The Possible Effects of Sodium Nitrite and Sodium Benzoate as Food Additives on The Liver in Male Rats


  • Eman Hashem Radwan Damanhour University
  • MM Elghazaly Damanhour University
  • KK Abdel Aziz Damanhour University
  • AI Barakat Damanhour University
  • H Kh Hussein Alexandria University



Hepatotoxicity-P53, Sodium Nitrite, Sodium Benzoate, Food Additives, Male Rats


Common food additives endorsed by Food and drug Organization "FDA" are utilized to preserve taste. The display think about examined the perilous impacts of sodium nitrite, sodium benzoate and their blend which utilized in fabricating of the food additives on a few biochemical parameters and  histo-pathological examination in male rats. Male rats were divided into four groups; group I utilized as control, group II and III were treated orally with sodium nitrite NaNO2 (80 mg/kg BW) and sodium benzoate (SB) (200 mg/kg BW), separately. Group IV was treated orally with the blend of sodium nitrite and sodium benzoate. Rats were managed their dosages each day for 8 weeks. It appeared that sodium nitrite, sodium benzoate and their blend (NaNO2 and SB) initiated a critical increment within the serum levels of aspartate aminotransferase "AST", alanine aminotransferase "ALT". Antioxidant proteins (GSH, CAT) within the liver tissue recorded a decrease while, MDA recorded an increase action level within the tested groups. Over expression in p53 happened in exploratory groups which were treated by NaNO2, SB and their blend. The present study concluded that the blend of food additives can actuate harmfulness within the liver of rats. In conclusion, it is noted that food additives induced hepatotoxicity within the liver. It diminished the antioxidant chemicals (GSH, CAT) and elevated the activity level of the MDA and increment tumor silencer quality p53 in liver tissue. Food additive substances caused changes in biochemical parameters (ALT, AST). The utilization of food additives must be diminished. The usage of the mixture of sodium nitrite and sodium benzoate induced changes in biochemical parameters and immune-histopathology.    


Download data is not yet available.

Author Biographies

Eman Hashem Radwan, Damanhour University

Faculty of Science, Zoology department, Egypt

MM Elghazaly, Damanhour University

Faculty of Science, Zoology Department, Egypt

KK Abdel Aziz, Damanhour University

Faculty of Science, Zoology Department, Egypt

AI Barakat, Damanhour University

Faculty of Science, Zoology department, Egypt

H Kh Hussein, Alexandria University

Faculty of Science, Zoology Department, Egypt


Lau, K., McLean, W. G., Williams, D. P., & Howard, C. V. (2005). Synergistic interactions between commonly used food additives in a developmental neurotoxicity test. Toxicological Sciences, 90(1), 178-187.‏

Stafford, K. (2014). Sheep veterinarians and the welfare of sheep: No simple matter. Small Ruminant Research, 118(1), 106-109.‏

Soriano, V. S., e Sá, J., Junior, H. P. R., Torbitz, V. D., Moresco, R. N., Stefani, L. M., & Da Silva, A. S. (2015). Postpartum nitric oxide, oxidants and antioxidants levels in ewes and their lambs. Small Ruminant Research, 123(1), 13-16.‏

Bateman, B., Warner, J. O., Hutchinson, E., Dean, T., Rowlandson, P., Gant, C., & Stevenson, J. (2004). The effects of a double blind, placebo controlled, artificial food coloring and benzoate preservative challenge on hyperactivity in a general population sample of preschool children. Archives of Disease in Childhood, 89(6), 506-511.

Deger, S., Deger, Y., Bicek, K., Ozdal, N., & Gul, A. (2009). Status of lipid peroxidation, antioxidants, and oxidation products of nitric oxide in equine babesiosis: status of antioxidant and oxidant in equine babesiosis. Journal of Equine Veterinary Science, 29(10), 743-747.‏

Toldrá, F., Aristoy, M. C., & Flores, M. (2009). Relevance of nitrate and nitrite in dry-cured ham and their effects on aroma development. Grasas y aceites, 60(3), 291-296.‏

Chui, J. S. W., Poon, W. T., Chan, K. C., Chan, A. Y. W., & Buckley, T. A. (2005). Nitrite‐induced methaemoglobinaemia –aetiology ,diagnosisand treatment. Anaesthesia, 60(5), 496-500.‏

Furuno, Y., Morishita, T., Toyohira, Y., Yamada, S., Ueno, S., Morisada, N. & Tanimoto, A. (2011). Crucial vasculo protective role of the whole nitric oxide synthase system in vascular lesion formation in mice: Involvement of bone marrow-derived cells. Nitric Oxide, 25(3), 350-359.‏

Romero-Barrios, P., Hempen, M., Messens, W., Stella, P., & Hugas, M. (2013). Quantitative microbiological risk assessment (QMRA) of food-borne zoonoses at the European level. Food Control, 29(2), 343-349.‏

