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PubMed1989

Site-specific DNA damage induced by sulfite in the presence of cobalt(II) ion. Role of sulfate radical.

The reactivities of sulfite (SO23-) with DNA in the presence of metal ions were investigated by a DNA sequencing technique using 32P-labeled DNA fragments obtained from human c-Ha-ras-1 protooncogene. Sulfite caused DNA damage in the presence of Co2+, Cu2+ and Mn2+, although sulfite alone or metal ion alone did not. The order of inducing effect on sulfite-dependent DNA damage (Co2+ much greater than Cu2+ greater than Mn2+ Fe3+) was consistent with that of accelerating effect on the initial oxygen consumption rate of sulfite autoxidation. The DNA damage induced by sulfite plus Co2+ was inhibited by 3,5-dibromo-4-nitrobenzenesulfonate, primary and secondary alchols, whereas it was not inhibited by SOD, catalase and tert-butyl alcohol. Incubation of DNA with sulfite plus Co2+ followed by the piperidine treatment led to the predominant cleavage at the positions of guanine especially located 5' to guanine. Sulfite plus Cu2+ gave a DNA cleavage pattern different from that induced by sulfite plus Co2+. The photolysis of peroxydisulfate (S2O28-), which is known to produce SO-4 radicals, gave a DNA cleavage pattern similar to that induced by sulfite plus Co2+. ESR studies using spin-trapping reagent revealed the production of spin adduct possibly of SO-3 radical in a solution of sulfite plus Cu2+, whereas much less spin adduct was produced by sulfite plus Co2+. The results suggest that sulfite is rapidly autoxidized in the presence of Co2+ to produce SO4- radical causing site-specific DNA damage.

Alcohols↗

PubMed2005

A new type of sulfite reductase, a novel coenzyme F420-dependent enzyme, from the methanarchaeon Methanocaldococcus jannaschii.

Methanocaldococcus jannaschii is a hypertheromphilic, strictly hydrogenotrophic, methanogenic archaeon of ancient lineage isolated from a deep-sea hydrothermal vent. It requires sulfide for growth. Sulfite is inhibitory to the methanogens. Yet, we observed that M. jannaschii grows and produces methane with sulfite as the sole sulfur source. We found that in this organism sulfite induces a novel, highly active, coenzyme F(420)-dependent sulfite reductase (Fsr) with a cell extract specific activity of 0.57 mumol sulfite reduced min(-1) mg(-1) protein. The cellular level of Fsr protein is comparable to that of methyl-coenzyme M reductase, an enzyme essential for methanogenesis and a possible target for sulfite. Purified Fsr reduces sulfite to sulfide using reduced F(420) (H(2)F(420)) as the electron source (K(m): sulfite, 12 microm; H(2)F(420), 21 microm). Therefore, Fsr provides M. jannaschii an anabolic ability and protection from sulfite toxicity. The N-terminal half of the 70-kDa Fsr polypeptide represents a H(2)F(420) dehydrogenase and the C-terminal half a dissimilatory-type siroheme sulfite reductase, and Fsr catalyzes the corresponding partial reactions. Previously described sulfite reductases use nicotinamides and cytochromes as electron carriers. Therefore, this is the first report of a coenzyme F(420)-dependent sulfite reductase. Fsr homologs were found only in Methanopyrus kandleri and Methanothermobacter thermautotrophicus, two strictly hydrogenotrophic thermophilic methanogens. fsr is the likely ancestor of H(2)F(420) dehydrogenases, which serve as electron input units for membrane-based energy transduction systems of certain late evolving archaea, and dissimilatory sulfite reductases of bacteria and archaea. fsr could also have arisen from lateral gene transfer and gene fusion events.

Amino Acid Sequence↗

PubMed1996

Enhancement of benzo[a]pyrene diol epoxide mutagenicity by sulfite in a mammalian test system.

