Adverse physiologic effects of a common food additive potassium metabisulfite (E224) in laboratory rats
Corresponding Author
Irfan Zia Qureshi
Laboratory of Animal and Human Physiology, Department of Zoology, Quaid-i-Azam University, Islamabad, Pakistan
Correspondence
Irfan Zia Qureshi, Laboratory of Animal and Human Physiology, Department of Zoology, Quaid-i-Azam University, 45320 Islamabad, Pakistan.
Email: [email protected]
Contribution: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Resources, Supervision, Validation, Writing - review & editing
Search for more papers by this authorNizam Ud Din
Laboratory of Animal and Human Physiology, Department of Zoology, Quaid-i-Azam University, Islamabad, Pakistan
Contribution: Data curation, Formal analysis, Investigation, Methodology
Search for more papers by this authorGhulam Khadija
Laboratory of Animal and Human Physiology, Department of Zoology, Quaid-i-Azam University, Islamabad, Pakistan
Contribution: Formal analysis
Search for more papers by this authorAneeqa Shahzadi
Laboratory of Animal and Human Physiology, Department of Zoology, Quaid-i-Azam University, Islamabad, Pakistan
Contribution: Methodology
Search for more papers by this authorBakhtawer Rafiq
Laboratory of Animal and Human Physiology, Department of Zoology, Quaid-i-Azam University, Islamabad, Pakistan
Contribution: Methodology, Validation
Search for more papers by this authorHina Afaqi
Laboratory of Animal and Human Physiology, Department of Zoology, Quaid-i-Azam University, Islamabad, Pakistan
Contribution: Formal analysis, Methodology, Validation
Search for more papers by this authorCorresponding Author
Irfan Zia Qureshi
Laboratory of Animal and Human Physiology, Department of Zoology, Quaid-i-Azam University, Islamabad, Pakistan
Correspondence
Irfan Zia Qureshi, Laboratory of Animal and Human Physiology, Department of Zoology, Quaid-i-Azam University, 45320 Islamabad, Pakistan.
Email: [email protected]
Contribution: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Resources, Supervision, Validation, Writing - review & editing
Search for more papers by this authorNizam Ud Din
Laboratory of Animal and Human Physiology, Department of Zoology, Quaid-i-Azam University, Islamabad, Pakistan
Contribution: Data curation, Formal analysis, Investigation, Methodology
Search for more papers by this authorGhulam Khadija
Laboratory of Animal and Human Physiology, Department of Zoology, Quaid-i-Azam University, Islamabad, Pakistan
Contribution: Formal analysis
Search for more papers by this authorAneeqa Shahzadi
Laboratory of Animal and Human Physiology, Department of Zoology, Quaid-i-Azam University, Islamabad, Pakistan
Contribution: Methodology
Search for more papers by this authorBakhtawer Rafiq
Laboratory of Animal and Human Physiology, Department of Zoology, Quaid-i-Azam University, Islamabad, Pakistan
Contribution: Methodology, Validation
Search for more papers by this authorHina Afaqi
Laboratory of Animal and Human Physiology, Department of Zoology, Quaid-i-Azam University, Islamabad, Pakistan
Contribution: Formal analysis, Methodology, Validation
Search for more papers by this authorFunding information: This research was conducted through funds already available to the corresponding authors laboratory
Abstract
Current study investigated the effects of potassium metabisulfite (E224), a common food preservative, in male rats following 28 days of oral exposure at doses: 0.7, 7.0, and 70 mg/kg b.w. Following autopsies, blood and tissues samples (liver, kidney, brain, and testes) were taken. Data were compared statistically at p < .05. Potassium metabisulfite caused significant dose-dependent reduction in most hematological parameters except the white blood cells and platelets that showed elevation. Biochemically, dose-dependent significant increase occurred in the oxidative stress biomarkers, the reactive oxygen species, and thiobarbituric acid reactive substances, while a concomitant significant decrease was noticeable in the antioxidant enzymes, superoxide dismutase, peroxidase, catalase, and non-enzymatic reduced glutathione and as well as total protein content in liver, kidneys, brain, and testes of treated animals. Mild to relatively severe histological alterations were noticeable in all tissues. The study for the first time shows that potassium metabisulfite is toxic even in very small quantity.