Milkowski, A., Garg, H. K., Coughlin, J. R., & Bryan, N. S. (2010). Nutritional epidemiology in the context of nitric oxide biology: A risk–benefit evaluation for dietary nitrite and nitrate. Nitric oxide, 22(2), 110-119.‏

Mellor, D. J., & Stafford, K. J. (2004). Animal welfare implications of neonatal mortality and morbidity in farm animals. The Veterinary Journal, 168(2), 118-133.‏

Bremer, V., Leitmeyer, K., Jensen, E., Metzel, U., Meczulat, H., Weise, E., & Ammon, A. (2004). Outbreak of Salmonella Goldcoast infections linked to consumption of fermented sausage. Epidemiology and infection, 132(5), 881-887.‏

Alexander, D. D., Weed, D. L., Miller, P. E., & Mohamed, M. A. (2015). Red meat and colorectal cancer: a quantitative update on the state of the epidemiologic science. Journal of the American College of Nutrition, 34(6), 521-543.

Radwan EH (2015). Surveillance ecological study of cellular responses in three marine edible bivalve species to Cd present in their marine habitat, Mediterranean sea in Alexandria, Egypt. J. of Advances in biology Vol. 7, No 2, pp. 1319-1337.

Radwan EH (2016): Determination of total hydrocarbon and its relation to amino acid found in two bivalve edible species from Alexandria and El Ismailia coast, Egypt. J of Advances in biology, V(9), No. (5), pp. 1834-1844.

Radwan EH (2018). Chapter of Soil Toxicology: Potential Approach on the Egyptain Agro-Environment. Springer, DOI: 10.1007/698-2018-242.

Celi, P., Di Trana, A., & Claps, S. (2010). Effects of plane of nutrition on oxidative stress in goats during the peripartum period. The Veterinary Journal, 184(1), 95-99.

Casamassima, D., Palazzo, M., Martemucci, G., Vizzarri, F., & Corino, C. (2012). Effects of verbascoside on plasma oxidative status and blood and milk production parameters during the peripartum period in Lacaune ewes. Small Ruminant Research, 105(1), 1-8.

Radwan EH, Sh Shaker Hamed, G Ahmed Saad (2014): Temporal and Spatial Effects on Some Physiological Parameters of the Bivalve Lithophaga lithophaga (Linnaeus, 1758) from Coastal Regions of Alexandria, Egypt. Open Journal of Ecology, 4, 732-743.

Radwan EH, Gaber A. Saad, Sherifa Sh. Hamed. (2016). Ultrastructural study on the foot and the shell of the oyster, Pinctada radiata (leach, 1814), (Bivalvia: Petridae). Journal of Bioscience and Applied Research, Vol.2, No.4:274-283.Conference paper: The First International Conference of Society of Pathological Biochemistry and hematology, February 16, Faculty of Science Menoufia University, Egypt.

Radwan EH, GH Fahmy, Mennat Allah Kh Saber, and Mohie El Din Kh Saber (2017). The impact of some organic and inorganic pollutants on fresh water (Rashid branch, River Nile), Egypt. J. of Advances in biology V (10), No.(2), pp. 2133-2145.

Radwan EH, A Abdel Mawgood, AZ Ghonim, R El nagar (2018a). The possibility of using the fresh water bivalve, Spathopsis rubins, in the Nile River, El Mahmoudia water stream as bioindicator for pollution. International Journal of Limnology, V(1), issue(1),pp 1-23.

Radwan EH, AA Hassan, GH Fahmy, SS El Shewemi, Sh Abdel Salam (2018b). Impact of environmental pollutants and parasites on the ultrastructure of the Nile bolti, Oreochromis auruis. Journal of bioscience and applied research .V (4), No. (1), pp. 58-83.

Hosoda, K., Miyaji, M., Matsuyama, H., Haga, S., Ishizaki, H., & Nonaka, K. (2012). Effect of supplementation of purple pigment from anthocyanin-rich corn (Zea mays L.) on blood antioxidant activity and oxidation resistance in sheep.Livestock Science, 145(1), 266-270.‏

Iammarino, M., Di Taranto, A., & Cristino, M. (2013). Endogenous levels of nitrites and nitrates in wide consumption foodstuffs: results of five years of official controls and monitoring. Food chemistry, 140(4), 763-771.‏

Firmino, A. (2014). Food and Consumption: How a Meal can Change the World.Editors: Mary Cawley, Ana Maria Bicalho, Lucette Laurens, The Sustainability of Rural Systems: global and local challenges and opportunities, 84-93.‏

Al-Shammari, E., Bano, R., Khan, S., Shankity. I. (2014). The Effect of Preservatives and Flavour Additive on the Production of Oxygen-Free Radicals by Isolated Human Neutrophils. International Journal of Nutrition and Food Sciences, 3 (3), 210-215.