Sulfur dioxide, a ubiquitous air pollutant, is a co-carcinogen for benzo[a]pyrene (BP). We have demonstrated previously that the interaction between sulfite, the physiological form of sulfur dioxide, and (+/-) -7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE), the ultimate carcinogenic form of BP, results in an enhanced mutagenic effect in Salmonella typhimurium strains TA98 and TA100. We report here that this same co-mutagenic effect of sulfite occurs in a mammalian cell line. Treatment of Chinese hamster V79 cells with 50 nM anti-BPDE, a concentration on the linear portion of the dose-response, resulted in a four-fold increase in mutations at the hprt locus relative to the spontaneous rate. When V79 cells were exposed to 1 or 10 mM sulfite immediately prior to the addition of anti-BPDE, the mutation rate increased by 73% and 210%, respectively, over that elicited by anti-BPDE alone. Sulfite itself was moderately cytotoxic, but caused no increase in mutation over the spontaneous rate. Characterization of the dose- and time-dependance of this enhancement of diol epoxide mutagenicity by sulfite closely resembled the effects seen previously in the bacterial system. In particular, enhancement by sulfite was evident when sulfite was added to the cells between 60 min and 1 min prior to the addition of the diol epoxide. Concurrent addition of sulfite and the diol epoxide attenuated the enhancement, and the effect was lost altogether when sulfite was added 10 min after the diol epoxide. The specificity of this effect of sulfite was shown by comparison with sulfate, which at concentrations of either 1 or 10 mM exhibited modest cytotoxicity, but neither was directly mutagenic nor able to enhance the mutagenic effect of anti-BPDE. Binding studies with labeled anti-BPDE showed that the addition of 10 mM sulfite increased binding of anti-BPDE to DNA by over 43%, corresponding to the observed increase in mutant frequency. Interestingly, this difference in level of DNA modification was not apparent after 30 min to 2 h exposures, but only emerged at the 4 h time point. The 4 h point was routinely used for all mutagenicity studies. Binding of anti-BPDE-derived materials to cellular RNA was not altered by 10 mM sulfite. The emergence of increased DNA modification at the latest time point suggests either a more prolonged period of active DNA binding than would occur with diol epoxide, or a difference in the ability to recognize and clear specific DNA adducts. Both possibilities are discussed in regard to the observed formation of 7r,8t,9t-trihydroxy-7,8,9,10-tetrahydrobenzo[a] pyrene-10c-sulfonate (BPT-10-sulfonate) in those incubations. BPT-10-sulfonate is a relatively stable BP derivative which retains the ability to covalently modify DNA. The role of this derivative in the enhancement of diol epoxide mutagenicity by sulfite is strongly suggested by these data.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed2004

Increased levels of serum sulfite in patients with acute pneumonia.

Sulfite, a common air pollutant, is toxic for humans, causing hypersensitivity or chronic airway diseases. We previously reported that sulfite is actively produced from neutrophils by stimulation with bacterial endotoxin, lipopolysaccharide (LPS). We also found that the serum sulfite concentration is increased in a rat model of sepsis induced by systemic injection of LPS. However, information on sulfite metabolism in human inflammatory conditions is limited. In the current study, the serum concentration of sulfite was determined in 25 patients with acute pneumonia. Serum sulfite concentration in pneumonia patients was significantly higher than that in control subjects (3.75 +/- 0.88 vs. 1.23 +/- 0.48 microM, respectively, P < 0.05). Among 20 patients, serum sulfite was serially determined before and after antibiotic therapy. The levels of serum sulfite were significantly reduced during the recovery phase compared with those during the acute phase (1.34 +/- 0.56 vs. 3.65 +/- 0.92 microM, respectively, P < 0.05). Moreover, neutrophils obtained from three patients during the acute phase of pneumonia spontaneously produced higher amounts of sulfite in vitro than those obtained after recovery. There was a close positive correlation (r = 0.71, P < 0.05) between serum sulfite and C-reactive protein (CRP) in patients with pneumonia. Taken together, the current findings suggest that serum sulfite increases during systemic inflammation in humans. Activated neutrophils might be responsible, at least in part, for the up-regulation of sulfite. Given various biological effects reported previously, sulfite may act as a mediator in inflammation.

Acute Disease↗

PubMed2005

Oxidative stress-dependent conversion of hydrogen sulfide to sulfite by activated neutrophils.