Novelty impact statement
Potassium metabisulphite designated as E224 is a food preservative used in many food items, but its effects on physiological health are lacking. Rats exposed to its oral doses for 28 continuous days demonstrated that it is toxic even at the lowest recommended concentration of 0.7 mg/kg body weight. It produces excessive free radicals and has every potential to damage the cells biochemically and structurally when used in slightly greater amounts.
CONFLICT OF INTEREST
The authors have declared no conflicts of interest for this article.
Open Research
DATA AVAILABILITY STATEMENT
Data are available and can be submitted on request
REFERENCES
- Adebayo, O. L., & Adenuga, G. A. (2012). Oxidative damage on the testes of adult rats by sodium metabisulfite (MBS). International Journal of Biological and Chemical Sciences, 6(2), 738–744. https://doi.org/10.4314/ijbcs.v6i2.17
10.4314/ijbcs.v6i2.17 Google Scholar
- AL-Sharkawy, A. N., Gab-Allah, M. S., El-Mashad, A. B. I., & Khater, D. F. (2017). Pathological study on the effect of some food additives in male albino rats. Benha Veterinary Medical Journal, 33(2), 75–87.
10.21608/bvmj.2017.29996 Google Scholar
- Aydin, S., Yargicoglu, P., Derin, N., Aliciguzel, Y., Abidin, İ., & Agar, A. (2005). The effect of chronic restraint stress and sulfite on visual evoked potentials (VEPs): Relation to lipid peroxidation. Food and Chemical Toxicology, 43(7), 1093–1101. https://doi.org/10.1016/j.fct.2005.02.014
- Carocho, M., Barreiro, M. F., Morales, P., & Ferreira, I. C. (2014). Adding molecules to food, pros and cons: A review on synthetic and natural food additives. Comprehensive Reviews in Food Science and Food Safety, 13(4), 377–399. https://doi.org/10.1111/1541-4337.12065
- Curti, D., & Benzi, G. (1990). Role of synaptosomal enzymatic alterations and drug treatment in brain aging. Clinical Neuropharmacology, 13, S59–S72. https://doi.org/10.1097/00002826-199013003-00007
- El Kadi, F. Z., Bénali, A. I., Bénali, M., & Belbraouet, S. (2014). Effect of sodium metabisulphite on blood metabolic status of wistar rats. Food and Nutrition Sciences, 5(15), 1529–1537. https://doi.org/10.4236/fns.2014.515165
- Elmas, O., Aslan, M., Çağlar, S., Derin, N., Agar, A., Alıcıgüzel, Y., & Yargıçoğlu, P. (2005). The prooxidant effect of sodium metabisulfite in rat liver and kidney. Regulatory Toxicology and Pharmacology, 42(1), 77–82. https://doi.org/10.1016/j.yrtph.2005.01.010
- Ercan, S., Öztürk, N., Celik-Ozenci, C., Gungor, N. E., & Yargicoglu, P. (2010). Sodium metabisulfite induces lipid peroxidation and apoptosis in rat gastric tissue. Toxicology and Industrial Health, 26(7), 425–431. https://doi.org/10.1177/0748233710369665
- Feng, C., Tollin, G., & Enemark, J. H. (2007). Sulfite oxidizing enzymes. Biochimica Biophysca Acta, 1774(5), 527–539. https://doi.org/10.1016/j.bbapap.2007.03.006
- García-Gavín, J., Parente, J., & Goossens, A. (2012). Allergic contact dermatitis caused by sodium metabisulfite: A challenging allergen. A case series and literature review. Contact Dermatitis, 67(5), 260–269. https://doi.org/10.1111/j.1600-0536.2012.02135.x
- Häberle, M., Geier, J., & Mahler, V. (2017). Contact allergy and intolerance to sulphite compounds: Clinical and occupational relevance. Allergo Journal International, 26(2), 53–66. https://doi.org/10.1007/s40629-016-0003-x
