₄). Sulfite in the form of sodium metabisulfite (Na₂O₅S₂, 70 mg/kg) was given orally by adding to drinking water to the S and DS groups. Monosynaptic reflex potentials were recorded from the ipsilateral L5 ventral root. SOX deficient rats had an approximately 15-fold decrease in hepatic SOX activity compared with normal rats. This makes SOX activity of SOXD rats in the range of human SOX activity. The results of this study show that sulfite treatment significantly increases the amplitude of the monosynaptic reflex response in both S and DS groups with respect to their respective control groups (C and D). SOX deficient rats also had enhanced spinal reflexes when compared with control rats. In conclusion, sulfite has increasing effects on the excitability of spinal reflexes and we speculate that this compound may exhibit its effects on nervous system by affecting sodium channels.

Keywords

food additives spinal reflexes and rat sulfite

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References

Cabre F Marin C Cascante M Canela EI (1990) Occurrence and comparison of sulfite oxidase activity in mammalian tissues. Biochem Med Metab Biol 43: 159–162.

Cohen HJ Drew RT Johnson JL Rajagopalan KV (1973) Molecular basis of the biological function of molybdenum: the relationship between sulfite oxidase and the acute toxicity of bisulfite and SO2. Proc Natl Acad Sci U S A 70: 3655–3659.

Cohen HJ Fridovich I (1971) Hepatic sulfite oxidase. Purification and properties. J Biol Chem 246: 359–366.

Constantin D Mehrotra K Jernstrom B Tomasi A Moldéus P (1994) Alternative pathways of sulfite oxidation in human polymorphonuclear leukocytes. Pharmacol Toxicol 74: 136–140.

Dalton-Bunnow MF (1985) Review of sulfite sensitivity. Am J Hosp Pharm 42: 2220–2226.

Du Z Meng Z (2004) Modulation of sodium currents in rat dorsal root ganglion neurons by sulfur dioxide derivatives. Brain Res 1010: 127–133.

Dulak L Chiang G Gunnison AF (1984) A sulphite oxidase-deficient rat model: reproductive toxicology of sulphite in the female. Toxicology 22: 599–607.

Elmas O Aslan M Caglar S Derin N Agar A Alicigüzel Y Yargiçoglu P (2005) The prooxidant effect of sodium metabisulfite in rat liver and kidney. Regul Toxicol Pharmacol 42: 77–82.

Food an Agriculture Organization Expert Committee on Food Additives (1974) Toxicological Evaluation of Certain Food Additives with a Review of General Principle and of Specification, 17th report. Rome: FAO/WHO.

10.

Gunnison AF Jacobsen DW (1987) Sulfite hypersensitivity. A critical review. CRC Crit Rev Toxicol 17: 185–214.

11.

Hickey RJ Clelland RC Bowers EJ Boyce DE (1976) Health effects of atmospheric sulfur dioxide and dietary sulfites. The fallacy of typology. Arch Environ Health 31: 108–112.

12.

Johnson L Rajagopalan KV Cohen HJ (1974) Molecular basis of the biological function of molybdenum. Effect of tungsten on xanthine oxidase and sulfite oxidase in the rat. J Biol Chem 249: 859–866.

13.

Kagedal B Kallberg M Sorbo B (1986) A possible involvement of glutathione in the detoxication of sulfite. Biochem Biophys Res Commun 136: 1036–1041.

14.

Kisker C Schindelin H Rees DC (1997) Molybdenum-cofactor-containing enzymes: structure and mechanism. Annu Rev Biochem 66: 233–267.

15.

Kucukatay V Savcioglu F Hacioglu G Yargiçoğlu P Ağar A (2005) Effect of sulfite on cognitive function in normal and sulfite oxidase deficient rats. Neurotoxicol Teratol 27: 47–54.

16.

Lester MR (1995) Sulfite sensitivity: significance in human health. J Am Coll Nutr 14: 229–232.

17.

Lowry OH Rosenbrough NJ Far AL Randall RJ (1951) Protein measurement with folin-phenol reagent. J Biol Chem 193: 265–275.

18.

Meng ZQ; Sang N; (2002) Effect of SO₂ derivatives on sodium currents in acutely isolated rat hippocampal CA1 neurons. Sheng Li Xue Bao: (Acta physiologica Sinica) 54: 267–270.

19.

Mudd SH Irreverre F Laster L (1967) Sulfite oxidase deficiency in man: demonstration of the enzymatic defect. Science 156: 1599–1602.

20.

Olney JW Misra CH de Gubareff T (1975) Cysteine-S-sulfate: brain damaging metabolite in sulfite oxidase deficiency. J Neuropathol Exp Neurol 34: 167–177.

21.

Reist M Marshall KA Jenner P Halliwell B (1998) Toxic effects of sulphite in combination with peroxynitrite on neuronal cells. J Neurochem 71: 2431–2438.

22.

Shi X Mao Y (1994) 8-Hydroxy-2'-deoxyguanosine formation and DNA damage induced by sulfur trioxide anion radicals. Biochem Biophys Res Commun 205: 141–147.

23.

Simon RA (1986) Sulfite sensitivity. Ann Allergy 56: 281–288.

24.

Southerland WM Akogyeram CO Toghrol F Sloan L Scherrer R (1982) Interaction of bisulfite with unsaturated fatty acids. J Toxicol Environ Health 10: 479–491.

25.

Taylor SL Higley NA Bush RK (1986) Sulfites in foods: uses, analytical methods, residues, fate, exposure assessment, metabolism, toxicity, and hypersensitivity. Adv Food Res 30: 1–76.

26.

Til HP Feron VJ De Groot AP (1972) The toxicity of sulphite. I. Long-term feeding and multigeneration studies in rats. Food Cosmet Toxicol 10: 291–310.

27.

Tortora GJ Grabowski SR (2003) The spinal cord and spinal nerves: Spinal cord physiology. In: Principles of Anatomy and Physiology. editor: Ford, E. New York: John Wiley & Sons, pp. 427–432.

28.

Touati G Rusthoven E Depondt E Dorche C Duran M Heron B Rabier D Russo M Saudubray JM (2000) Dietary therapy in two patients with a mild form of sulphite oxidase deficiency. Evidence for clinical and biological improvement. J Inherit Metab Dis 23: 45–53.

29.

Vincent AS Lim BG Tan J Whiteman M Cheung NS Halliwell B Wong KP (2004) Sulfite-mediated oxidative stress in kidney cells. Kidney Int 65: 393–402.

30.

Wedzicha BL (1992) Chemistry of sulfiting agents in food. Food Addit Contam 9: 449–459.

31.

Woo WH Yang H Wong KP Halliwell B (2003) Sulphite oxidase gene expression in human brain and in other human and rat tissues. Biochem Biophys Res Commun 305: 619–623.