Skip to main content

Advertisement

Log in

Assessment of hepato-renal damage and genotoxicity induced by long-term exposure to five permitted food additives in rats

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

The present study assessed the long-term daily administration of benzoic acid (BA), potassium sorbate (PS), chlorophyll (CPL), tartrazine (TAZ), and butylated hydroxyanisole (BHA) on hepato-renal changes and DNA damage in rats. Animals were orally administered with the 10 times of the acceptable daily intake (ADI) from each tested substance daily for 60 consecutive days. Blood, liver, and kidney samples were collected to evaluate hematological, biochemical, histopathological, and genotoxic alterations. The extent of liver and kidney damage was evaluated by comet assay and histopathologically. Significant reduction of leukocyte numbers and lymphocytes % in CPL- and TAZ-treated rats. However, significant increases in platelet count in all treated groups after 60 days were detected. The levels of serum transaminases enzymes (ALT, AST), alkaline phosphatase (ALP), and creatinine were significantly increased in all treatments except with BHA group, but no substantial differences were found in urea after 60 days. Aside from BHA, results of DNA damage revealed significant increases in tailed nuclei, tail moment, DNA% in the tail, and tail length in liver and kidney at different degrees. Moreover, the histopathological figures of liver and kidneys affirmed destructive and degenerative changes. The study indicates that most of the tested food additives may provoke genotoxicity and hepato-nephropathy, which could be serious for human health. Therefore, it is necessary to be informed about the hazardous effects of food additives and more attention should be focused towards using natural substitutes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Aboel-Zahab H, El-Khyat Z, Sidhom G, Awadallah R, Abdel-Al W, Mahdy K (1997) Physiological effects of some synthetic food colouring additives on rats. Boll Chim Farm 136:615–627

    CAS  Google Scholar 

  • Abd-Elhakim YM, Hashem MM, Anwar A, El-Metwally AE, Abo-El-Sooud K, Moustafa GG, Mouneir SM, Ali HA (2018) Effects of the food additives sodium acid pyrophosphate, sodium acetate, and citric acid on hemato-immunological pathological biomarkers in rats: relation to PPAR-α, PPAR-γ and TNFα signaling pathway Environmental Toxicology and Pharmacology https://doi.org/10.1016/j.etap.2018.07.002

  • Al-Seeni MN, El Rabey HA, Al-Hamed AM, Zamazami MA, (2018) Nigella sativa oil protects against tartrazine toxicity in male rats. Toxicol Rep 5:146–155

  • Alsuhaibani AM, ALkehayez NM, Alshawi Amal H, Al-Faris NA (2017) Effects of chlorophyll on body functioning and blood glucose levels. Asian J Clin Nutr 9:64–70

    Article  Google Scholar 

  • Amin K, Hameid HA II, Elsttar AA (2010) Effect of food azo dyes tartrazine and carmoisine on biochemical parameters related to renal, hepatic function and oxidative stress biomarkers in young male rats. Food Chem Toxicol 48:2994–2999

    Article  CAS  Google Scholar 

  • Ashour AA, Abdelaziz I (2009) Role of fast green on the blood of rats and the therapeutic action of vitamins C or E. Int J Integr Biol 6:6–11

    CAS  Google Scholar 

  • Bain B, Bates I, Laffan MA, Lewis SM (2012) Dacie and Lewis practical haematology, 11th edn. Churchill Livingstone, Elsevier, Philadelphia

    Google Scholar 

  • Bautista ARPL, Moreira E, Batista MS, Miranda M, Gomes I (2004) Subacute toxicity assessment of annatto in rat. Food Chem Toxicol 42:625–629

    Article  CAS  Google Scholar 

  • Bloom AS, Russell LJ, Weisskopf B, Blackerby JL (1988) Methylphenidate-induced delusional disorder in a child with attention deficit disorder with hyperactivity. J Am Acad Child Adolesc Psychiatry 27:88–89