Elghazaly, MM, H Kh Hussein, KK Abel Aziz, AI Barakat, and EH Radwan (2020). Adverse effect of mixture of food additives on some biochemical parameters in male albino rats. Journal of advances in biology, 13,(1-13).

Hassan, H., El-Kholym, W., & Nour, S. (2008). Adverse effect of some food additives on growth rate and some biochemical and hematological parameters in male albino rats. Role Black Seed Bees Honey Protective Agents, 35, 25-51.

Khan, J.A. (2003). Biochemical effects of a methanolic extract of cloves on rats and some enzymes. Saudi J. Biol. Sci.10 (1): 72-79.

Oyewole, O. I., Dere, F. A., & Okoro, O. E. (2012). Sodium Benzoate Mediated Hepatorenal Toxicity in Wistar Rat: Modulatory Effects of Azadirachta indica (Neem) Leaf. European Journal Med Plants ; 21, 11-18.

Schumann, G. and Klauke, R. (2003). New IFCC reference procedures for the determination of catalytic activity concentrations of five enzymes in serum: preliminary upper reference limits obtained in hospitalized subjects. Clininical Chimica Acta, 327, 69-79.

Gornall, A. G., Bardawill, C. J., David, M. M. (1949). Determination of serum proteins by means of the biuret reaction. The Journal of Biological Chemistry 177, 751-766.

Doumas, B. T., Watson, W. A., & Biggs, H. G. (1977). Albumin standards and the measurement of serum albumin with bromocersol green. Clinica Chimica Acta 31, 87-96.

Tappel, A. L. and Zalkin, H., (1959). Inhibition of lipid peroxidation in mitochondria by vitamin E. Archives of Biochemistry and Biophysics 80: 333-336.

Jollow, D. J., Michell, J. R., Zampaglionic, Gillete, J. R. (1974). Bromoibenzene-induced liver necrosis: Protective role of glutathione and evidence for 3,4- Bromobenzene oxide as hepatotoxic metabolite. Pharmacology 11, 151-16

Luck, H., (1974). Catalase. In: Bergmayer, M. V. (Ed.), Method of Enzymatic Analysis. Verlage Chemic. Academic press, New York p. 885.

Mishra, H. P. & Fridovich, I., (1972). The role of superoxide anion in the the autoxidation of epinephrine and a simple assay for superoxidedismutase. The Journal of Biological Chemistry 247, 3170-3175.

Budhram-Mahadeo, V., Morris, P. J., Smith, M. D., Midgley, C. A., Boxer, L. M., & Latchman, D. S. (1999). p53 suppresses the activation of the Bcl-2 promoter by the Brn-3a POU family transcription factor. Journal of Biological Chemistry, 274(21), 15237-15244.‏

Hassan, H. A. (2007). The possible protective role of bees honey against hazard effects of some synthetic food additives on the kidney functions of male rats. Journal of the Egyptian Society of Toxicology, 36, 13-21.‏

Abdeen, A. M., El-Shayeb, A. F., Othman, A. I., & El-Agamy, S. H. (2008). Histopathological and histochemical studies of the influence of garlic oil against sodium nitrite induced toxicity in the liver and lungs of albino rat Journal. Egyptian Germany Society Zoology, 55, 261-287.

Patsoukis, N., & Georgiou, C. D. (2007). Effect of sulfite–hydrosulfite and nitrite on thiol redox state, oxidative stress and sclerotial differentiation of filamentous phytopathogenic fungi. Pesticide biochemistry and physiology, 88(2), 226-235.‏

Kim, S., Nah, S.Y. and Rhim, H. (2008). Neuroprotective effects of ginsengsaponins against L-type Ca2+ channel-mediated cell death in rat cortical neurons. Biochem. Biophys. Res. Commun. 365, 399–405.

Kalantari, H., & Salehi, M. (2001). The protective effect of garlic oil on hepatotoxicity induced by acetaminophen in mice and comparison with N-acetylcysteine. Saudi medical journal, 22(12), 1080-1084.‏

Abdelaziz, I., & Ashour, A. E. R. A. (2011). Effect of saccharin on albino rats’ blood indices and the therapeutic action of vitamins C and E. Human & experimental toxicology, 30(2), 129-137.‏

Hassan, H. A., Hafez, H. S., & Zeghebar, F. E. (2010). Garlic oil as a modulating agent for oxidative stress and neurotoxicity induced by sodium nitrite in male albino rats. Food and Chemical Toxicology, 48(7), 1980-1985.‏

Sadowska, J., & Kuchlewska, M. (2011). Effect of diet composition and mixture of selected food additives on the erythrocytic system and iron metabolism in peripheral blood of male rats. Acta Scientiarum Polonorum Technologia Alimentaria, 10(4), 497-506.‏

Hussiena, H. M., Abdoub, H. M., Yousef, M. I., (2013). Cypermethrin induced damage in genomic DNA and histopathological changes in brain and haematotoxicity in rats: The protective effect of sesame oil. Brain Research Bulletin, 92: 76-83.

