Adverse Effect of Mixture of Food Additives on Some Biochemical Parameters in Male Albino Rats


  • Eman Hashem Radwan Damanhour university
  • Mohamed Mohamed Elghazaly Damanhour University
  • Hussein Khamis Hussein Alexandria University
  • Karolin Kamel Abdel Aziz Damanhour University
  • Amel Ibrahim Barakat Damanhour University



Nephrotoxicity-P53- Oxidative Stress- Food Additives- Male Rats


The present study investigated the unsafe impacts of sodium nitrite, sodium benzoate and their mixture which is utilized in fabricating of the food on some biochemical parameters in male albino rats. Rats (40) were divided into four groups as follows: group 1 used as the control, group II and III were treated orally with sodium nitrite nano2 (80 mg/kg BW) and sodium benzoate (SB) (200 mg/kg BW), respectively. Group IV was treated orally with a mixture of sodium nitrite and sodium benzoate. Rats took their respective doses every day for 8 weeks. The obtained results showed that sodium nitrite, sodium benzoate and their mixture (nano2 and SB)  initiated a diminished within in the activity of antioxidant enzymes (SOD, CAT, and GSH) within the kidney, while, MDA recorded a highly significant activity level within experimental groups. Urea and creatinine mean levels were were expanded within plasma of the experimental rats. In the histology of the kidney, sections appeared edema with few mononuclear leukocyte cellular infiltrations, shrinkage of glomeruli. The severity of these changes increased in the experimental group which treated by the mixture of sodium nitrite and sodium benzoate. Overexpression in p53 occurred in experimental groups that were treated by nano2, SB and their mixture. The present study concluded that the mixture of food additives can induce toxicity in the kidney of rats. It is obvious that food additives induced nephrotoxicity  within the kidney. It decreased the antioxidant enzymes (GSH, CAT, and SOD) and increased MDA. Increase tumor suppressor gene p53 in kidney tissue. Food added substances caused changes in biochemical parameters as in creatinine and urea. The utilization of food additives must be decreased. The presence of more than one type of food additives on our food and the usage of the mixture of sodium nitrite and sodium benzoate initiated changes in biochemical parameters and immune-histopathological changes.


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Author Biographies

Eman Hashem Radwan, Damanhour university

Faculty of Science, Zoology Department

Mohamed Mohamed Elghazaly, Damanhour University

Faculty of Science, Zoology Department

Hussein Khamis Hussein, Alexandria University

Faculty of Science, Zoology Department

Karolin Kamel Abdel Aziz, Damanhour University

Faculty of Science, Zoology Department

Amel Ibrahim Barakat, Damanhour University

Faculty of Science, Zoology Department


Ahmad, H., Masoud, V., & Ali, S. (2017). A comparative study of the effects of the two preservatives, sodium benzoate and potassium sorbate on Aspergillus niger and Penicillium notatum. Jundishapur Journal of Microbiology, 4, 301-307.

Cui, H., Gabriel, A. A., & Nakano, H. (2010). Antimicrobial efficacies of plant extracts and sodium nitrite against Clostridium botulinum. Food Control, 21(7), 1030-1036.‏

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.‏

AL-Mosaibih, M. A. (2013). Effects of monosodium glutamate and acrylamide on the liver tissue of adult Wistar rats. Life Science. Journal, 10(6), 35-42.‏

Kapil, V., Haydar, S. M., Pearl, V., Lundberg, J. O., Weitzberg, E., & Ahluwalia, A. (2013). Physiological role for nitrate-reducing oral bacteria in blood pressure control. Free Radical Biology and Medicine, 55, 93-100.‏

Abdulmumeen, H. A., Risikat, A. N., & Sururah, A. R. (2012). Food: Its preservatives, additives and applications. International Journal of Chemical and Biochemical Sciences, 1, 36-47.‏

Bearth, A., Cousin, M. E., & Siegrist, M. (2014). The consumer’s perception of artificial food additives: Influences on acceptance, risk and benefit perceptions.Food Quality and Preference, 38, 14-23.‏

Yılmaz, A., Fatma, N., Deniz, Y., & Hüseyin, A. (2008). Clastogenic effects of food additive citric acid in human peripheral lymphocytes. Cytotechnology 56, 137–144.