Sulfite, which is known as a major constituent of volcanic gas, is endogenously produced in mammals, and its concentration in serum is increased in patients with pneumonia. It has been reported that sulfite is produced by oxidation from hydrogen sulfide (H2S) as an intermediate in the mammalian body. The objective of this study was to investigate the ability of reactive oxygen species from neutrophils to produce sulfite from H2S. Sulfite production from activated neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine gradually increased with an increased concentration of sodium hydrosulfide (NaHS) in the medium. The production of sulfite was markedly suppressed with an NADPH oxidase inhibitor, diphenyleneiodonium. When NaHS was added to the supernatant of activated neutrophils, a significant amount of sulfite was synthesized in the test tubes. Furthermore, when a medium containing NaHS was incubated with a water-soluble radical initiator, 2,2'-azobis-(amidinopropane) dihydrochloride, sulfite was formed in the solution and this increase was markedly suppressed by ascorbic acid. Finally, we determined serum concentrations of sulfite and H2S in an in vivo model of neutrophil activation induced by systemic injection of lipopolysaccharide (LPS) into rats. We found a significant increase in serum sulfite and H2S after LPS injection. Importantly, coadministration of ascorbic acid with LPS further increased serum H2S but suppressed sulfite levels. This finding implies that oxidative stress-dependent conversion of H2S to sulfite might occur in vivo. Thus, the oxidation of H2S is a novel sulfite production pathway in the inflammatory condition, and this chemical synthesis might be responsible for the upregulation of sulfite production in inflammatory conditions such as pneumonia.

Animals↗

PubMed2006

Effect of sulfite exposure on zinc, iron, and copper levels in rat liver and kidney tissues.

Sulfite is a potentially toxic molecule that might enter the body via ingestion, inhalation, or injection. For cellular detoxification, mammalians rely on sulfite oxidase to convert sulfite to sulfate. The purpose of this research was to determine the effect of sulfite on zinc, iron, and copper levels in rat liver and kidney tissues. Forty normal and sulfite oxidase-deficient male albino rats were divided into four groups that included untreated controls (group C), a sulfite-supplemented group that received 70 mg sodium metabisulfite per kilogram per day (group S), a sulfite oxidase-deficient group (group D), and a sulfite oxidase-deficient group that was also given 70 mg sodium metabisulfite per kilogram per day (group DS). The iron and zinc levels in the liver and kidney in groups S and DS were not affected by sulfite treatment compared to their respective controls (groups C and D). Sulfite exposure led to an increase of kidney copper content in the S group when compared to untreated controls. The kidney copper levels were significantly increased in the unexposed deficient rats, but it was not different than that of the deficient rats that were given oral sulfite treatment. These results suggest that kidney copper levels might be affected by exogenous or endogenous sulfite.

Animals↗

PubMed2005

Novel homogeneous catalyst system for the oxidation of concentrated ammonium sulfite.

A homogeneous catalyst system made up of [Co(NH3)6]2+/I- has been put forward to catalyze the oxidation of concentrated ammonium sulfite. The experiments were performed in a packed column with sulfite concentrations above 2.5 mol l(-1), temperature range 20-65 degrees C, and oxygen partial pressure 0.052-0.21 atm. The experimental results indicate that the Co(NH3)6(2+)/I- homogeneous catalyst system can obviously accelerate the concentrated ammonium sulfite oxidation rate. After 2h reaction, the sulfite conversion is only 12.5% with no catalysts while 72.1% sulfite conversion can be obtained with 0.02 mol l(-1) Co(NH3)6(2+) and 0.005 mol l(-1) I- in the ammonium sulfite solution. The sulfite oxidation rate increases 284% as Co(NH3)6(2+) concentration increases from 0.01 to 0.02 mol l(-1). But there is little use increasing the Co(NH3)6(2+) concentration above 0.04 mol l(-1). The sulfite oxidation rate may increase 229% as the temperature increases from 20 to 65 degrees C. Sulfite oxidation rate is independent of the initial sulfite concentration. Increasing the oxygen partial pressure can increase the sulfite conversion. The reaction order with respect to oxygen is 1.2 and sulfite is zero. The apparent activation energy determined is 23.5 kJ mol(-1).

Air Pollutants, Occupational↗

PubMed2004

Sulfites--a food and drug administration review of recalls and reported adverse events.

Sulfite-sensitive individuals can experience adverse reactions after consuming foods containing sulfiting agents (sulfites), and some of these reactions may be severe. In the 1980s and 1990s, the U.S. Food and Drug Administration (FDA) acted to reduce the likelihood that sulfite-sensitive individuals would unknowingly consume foods containing sulfites. The FDA prohibited the use of sulfites on fruits and vegetables (except potatoes) to be served or presented fresh to the public and required that the presence of detectable levels of sulfites be declared on food labels, even when these sulfites are used as a processing aid or are a component of another ingredient in the food. In the present study, data from FDA recall records and adverse event reports were used to examine the current status of problems of sensitivity to sulfites in foods. From 1996 through 1999, the FDA processed a total of 59 recalls of foods containing undeclared sulfites; these 59 recalls involved 93 different food products. Fifty (55%) of the recalled products were classified as class I, a designation indicating that a consumer reasonably could have ingested > or = 10 mg of undeclared sulfites on a single occasion, a level that could potentially cause a serious adverse reaction in a susceptible person. From 1996 through mid-1999, the FDA received a total of 34 reports of adverse reactions allegedly due to eating foods containing undeclared sulfites. The average of 10 reports per year, although derived from a passive surveillance system, was lower than the average of 111 reports per year that the FDA received from 1980 to 1987, a decrease that may have resulted in part from FDA regulatory action.