McCann, D., Barrett, A., Cooper, A., Crumpler, D., Dalen, L., Grimshaw, K. & Sonuga-Barke, E. (2007). Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial. The lancet, 370(9598), 1560-1567.‏

El-Wakf, A. M., Hassan, H. A., El-Said, F. G., & El-Said, A. (2009). The association between nitrite contamination of drinking water and changes in methemoglobin level other hematological parameters in young and adult male rats Journal Egyptian Society of Toxicology, 49, 91-96.‏

Ashaolu, J. O., Ukwenya, V. O., Okonoboh, A. B., Ghazal, O. K., & Jimoh, A. A. G. (2011). Effect of monosodium glutamate on hematological parameters in Wistar rats. International Journal of Medicine and Medical Sciences, 3(6), 219-222.‏

Freeman, M. (2006). Reconsidering the effects of monosodium glutamate: a literature review. Journal of the American Association of Nurse Practitioners,18(10), 482-486.‏

Farombi, E. O., & Onyema, O. O. (2006). Monosodium glutamate-induced oxidative damage and genotoxicity in the rat: modulatory role of vitamin C, vitamin E and quercetin. Human & experimental toxicology, 25(5), 251-259.‏

Onyema, O. O., Farombi, E. O., Emerole, G. O., Ukoha, A. I., & Onyeze, G. O. (2006). Effect of vitamin E on monosodium glutamate induced hepatotoxicity and oxidative stress in rats.‏ Indian Journal of Biochemistry & Bio- physics, 43 (1), 20-24.

Chung, R. T., Casson, D. R., Murray, G., Song, S., Grinspoon, S., & Hadigan, C. (2003). Alanine aminotransferase levels predict insulin resistance in HIV lipodystrophy. JAIDS Journal of Acquired Immune Deficiency Syndromes, 34(5), 534-536.‏

Vinodini, N. A., Nayanatara, A. K., Ramaswamy, C., Ranade, A. V., Kini, R. D., Gowda, K. M. & Bhat, R. (2010). Study on evaluation of monosodium glutamate induced oxidative damage on renal tissue on adult Wistar rats. Journal of Chinese Clinical Medicine, 5(3) 144-147.‏

Cadenas, S. and Cadenas, A. M. (2002). Fighting the Stranger- Antioxidant Protection against Endotoxin Toxicity. Toxicology, 180 (1), 45-63.

Jackson, J., Patterson, A. J., MacDonald-Wicks, L., & McEvoy, M. (2017). The role of inorganic nitrate and nitrite in CVD. Nutrition Research Reviews, 1-18.‏

Khan, J.A. 2003. Biochemical effects of a methanolic extract of cloves on rats and some enzymes. Saudi J. Biol. Sci.10 (1): 72-79.

Wawrzyniak, A. (2000). Effect of diet with added pectin on rats given sodium nitrite. Polish journal of food and nutrition sciences, 9(1), 57-60.‏

Huber, J. C., Brender, J. D., Zheng, Q., Sharkey, J. R., Vuong, A. M., Shinde, M. U., & Romitti, P. A. (2013). Maternal dietary intake of nitrates, nitrites and nitrosamines and selected birth defects in offspring: a case-control study.Nutrition journal, 12(1), 34-42.‏

Geha, R. S., Beiser, A., Ren, C., Patterson, R., Greenberger, P. A., Grammer, L. C., & Corren, J. (2000). Review of alleged reaction to monosodium glutamate and outcome of a multicenter double-blind placebo-controlled study. The Journal of nutrition, 130(4), 1058-1062.‏

Sequeira, S., Rao, A. V., & Rao, A. (2012). Increased oxidative stress and altered antioxidants status in patients with chronic allergic rhinitis.‏ Adv. Biosci. Biotechnol.3, 951-956.

Vinodini, N. A., Nayanatara, A. K., Ramaswamy, C., Ranade, A. V., Kini, R. D., Gowda, K. M., ... & Bhat, R. (2010). Study on evaluation of monosodium glutamate induced oxidative damage on renal tissue on adult Wistar rats. Journal of Chinese Clinical Medicine, 5(3) 144-147.‏




How to Cite

Radwan, E. H., MM Elghazaly, KK Abdel Aziz, AI Barakat, & H Kh Hussein. (2020). The Possible Effects of Sodium Nitrite and Sodium Benzoate as Food Additives on The Liver in Male Rats. JOURNAL OF ADVANCES IN BIOLOGY, 13, 14–30.