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.

El-Kholy, W. M., Hassan, H. A., & Nour, S. E. (2007). The role of black seed and/or bees honey in modulating the heart disorder induced by food additives in male rats. Egyptian Journal of Hospital Medicine, 28, 327-341.‏

El Ghazaly NA, EH Radwan, H Zaatout, MM Elghazaly, and Nour El Din Allam (2019). Beneficial effects of Fennel (Foeniculum vulgare) in treating obesity in rats. V(1), issue 2, pp 16-33. DOI. 10.14302/issn.2574-450x.jom-18-2484.

Paraskakis, E., Vergadi, E., Chatzimichael, A., & Bush, A. (2016). The role of flow-independent exhaled nitric oxide parameters in the assessment of airway diseases. Current topics in medicinal chemistry, 16(14), 1631-1642.‏

Heydaryinia, A., Veissi, M., & Sadadi, A. (2011). A comparative study of the effects of the two preservatives, sodium benzoate and potassium sorbate on aspergillus niger and penicillium notatum. Jundishapur journal of microbiology,4(4), 301-307.‏

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.‏

Tripathi, M., Khanna, S. K., & Das, M. (2007). Surveillance on use of synthetic colours in eatables vis a vis Prevention of Food Adulteration Act of India. Food Control, 18(3), 211-219.‏

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.‏

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.‏

Liman, N., Alan, E., Beyaz, F., & Gürbulak, K. (2013). Endothelial and inducible nitric oxide synthase (NOS) immunoreactivity and NOS-associated NADPH-diaphorase histochemistry in the domestic cat (Felis catus) testis.Theriogenology, 80(9), 1017-1032.‏

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.‏

Russell, K. E., & Roussel, A. J. (2007). Evaluation of the ruminant serum chemistry profile. Veterinary Clinics of North America: Food Animal Practice,23(3), 403-426.‏

Gladwin, M. T., Schechter, A. N., Kim-Shapiro, D. B., Patel, R. P., Hogg, N., Shiva, S., & Oldfield, E. H. (2005). The emerging biology of the nitrite anion.‏ National Chemistry Biology 1(6):308–314

Hsu, J., Arcot, J., & Lee, N. A. (2009). Nitrate and nitrite quantification from cured meat and vegetables and their estimated dietary intake in Australians.Food Chemistry, 115(1), 334-339.‏

Karakaya, M., Bayrak, E., & Ulusoy, K. (2011). Use of natural antioxidants in meat and meat products. Journal of Food Science and Engineering, 1(1), 1.‏

de Gonzalez, M. N., Hafley, B. S., Boleman, R. M., Miller, R. K., Rhee, K. S., & Keeton, J. T. (2008). Antioxidant properties of plum concentrates and powder in precooked roast beef to reduce lipid oxidation. Meat Science, 80(4), 997-1004.‏

Sturgeon, C. M., Kemmer, D., Anderson, H. J., & Roberge, M. (2006). Yeast as a tool to uncover the cellular targets of drugs. Biotechnology journal, 1(3), 289-298.‏

Hu, M., Wang, J., Cai, J., Wu, Y., & Wang, X. (2008). Analysis of sodium benzoate biotoxicity using atomic force microscope. Chinese Journal of Biotechnology, 24(8), 1428-1432.‏

Schwimmer, C., Rak, M., Lefebvre‐Legendre, L., Duvezin‐Caubet, S., Plane, G., & di Rago, J. P. (2006). Yeast models of human mitochondrial diseases: from molecular mechanisms to drug screening. Biotechnology journal, 1(3), 270-281.‏