Allergens↗

PubMed1982

Sulfite-induced lipid peroxidation in chloroplasts as determined by ethane production.

Ethane formation, as a measure of lipid peroxidation, was studied in spinach (Spinacia oleracea L.) chloroplasts exposed to sulfite. Ethane formation required sulfite and light, and occurred with concomitant oxidation of sulfite to sulfate. In the dark, both ethane formation and sulfite oxidation were inhibited. Ethane formation was stimulated by ferric or ferrous ions and inhibited by ethylenediamine tetraacetate. The photosynthetic electron transport modulators, 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) and phenazine methosulfate, inhibited both sulfite oxidation and ethane formation. Methyl viologen greatly stimulated ethane formation, but had little effect on sulfite oxidation. Methyl viologen, in the absence of sulfite, caused only a small amount of ethane formation in comparison to that produced with sulfite alone. Sulfite oxidation and ethane formation were effectively inhibited by the radical scavengers, 1,2-dihydroxybenzene-3,5-disulfonic acid and ascorbate. Ethanol, a hydroxyl radical scavenger, inhibited ethane formation only to a small degree; formate, which converts hydroxyl radical to superoxide radical, caused a small stimulation in both sulfite oxidation and ethane formation. Superoxide dismutase inhibited ethane formation by 50% when added at a concentration equivalent to that of the endogenous activity. Singlet oxygen did not appear to play a role in ethane formation, inasmuch as the singlet oxygen scavengers, sodium azide and 1,4-diazobicyclo-[2,2,2]-octane, were not inhibitory. These data are consistent with the view that O(2) is reduced by the photosynthetic electron transport system to superoxide anion, which in turn initiates the free radical oxidation of sulfite, and the free radicals produced during sulfite oxidation were responsible for the peroxidation of membrane lipids, resulting in the formation of ethane.

Journal Article↗

PubMed1994

Responses of human neutrophils to sulfite.

Exposure to sulfur dioxide or sulfite aerosols induce inflammatory reactions in the respiratory tract characterized by an influx of neutrophils into the airways. To determine direct intracellular effects of sulfite on human neutrophils, these cells were evaluated ultrastructurally by electron microscopy and analyzed for their extracellular and intracellular respiratory burst activity after incubation with sulfite (0.01-10 mM) in vitro. The respiratory burst was quantitated by measuring both the extracellular release of superoxide anions (O2-) by superoxide dismutase-inhibitable lucigenin-dependent chemiluminescence (CL) and the intracellular generation of hydrogen peroxide (H2O2) by flow cytometry using the reagent dichlorofluorescein diacetate. The addition of sulfite in concentrations of 0.01-1 mM resulted in sixfold increases in CL of resting neutrophils. Neutrophils stimulated with zymosan, phorbol myristate acetate (PMA), or N-formyl-methionine-leucine-phenylalanine further increased CL when sulfite was added. Higher sulfite concentrations (2-10 mM) decreased CL of resting, zymosan-stimulated, and PMA-stimulated cells. When sulfate was added, no changes in CL of resting and zymosan-stimulated neutrophils were seen, indicating that the effect is specific for sulfite. The intracellular generation of H2O2 in resting and PMA-stimulated neutrophils incubated with sulfite (0.1-2 mM) was increased twofold. These findings suggest that sulfite in low concentrations stimulates neutrophils by activating the respiratory burst to produce O2- and H2O2. Ultrastructural studies confirm the stimulating effect of sulfite on neutrophils with sulfite-treated cells exhibiting increased ruffled surface membranes, degranulation changes, and vesiculation similar to those seen in PMA-stimulated cells.

Humans↗

PubMed2002

Sulfite supported lipid peroxidation in propofol emulsions.