    Article  CAS  Google Scholar 

  • Boindogurong J, Higaki T, Egashira Y, Sanada H (2005) Protective effect of butylated hydroxyanisole and butylated hydroxytoluene against acetaminophen-induced hepatotoxicity in rats. J Oleo Sci 54:153–159

    Article  CAS  Google Scholar 

  • Borzelleca J, Hallagan J (1988) Chronic toxicity/carcinogenicity studies of FD & C Yellow No. 5 (tartrazine) in rats. Food Chem Toxicol 26:179–187

    Article  CAS  Google Scholar 

  • Branen A, Davidson PM, Salminen S, Thorngate J (2001) Food additives. Taylor & Francis, New York

    Google Scholar 

  • De Boeck M, Touil N, De Visscher G, Vande PA, Kirsch-Volders M (2000) Validation and implementation of an internal standard in comet assay analysis. Mutat Res Genet Toxicol Environ Mutagen 469:181–197

    Article  Google Scholar 

  • Devlin J, David T (1992) Tartrazine in atopic eczema. Arch Dis Child 67:709–711

    Article  CAS  Google Scholar 

  • Duez P, Dehon G, Kumps A, Dubois J (2003) Statistics of the comet assay: a key to discriminate between genotoxic effects. Mutagenesis 18:159–166

    Article  CAS  Google Scholar 

  • El-Wahab HMFA, Moram GSE-D (2013) Toxic effects of some synthetic food colorants and/or flavor additives on male rats. Toxicol Ind Health 29:224–232

    Article  CAS  Google Scholar 

  • Frankel EN (1998) Free radical oxidation. In: Frankel EN (ed) Lipid oxidation. The Oily Press, Scotland, pp 13–22

    Google Scholar 

  • Hashem MM, Atta AH, Arbid MS, Nada SA, Asaad GF (2010) Immunological studies on amaranth, sunset yellow and curcumin as food colouring agents in albino rats. Food Chem Toxicol 48:1581–1586

    Article  CAS  Google Scholar 

  • Hassan RI, Raheem GSA (2016) Effect of feeding benzoic acid on performance of broiler chickens journal of advanced. Vet Res 6:118–122

    Google Scholar 

  • Himri I et al (2011) A 90-day oral toxicity study of tartrazine, a synthetic food dye, in wistar rats. Group 300:00

    Google Scholar 

  • Hood W (2012) A–Z of clinical chemistry: a guide for the trainee. Springer Science & Business Media

  • Kahl R, Kappus H (1993) Toxicology of the synthetic antioxidants BHA and BHT in comparison with the natural antioxidant vitamin E. Z Lebensm Unters Forsch 196:329–338

    Article  CAS  Google Scholar 

  • King CM, Land SJ, Jones RF, Debiec-Rychter M, Lee M-S, Wang CY (1997) Role of acetyltransferases in the metabolism and carcinogenicity of aromatic amines. Mutat Res Fundam Mol Mech Mutagen 376:123–128

    Article  CAS  Google Scholar 

  • Kitamura Y, Nishikawa A, Furukawa F, Nakamura H, Okazaki K, Umemura T, Imazawa T, Hirose M (2003) A subchronic toxicity study of shea nut color in Wistar rats. Food Chem Toxicol 41:1537–1542

    Article  CAS  Google Scholar 

  • Maki T, Suzuki Y (1985) Benzoic acid and derivatives. In: Ullmann’s encyclopedia of industrial chemistry. Vol. A3. Weinheim, Published by VCH Verlagsgesell schaft, Germany, pp 555–568

  • Mamur S, Yüzbaşıoğlu D, Ünal F, Yılmaz S (2010) Does potassium sorbate induce genotoxic or mutagenic effects in lymphocytes? Toxicol in Vitro 24:790–794

    Article  CAS  Google Scholar 

  • Mpountoukas P, Pantazaki A, Kostareli E, Christodoulou P, Kareli D, Poliliou S, Mourelatos C, Lambropoulou V, Lialiaris T (2010) Cytogenetic evaluation and DNA interaction studies of the food colorants amaranth, erythrosine and tartrazine. Food Chem Toxicol 48:2934–2944