Mamur, S., Yüzbaşıoğlu, D., Ünal, F., & Yılmaz, S. (2010). Does potassium sorbate induce genotoxic or mutagenic effects in lymphocytes?. Toxicology in vitro, 24(3), 790-794.‏

Hazan, R., Levine, A., & Abeliovich, H. (2004). Benzoic acid, a weak organic acid food preservative, exerts specific effects on intracellular membrane trafficking pathways in Saccharomyces cerevisiae. Applied and environmental microbiology, 70(8), 4449-4457.‏

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.‏

Ferreira, I. M., Mendes, E., Brito, P., & Ferreira, M. A. (2000). Simultaneous determination of benzoic and sorbic acids in quince jam by HPLC. Food Research International, 33(2), 113-117.‏

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.

Kohn, M. C., Melnick, R. L., Ye, F., & Portier, C. J. (2002). Pharmacokinetics of sodium nitrite-induced methemoglobinemia in the rat. Drug Metabolism and Disposition, 30(6), 676-683.‏

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.

Fawcett, J . K. And Scott, J. E., (1960). A rapid and precise method for the determination of urea. Journal of Clinical Pathology 13, 156-159.

Fabiny, D. L. (1971). Automated reaction-rate methods for determination of serum creatinine. Clinical Chemistry 17, 696-700.

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, 151-169.

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

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

Drury, R. A., Wallington, E. A., Carleton, S., (1980). Histological Techniques, fifth ed., Oxford University Press, London, New York, Toronoto, 241-242.

Budhram-Mahadeo, V., Morris, P., Ndisang, D., Irshad, S., Lozano, G., Pedley, B., & Latchman, D. S. (2002). The Brn-3a POU family transcription factor stimulates p53 gene expression in human and mouse tumour cells.Neuroscience letters, 334(1), 1-4.‏

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. Egypt. Ger. Soc. Zool, 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.

Laimer, M., Ebenbichler, C. F., Kaser, S., Sandhofer, A., Weiss, H., Nehoda, H., ... & Patsch, J. R. (2002). Weight loss increases soluble leptin receptor levels and the soluble receptor bound fraction of leptin. Obesity research, 10(7), 597-601.‏

Mozes, S., Sefcikova, Z., Lenhardt, L., & Racek, L. (2004). Obesity and changes of alkaline phosphatase activity in the small intestine of 40-and 80-day-old rats subjected to early postnatal overfeeding or monosodium glutamate.Physiological research, 53(2), 177-186.‏

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.‏

EH Radwan, A Abdel Mawgood, AZ Ghonim, MM elghazaly, R El nagar (2018). 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.

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.

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.‏

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

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.

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

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), 1058S-1062S.‏

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.‏

E.H. Radwan (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.

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

EH Radwan, 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.

EH Radwan, AA Hassan, GH Fahmy, SS El Shewemi, Sh Abdel Salam (2018). 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.

Radwan, Ebrahim Eissa, Atef MK Nassar, Yehia MM Salim, HO Hashem, KK Abdul Aziz and Nehal Abdel Hakeem (2019). Study of water pollutants in El Mahmoudia Agricultural irrigation stream at El Beheira Governorate, Egypt. J. Bioinforatics and Systems biology, 2 (1); 001-018. DOI. 10.26502/fjbsb004.

EH Radwan, HO Hashem, N S Youssef and Shalaby AM (2019). The effects of Zanzalacht on the gonotrophic cycle of the adult house fly Musca domestica. Journal of plant and animal ecology. V(1), issue 2, pp 23-39. DOI. 10.14302/issn.2637-6075.jpae-19-2586.



How to Cite

Radwan, E. H., Mohamed Elghazaly, M., Hussein, H. K., Abdel Aziz, K. K., & Barakat, A. I. (2020). Adverse Effect of Mixture of Food Additives on Some Biochemical Parameters in Male Albino Rats. JOURNAL OF ADVANCES IN BIOLOGY, 13, 1-13.