BACKGROUND: Sodium metabisulfite is added to a commercial propofol emulsion as an antimicrobial agent. The sulfite ion (SO3(-2)) is capable of undergoing a number of reactions, including autooxidation and the promotion of lipid peroxidation. This study evaluated sulfite reactivity in propofol emulsions by determining thiobarbituric acid reacting substances (TBARS), sulfite depletion, and emulsion pH in emulsions containing sulfite or EDTA. METHODS: Commercial EDTA and sulfite propofol emulsions were compared, and 10% soybean oil emulsion containing various additives were evaluated for TBARS, sulfite, and pH. TBARS were analyzed with a modified thiobarbituric acid method. Sulfite was analyzed by the reaction of sulfite with 5,5'-dithiobis(2-nitrobenzoic acid). pH was measured by glass electrode methodology. RESULTS: Thiobarbituric acid reacting substances were detectable in commercial sulfite propofol emulsions in concentrations ranging from 0.02 to 0.22 microg/ml based on malondialdehyde. No TBARS were detected in EDTA propofol emulsions. Incubation (37 degrees C, up to 6 h) of sulfite propofol emulsions in air resulted in further increases in TBARS (35-160%). No increases occurred in incubated EDTA propofol emulsions. Metabisulfite (0.25 mg/ml) alone added to 10% soybean oil resulted in large increases in TBARS that were inhibited in part by propofol (10 mg/ml) and completely by ascorbic acid (0.05 mg/ml). Soybean oil emulsion pH declined rapidly on the addition of metabisulfite (0.25 mg/ml). The addition of propofol (10 mg/ml) partially inhibited the decline in pH and ascorbic acid (0.05 mg/ml) completely inhibited it. CONCLUSION: These results show that sulfite supports the peroxidation of lipids in soybean oil emulsions and propofol functions to partially inhibit these processes.

Ascorbic Acid↗

PubMed2004

Role of lipid in sulfite-dependent propofol dimerization.

BACKGROUND: During long-term intravenous infusions, sulfite in sulfite-containing propofol emulsions can cause the peroxidation of lipid and dimerization of propofol. This study evaluated the role of lipid in sulfite-dependent propofol dimerization by determining the effects of individual fatty acids in soybean oil emulsion and peroxidized lipids in a model system. METHODS: Individual fatty acids, stearic (18:0), oleic (18:1), linoleic (18:2), linolenic (18:3), and arachidonic (20:4), were added to sulfite-containing propofol emulsion and incubated for 90 min at 37 degrees C. Model systems containing soybean oil (100 microl), water (900 microl), propofol (10 mg/ml), and sulfite (0.25 mg/ml) composed of oils with different peroxide values were allowed to react for 60 min at room temperature. After the reactions, propofol dimer and propofol dimer quinone were analyzed by reversed-phase high-pressure liquid chromatography. RESULTS: Propofol did not dimerize when added to aqueous sulfite unless soybean oil was also included. The addition of the polyunsaturated fatty acids (linoleic, linolenic, arachidonic) to sulfite-containing propofol emulsion resulted in large increases of propofol dimerization compared with stearic or oleic acid. Using biphasic mixtures of soybean oil and aqueous sulfite, propofol dimerization increased with increasing peroxide content of the oil. In propofol emulsion, lipoxidase and ferrous iron in the absence of sulfite also caused the dimerization of propofol. CONCLUSIONS: These results show that lipid can play a significant role in sulfite-dependent propofol dimerization. The relation of dimerization to polyunsaturated fatty acid and soybean oil peroxide content suggests that sulfite reacts with unsaturated lipid or peroxide-modified lipid to facilitate propofol dimerization.

Dimerization↗

PubMed2003

Free radical and drug oxidation products in an intensive care unit sedative: propofol with sulfite.