10.1007/s40629-016-0003-x Google Scholar
- Hayashi, I., Morishita, Y., Imai, K., Nakamura, M., Nakachi, K., & Hayashi, T. (2007). High-throughput spectrophotometric assay of reactive oxygen species in serum. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 631(1), 55–61. https://doi.org/10.1016/j.mrgentox.2007.04.006
- Hayes, J. D., & McLellan, L. I. (1999). Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defence against oxidative stress. Free radical research, 31(4), 273–300. https://doi.org/10.1080/10715769900300851
- Gunnison, A. F., Jacobsen, D. W., & Schwartz, H. J. (1987). Sulfite hypersensitivity. A critical review. CRC Critical Reviews in Toxicology, 17(3), 185–214. https://doi.org/10.3109/10408448709071208
- Iqbal, M., Sharma, S. D., Rezazadeh, H., Hasan, N., Abdulla, M., & Athar, M. J. R. R. (1996). Glutathione metabolizing enzymes and oxidative stress in ferric nitrilotriacetate mediated hepatic injury. Redox Report, 2(6), 385–391. https://doi.org/10.1080/13510002.1996.11747079
- Jollow, D. J., Mitchell, J. R., Zampaglione, N., & Gillette, J. R. (1974). Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3, 4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology, 11(3), 151–169. https://doi.org/10.1159/000136485
- Kakkar, P., Das, B., & Viswanathan, P. N. (1984). A modified spectrophotometric assay of superoxide dismutase. Indian Journal of Biochemistry and Biophysics, 21(2), 130–132.
- Küçükatay, V., Savcıoğlu, F., Hacıoğlu, G., Yargıçoğlu, P., & Ağar, A. (2005). Effect of sulfite on cognitive function in normal and sulfite oxidase deficient rats. Neurotoxicology and Teratology, 27(1), 47–54.
- Laggner, H., Hermann, M., Sturm, B., Gmeiner, B. M., & Kapiotis, S. (2005). Sulfite facilitates LDL lipid oxidation by transition metal ions: A pro-oxidant in wine? FEBS Letters, 579(28), 6486–6492. https://doi.org/10.1016/j.febslet.2005.10.045
- Leclercq, C., Le Donne, C., Dr, M. C. F., & Toledo, M. C. F. (2009). Sulfites: Assessment of dietary exposure. WHO Food Addit Ser IPCS—(SAFETY evaluation of certain food additives), 60, 221–244.
- Maehly, A., & Chance, B. (1955). Assay of catalase and peroxidases. Methods in Enzymology, 2(2), 764–775. https://doi.org/10.1016/S0076-6879(55)02300-8
- Mahmoud, A. A. T., Hassan, G. M., Hassan, A. M. S., Latif, A. K. M. A., & Ramadan, M. F. (2015). Demonstrating adverse effects of a common food additive (sodium sulfite) on biochemical, cytological and histopathological parameters in tissues of albino Wister rats. European Journal of Integrative Medicine, 7(3), 234–242. https://doi.org/10.1016/j.eujim.2015.03.003
- Mahmoudi, R., Honarmand, Z., Karbalay-Doust, S., Jafari-Barmak, M., Nikseresht, M., & Noorafshan, A. (2017). Using curcumin to prevent structural impairments of testicles in rats induced by sodium metabisulfite. EXCLI Journal, 16, 583. https://doi.org/10.17179/excli2017-143
- Mamur, S., Yüzbaşıoğlu, D., Ünal, F., & Aksoy, H. (2012). Genotoxicity of food preservative sodium sorbate in human lymphocytes in vitro. Cytotechnology, 64(5), 553–562. https://doi.org/10.1007/s10616-012-9434-5
- Meena, B., Sharma, H., & Sharma, S. (2017). Effects of sub-chronic exposure of the food dye tartrazine on the haematology of swiss albino mice (Mus musculus L.). Indian Journal of Environmental Science, 21(1), 49–52.
