Dose-dependent effect of nutritional sulfite intake on visual evoked potentials and lipid peroxidation Nihal Ozturk a , Piraye Yargicoglu a, ⁎, Narin Derin a , Deniz Akpinar a , Aysel Agar b , Mutay Aslan c a Akdeniz University, Faculty of Medicine, Department of Biophysics, Turkey b Akdeniz University, Faculty of Medicine, Department of Physiology, Turkey c Akdeniz University, Faculty of Medicine, Department of Biochemistry, Turkey abstract article info Article history: Received 1 February 2010 Received in revised form 16 September 2010 Accepted 16 September 2010 Available online 25 September 2010 Keywords: Sulfite Visual evoked potentials Lipid peroxidation The aim of this study was to clarify the dose-dependent effect of sulfite (SO 3 2- ) ingestion on brain and retina by means of electrophysiological and biochemical parameters. Fifty two male Wistar rats, aged 3 months, were randomized into four experimental groups of 13 rats as follows; control (C), sulfite treated groups (S 1 ; 10 mg/kg/ day, S 2 ; 100 mg/kg/day, S 3 ; 260 mg/kg/day). Control rats were administered distilled water, while the other three groups were given sodium metabisulfite (Na 2 S 2 O 5 ) of amounts mentioned above, via gavage for a period of 35 days. All components of visual evoked potential (VEP) were prolonged in S 2 and S 3 groups compared with S 1 and C groups. Plasma-S-sulfonate levels, which are an indicator of sulfur dioxide (SO 2 ) exposure, were increased in Na 2 S 2 O 5 treated groups in a dose-dependent manner. Furthermore, the significant increments in thiobarbituric acid reactive substances (TBARS) and 4-hydroxy-2-nonenal (4-HNE) levels occurred with increasing intake of Na 2 S 2 O 5 . Though not significant, glutathione (GSH) and oxidized glutathione (GSSG) levels were observed to decrease with increasing doses of Na 2 S 2 O 5 . In conclusion, Na 2 S 2 O 5 treatment in rats caused a dose-dependent increase in lipid peroxidation and all VEP latencies. The data indicate that lipid peroxidation could play an important role in sulfite toxicity. © 2010 Elsevier Inc. All rights reserved. 1. Introduction Humans are exposed to both endogenous and exogenous sulfites. The most common exogenous source is sulfiting agents that are widely used as preservatives in foods, beverages and drugs (Gunnison and Jacobsen, 1987) for a variety of important technical purposes, including the control of enzymatic and non-enzymatic browning and antimicrobial actions (Taylor et al., 1986). Considerable amount of sulfites is also generated endogenously by the metabolism of sulfur- containing amino acids (Cooper, 1983; Taylor et al., 1986). Once ingested, sulfite salts react with water leading to the generation of bisulfite (HSO 3 - ), sulfite (SO 3 2- ) and sulfur dioxide (SO 2 )(Gunnison and Jacobsen, 1987). Thus, the amounts of ingested sulfites are expressed as sulfur dioxide equivalents (SDE). Previous studies have shown that ingested sulfite enters into the systemic circulation by gastrointestinal absorption and distributed essentially to all body tissues including the brain (Gunnison and Benton, 1988; Gunnison and Jacobsen, 1987). Both endogenously generated and exogenous intake of sulfite must be detoxified because it can react with a variety of humoral and cellular components and can cause toxicity. It is well known that mammalian tissues contain the enzyme sulfite oxidase, which catalyzes the oxidative detoxification of sulfite. If there is deficiency of sulfite oxidase or exposure to excessive sulfite, the sulfite under- goes one electron oxidation reactions which is catalyzed by peroxidases (Mottley and Mason, 1988). It is suggested that sulfite- induced toxicity may involve the formation of sulfur- and oxygen- centered free radicals (Shi and Mao, 1994). Since the central neuronal system is highly sensitive to free radicals, it is postulated that sulfite- induced neurotoxicity may be associated with oxidation of lipids, proteins and nucleic acids generated via free radicals. In addition, sulfite also reacts with disulfide bonds to form S-sulfonates by a process termed sulfitolysis. Disulfide bonds can occur in low molecular weight compounds e.g. cystine and oxidized glutathione (GSSG) or macromolecules such as proteins (Gunnison and Jacobsen, 1987). Thus, sulfitolysis of GSSG affects antioxidant defense system and increases susceptibility to oxidative stress. The toxic effects of sulfite on mammals have been studied extensively (Alarie et al., 1970; Atkinson et al., 1993; Gunnison and Benton, 1988; Kodavanti et al., 2000; Samet et al., 2000). Previous studies performed on monkeys and guinea pigs have found no detrimental effect of long-term exposure to SO 2 from 0.1 to 5 ppm Neurotoxicology and Teratology 33 (2011) 244–254 ⁎ Corresponding author. Department of Biophysics, Faculty of Medicine, Akdeniz University, Arapsuyu, 07070 Antalya, Turkey. Tel.: + 90 242 2281959(residence), + 90 242 2276994(work); fax: + 90 242 2274495. E-mail address: pakkiraz@akdeniz.edu.tr (P. Yargicoglu). 0892-0362/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.ntt.2010.09.002 Contents lists available at ScienceDirect Neurotoxicology and Teratology journal homepage: www.elsevier.com/locate/neutera