OBJECTIVES: Some propofol emulsion formulations contain EDTA or sodium metabisulfite to inhibit microbe growth on extrinsic contamination. EDTA is not known to react with propofol formulation components; however, sulfite has been shown to support some oxidation processes and may react with propofol. This study compared the oxidation of propofol and the formation of free radicals by electron paramagnetic resonance analysis in EDTA and sulfite propofol emulsions during a simulated intensive care unit 12-hr intravenous infusion. DESIGN: Controlled laboratory study. SETTING: University laboratory. MEASUREMENTS AND MAIN RESULTS: Propofol emulsions (3.5 mL) were dripped from spiked 50-mL vials at each hour for 12 hrs. Two propofol oxidation products, identified as propofol dimer and propofol dimer quinone, were detected in sulfite and EDTA propofol emulsions; however, sulfite propofol emulsion contained higher quantities of both compounds. After initiation of the simulated infusion, the quantities of propofol dimer and propofol dimer quinone increased in the sulfite propofol emulsion, but the lower levels in the EDTA propofol emulsion remained constant. Sulfite propofol emulsion began to visibly yellow at about 6-7 hrs. The EDTA propofol emulsion remained white at all times. The absorbance spectra of the propofol dimer and propofol dimer quinone extracted from sulfite propofol emulsion showed that propofol dimer did not absorb in the visible spectrum, but the propofol dimer quinone had an absorbance peak at 421 nm, causing it to appear yellow. Electron paramagnetic resonance analysis of the propofol emulsion containing metabisulfite revealed that the sulfite propofol emulsion yielded a strong free radical signal consistent with the formation of the sulfite anion radical (SO3*-). The EDTA propofol emulsion yielded no free radical signal above background. CONCLUSION: Sulfite from the metabisulfite additive in propofol emulsion creates an oxidative environment when these emulsions are exposed to air during a simulated intravenous infusion. This oxidation results in propofol dimerization and emulsion yellowing, the latter of which is caused by the formation of propofol dimer quinone. These processes can be attributed to the rapid formation of the reactive sulfite free radical.

Chemistry, Pharmaceutical↗

PubMed1987

Sulfite hypersensitivity. A critical review.

Sulfiting agents (sulfur dioxide and the sodium and potassium salts of bisulfite, sulfite, and metabisulfite) are widely used as preservatives in foods, beverages, and pharmaceuticals. Within the past 5 years, there have been numerous reports of adverse reactions to sulfiting agents. This review presents a comprehensive compilation and discussion of reports describing reactions to ingested, inhaled, and parenterally administered sulfite. Sulfite hypersensitivity is usually, but not exclusively, found within the chronic asthmatic population. Although there is some disagreement on its prevalence, a number of studies have indicated that 5 to 10% of all chronic asthmatics are sulfite hypersensitive. This review also describes respiratory sulfur dioxide sensitivity which essentially all asthmatics experience. Possible mechanisms of sulfite hypersensitivity and sulfur dioxide sensitivity are discussed in detail. Sulfite metabolism and the role of sulfite oxidase in the detoxification of exogenous sulfite are reviewed in relationship to the etiology of sulfite hypersensitivity.

Administration, Oral↗

PubMed1998

Sulfite is released by human neutrophils in response to stimulation with lipopolysaccharide.

Exposure to sulfite, a well-known air pollutant, induces inflammatory reactions characterized by neutrophil infiltration into the airways. Using a simple and sensitive assay for sulfite concentration in biological fluids, we demonstrate herein that human neutrophils released significant amounts of sulfite (1.0 nmol/h/10(7) cells) in response to lipopolysaccharide (LPS), a major component of bacterial endotoxin. A large proportion of the sulfite release by neutrophils was dependent on inorganic sulfate contained in culture media, suggesting production via the sulfate reducing pathway in this response. We also show that glucocorticoids and FK506 completely inhibit LPS-mediated sulfite release by neutrophils. Given the well-known antimicrobial activities of sulfite, our results suggest that sulfite acts as a neutrophil mediator of host defense. A putative role of sulfite as an endogenous biological mediator is further underscored by the observation that in vivo administration of LPS is associated with a marked increase in the serum concentration of sulfite in Wistar rats. Inhibition of sulfite release by immunosuppressive agents may contribute to increased susceptibility to bacterial infection commonly associated with the administration of these drugs.

Animals↗

PubMed1991

Inhibition of browning by sulfites.