- Meng, Z., & Bai, W. (2004). Oxidation damage of sulfur dioxide on testicles of mice. Environmental Research, 96(3), 298–304. https://doi.org/10.1016/j.envres.2004.04.008
- Meng, Z., & Zhang, B. (2003). Oxidative damage of sulfur dioxide inhalation on brains and livers of mice. Environmental Toxicology and Pharmacology, 13(1), 1–8. https://doi.org/10.1016/s1382-6689(02)00106-0
- Meng, Z., & Zhang, L. (1992). Cytogenetic damage induced in human lymphocytes by sodium bisulfite. Mutation Research/Genetic Toxicology, 298(2), 63–69. https://doi.org/10.1016/0165-1218(92)90030-4
- Nair, B., & Elmore, A. R. (2003). Final report on the safety assessment of sodium sulfite, potassium sulfite, ammonium sulfite, sodium bisulfite, ammonium bisulfite, sodium metabisulfite and potassium metabisulfite. International Journal of Toxicology, 22, 63–88. https://doi.org/10.1080/10915810305077x
- Niknahad, H., & O’Brien, P. J. (2008). Mechanism of sulfite cytotoxicity in isolated rat hepatocytes. Chemico-Biological Interactions, 174(3), 147–154. https://doi.org/10.1016/j.cbi.2008.05.032
- Oliphant, T., Mitra, A., & Wilkinson, M. (2012). Contact allergy to sodium sulfite and its relationship to sodium metabisulfite. Contact Dermatitis, 66(3), 128–130. https://doi.org/10.1111/j.1600-0536.2011.02029.x
- Silva, M. M., & Lidon, F. (2016). Food preservatives–An overview on applications and side effects. Emirates Journal of Food and Agriculture, 28(6), 366–373. https://doi.org/10.9755/ejfa.2016-04-351
- Stohs, S. J., & Miller, M. J. (2014). A case study involving allergic reactions to sulfur-containing compounds including, sulfite, taurine, acesulfame potassium and sulfonamides. Food and Chemical Toxicology, 63, 240–243. https://doi.org/10.1016/j.fct.2013.11.008
- Takahashi, M., Hasegawa, R., Furukawa, F., Toyoda, K., Sato, H., & Hayashi, Y. (1986). Effects of ethanol, potassium metabisulfite, formaldehyde and hydrogen peroxide on gastric carcinogenesis in rats after initiation with N-methyl-N'-nitro-N-nitrosoguanidine. Japanese Journal of Cancer Research GANN, 77(2), 118–124.
- Vally, H., Misso, N. L., & Madan, V. (2009). Clinical effects of sulphite additives. Clinical & Experimental Allergy, 39(11), 1643–1651. https://doi.org/10.1111/j.1365-2222.2009.03362.x
- Vasile, M. (2010). Sulfites and foods, toxicity and hypersensitivity. Journal of EcoAgriTourism, 6(4), 63–66.
- World Health Organization. (2017). Evaluation of certain food additives. World Health Organization Technical Report Series, 1000, 1–162.
- Yavuz-Kocaman, A., Rencuzogullari, E., Ila, H. B., & Topaktas, M. (2008). The genotoxic effect of potassium metabisulfite using chromosome aberration, sister chromatid exchange, micronucleus tests in human lymphocytes and chromosome aberration test in bone marrow cells of rats. Environmental and Molecular Mutagenesis, 49(4), 276–282. https://doi.org/10.1002/em.20382
- Zaloga, G. P., & Marik, P. (2003). Sulfite-induced propofol oxidation: A cause for radical concern. Critical Care Medicine, 31(3), 981–983. https://doi.org/10.1097/01.CCM.0000053526.68271.CD
- Zhang, X., Vincent, A. S., Halliwell, B., & Wong, K. P. (2004). A mechanism of sulfite neurotoxicity: Direct inhibition of glutamate dehydrogenase. Journal of Biological Chemistry, 279(41), 43035–43045. https://doi.org/10.1074/jbc.M402759200