    Article  CAS  Google Scholar 

  • Myllyperkiö M, Koski T, Vilpo L, Vilpo J (1999) Gama-irradiation-induced DNA single-and double-strand breaks and their repair in chronic lymphocytic leukemia cells of variable radiosensitivity. Hematol Cell Ther 41:95–103

    Article  Google Scholar 

  • Okubo T, Yokoyama Y, Kano K, Kano I (2004) Molecular mechanism of cell death induced by the antioxidant tert-butylhydroxyanisole in human monocytic leukemia U937 cells. Biol Pharm Bull 27:295–302

    Article  CAS  Google Scholar 

  • Østergaard G, Knudsen I (1998) The applicability of the ADI (acceptable daily intake) for food additives to infants and children. Food Addit Contam 15:63–74

    Article  Google Scholar 

  • Paget GE, Barnes GM (1964) Evaluation of drug activities, vol 1. Academic Press, London

    Google Scholar 

  • Pandey H, Kumar V, Roy B (2014) Assessment of genotoxicity of some common food preservatives using Allium cepa L. as a test plant. Toxicol Rep 1:300–308

    Article  CAS  Google Scholar 

  • Pressinger R (1997) Environmental circumstances that can damage the developing brain, graduate student research project conducted at the University of South Florida. J Pediatr 92:64–67

    Google Scholar 

  • Richard RT, N.J Totowa (1995) The history of food preservation. Technology in Food Production, 152

  • Rus V, Gherman C, Miclăuş V, Mihalca A, Nadăş G (2010) Comparative toxicity of food dyes on liver and kidney in guinea pigs: a histopathological study. Ann RSCB 15:161–165

    Google Scholar 

  • Sasaki YF, Kawaguchi S, Kamaya A, Ohshita M, Kabasawa K, Iwama K, Taniguchi K, Tsuda S (2002) The comet assay with 8 mouse organs: results with 39 currently used food additives. Mutat Res Genet Toxicol Environ Mutagen 519:103–119

    Article  CAS  Google Scholar 

  • Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191

    Article  CAS  Google Scholar 

  • Sugihara N, Tsuruta Y, Furuno K (1998) Effect of potassium sorbate on cellular GSH level and lipid peroxidation in cultured rat hepatocytes. Biol Pharm Bull 21:524–526

    Article  CAS  Google Scholar 

  • Sulai NH, Tefferi A (2012) Why does my patient have thrombocytosis? Hematol Oncol Clin 26:285–301

    Article  Google Scholar 

  • Timbrell JA, Marrs TC (2009) Biotransformation of xenobiotics. General, Applied and Systems Toxicology

  • Yang X, Schnackenberg LK, Shi Q, Salminen WF (2014) Chapter 13 – Hepatic toxicity biomarkers. In: Gupta RC (ed) Biomarkers in Toxicology. Academic Press, Boston, pp 241–259 https://doi.org/10.1016/B978-0-12-404630-6.00013-0

  • Yılmaz S, Unal F, Aksoy H, Yuzbasıoglu D, Celik M (2008) Cytogenetic effects of citric acid and benzoic acid on allium chromosomes. Fresen Environ Bull 17:1029–1037

    Google Scholar 

Download references

Acknowledgments

This work was funded by Cairo University, Project entitled “Assessment of Residual patterns and Genotoxicity of some food additives using LMRS (laser molecular Raman spectroscopy).”

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yasmina M. Abd-Elhakim.

Additional information

Responsible editor: Philippe Garrigues

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abo-EL-Sooud, K., Hashem, M.M., Badr, Y.A. et al. Assessment of hepato-renal damage and genotoxicity induced by long-term exposure to five permitted food additives in rats. Environ Sci Pollut Res 25, 26341–26350 (2018). https://doi.org/10.1007/s11356-018-2665-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-018-2665-z

Keywords

Navigation