The present state of understanding of the mechanisms by which sulfites inhibit browning reactions in food is reviewed. The difficulties of specifying the composition of sulfur(IV) oxospecies in sulfited foods arise from the existence of labile equilibria between SO2, HSO3-, SO3(2-) and S2O5(2-), whose position depends on concentration, ionic strength and the presence of non-electrolytes. A proportion of the additive is also found in a reversibly bound form. The main reason why sulfites are able to inhibit a wide range of browning reactions is the nucleophilic reactivity of sulfite ion. The mechanism of reactions between sulfite species and intermediates in the model Maillard browning reaction, glucose + glycine, are considered in depth and are supported by kinetic data. A most interesting feature is the fact that sulfites seem to catalyse the reactions they are added to control. Reaction products include 3,4-dideoxy-4-sulfohexosulose which is formed initially and polymeric substances arise from the reaction of sulfite species with melanoidins. It is found that melanoidins from glucose + glycine react with sulfite to such an extent that one sulfur atom is incorporated for every two glucose molecules used to make up the polymer. The mechanisms of inhibition of ascorbic acid browning, enzymic browning and lipid browning are reviewed briefly. The known toxicological consequences of the formation of reaction products when sulfites are used for the control of Maillard browning give little cause for concern. Little is known of the implications of the formation of reaction products during the inhibition of other forms of browning. Consideration of the requirements for alternatives to sulfites is given.

Maillard Reaction↗

PubMed2004

A mechanism of sulfite neurotoxicity: direct inhibition of glutamate dehydrogenase.

Exposure of Neuro-2a and PC12 cells to micromolar concentrations of sulfite caused an increase in reactive oxygen species and a decrease in ATP. Likewise, the biosynthesis of ATP in intact rat brain mitochondria from the oxidation of glutamate was inhibited by micromolar sulfite. Glutamate-driven respiration increased the mitochondrial membrane potential (MMP), and this was abolished by sulfite but the MMP generated by oxidation of malate and succinate was not affected. The increased rate of production of NADH from exogenous NAD+ and glutamate added to rat brain mitochondrial extracts was inhibited by sulfite, and mitochondria preincubated with sulfite failed to reduce NAD+. Glutamate dehydrogenase (GDH) in rat brain mitochondrial extract was inhibited dose-dependently by sulfite as was the activity of a purified enzyme. An increase in the Km (glutamate) and a decrease in Vmax resulting in an attenuation in Vmax/Km (glutamate) at 100 microm sulfite suggest a mixed type of inhibition. However, uncompetitive inhibition was noted with decreases in both Km (NAD+) and Vmax, whereas Vmax/Km (NAD+) remained relatively constant. We propose that GDH is one target of action of sulfite, leading to a decrease in alpha-ketoglutarate and a diminished flux through the tricarboxylic acid cycle accompanied by a decrease in NADH through the mitochondrial electron transport chain, a decreased MMP, and a decrease in ATP synthesis. Because glutamate is a major metabolite in the brain, inhibition of GDH by sulfite could contribute to the severe phenotype of sulfite oxidase deficiency in human infants.

Adenosine Triphosphate↗

PubMed1997

Sulfite stimulates the ATP hydrolysis activity of but not proton translocation by the ATP synthase of Rhodobacter capsulatus and interferes with its activation by delta muH+.

Sulfite stimulates the rate of ATP hydrolysis by the ATP synthase in chromatophores of Rhodobacter capsulatus. The stimulated activity is inhibited by oligomycin. The activation takes place also in uncoupled chromatophores. The activation consists in an increase of about 12-15-fold of the Vmax for the ATP hydrolysis reaction, while the Km for MgATP is unaffected at 0.16+/-0.03 mM. The dependence of Vmax on the sulfite concentration follows a hyperbolic pattern with half maximum effect at 12 mM. Sulfite affects the ability of the enzyme in translocating protons. Concomitant measurements of the rate of ATP hydrolysis and of ATP-induced protonic flows demonstrate that at sulfite concentrations of greater than 10 mM the hydrolytic reaction becomes progressively uncoupled from the process of proton translocation. This is accompanied by an inhibition of ATP synthesis, either driven by light or by artificially induced ionic gradients. ATP synthesis is totally inhibited at concentrations of at least 80 mM. Sulfite interferes with the mechanism of activation by delta muH+. Low concentrations of this anion (< or = 2 mM) prevent the activation by delta muH+. At higher concentrations a marked stimulation of the activity prevails, regardless of the occurrence of a delta muH+ across the membrane. Phosphate at millimolar concentrations can reverse the inhibition by sulfite. These experimental results can be simulated by a model assuming multiple and competitive equilibria for phosphate or sulfite binding with two binding sites for the two ligands (for sulfite K1S = 0.26 and K2S = 37 mM, and for phosphate K1P = 0.06 and K2P = 4.22 mM), and in which the state bound only to one sulfite molecule is totally inactive in hydrolysis. The competition between phosphate and sulfite is consistent with the molecular structures of the two ligands and of the enzyme.

Adenosine Triphosphate↗