Skip to main content
SpringerLink
Log in

Furosine induces DNA damage and cell death in selected human cell lines: a strong toxicant to kidney Hek-293 cells

  • Published:
Food Science and Biotechnology Aims and scope Submit manuscript

Abstract

Ne-(2-furoylmethyl)-l-lysine (furosine) is well-known indicator of early stage of Maillard reaction in processed food. Yet the toxicological aspects associated with its exposure remain rarely studied. Here, we investigated the effects of furosine exposure on cell viability, DNA damage, and its mutagenic potential by using MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide), TUNEL assay (Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling assay), and Ames assay techniques on human cell lines, i.e., liver HepG-2, kidney Hek-293, neuronal SK-N-SH, and intestinal Caco-2, respectively. Our results showed that kidney Hek-293 cell line was the most sensitive to furosine exposure as significant reduction in cell viability and induction of DNA damage were observed at 50 mg/L concentration. In contrast, intestinal Caco-2 cell lines showed resistance to furosine exposure as DNA damage was only observed at 800 mg/L concentration of furosine. Ames assay indicated that furosine has no mutagenic effects on TA 100 and TA 1535 strains. Hence, this study suggests that furosine is a strong toxicant for kidney cells.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Troise AD, Fiore A, Wiltafsky M, Fogliano V. Quantification of Nε-(2-Furoylmethyl)-l-lysine (furosine), Nε-(Carboxymethyl)-l-lysine (CML), Nε-(Carboxyethyl)-l-lysine (CEL) and total lysine through stable isotope dilution assay and tandem mass spectrometry. Food Chem. 188: 357–364 (2015)

    Article  CAS  Google Scholar 

  2. Ahmed N. Advanced glycation endproducts role in pathology of diabetic complications. Diabetes Res. Clin. Pract. 67: 3–21 (2005)

    Article  CAS  Google Scholar 

  3. Hartog JW, Smit AJ, van Son WJ, Navis G, Gans RO, Wolffenbuttel BH, de Jong PE. Advanced glycation end products in kidney transplant dysfunction. Am. J. Kidney Dis. 43: 966–975 (2004)

    Article  CAS  Google Scholar 

  4. Basta G, Schmidt AM, De Caterina R. Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes. Cardio Vasc. Res. 63: 582–592 (2004)

    Article  CAS  Google Scholar 

  5. Takeuchi M, Yamagishi, SI. Possible involvement of advanced glycation end products (AGEs) in the pathogenesis of Alzheimer’s disease. Curr. Pharm. Des. 14: 973–978 (2008)

    Article  CAS  Google Scholar 

  6. Vitek MP, Bhattacharya K, Glendening JM, Stopa E, Vlassara H, Bucala R, Manogue K, Cerami A. Advanced glycation end products contribute to amyloidosis in Alzheimer disease. Proc. Natl. Acad. Sci. 91: 4766–4770 (1994)

    Article  CAS  Google Scholar 

  7. Delgado Andrade C, Seiquer I, Navarro MP. Comparative effects of glucose-lysine versus glucose methionine Maillard reaction products consumption: in vitro and in vivo calcium availability. Mol. Nutr. Food Res. 49: 679–684 (2005)

    Article  CAS  Google Scholar 

  8. Yaylayan VA, Huyghues Despointes A. Chemistry of Amadori products: analysis, kinetics, reactions and spectroscopic properties. Crit. Rev. Food Sci. Nutr. 34: 321–369 (1994)

    Article  CAS  Google Scholar 

  9. Erbersdobler HF, Somoza V. Forty years of furosine forty years of using Maillard reaction products as indicators of the nutritional quality of foods. Mol. Nutr. Food Res. 51: 423–430 (2007)

    Article  CAS  Google Scholar 

  10. Severin I, Dumont C, Jondeau Cabaton A, Graillot V & Chagnon MC. Genotoxic activities of the food contaminant 5-hydroxymethylfurfural using different in vitro bioassays. Toxicol. Lett. 192: 189–194 (2010)

    Article  CAS  Google Scholar 

  11. Somoza V, Wenzel E, Weiss C, Clawin-Rädecker I, Grübel N, Erbersdobler HF. Dose-dependent utilisation of casein-linked lysinoalanine, N-(epsilon)-fructoselysine and N(epsilon)-carboxymethyllysine in rats. Mol. Nutr. Food Res. 50: 833–841 (2006)

    Article  CAS  Google Scholar 

  12. Capuano E, Fogliano V. Acrylamide and 5-hydroxymethylfurfural (HMF): A review on metabolism, toxicity, occurrence in food and mitigation strategies. LWT-food science and technology. 44: 793–810 (2011)

    Article  CAS  Google Scholar 

  13. Hartkopf J, Erbersdobler HF. Stability of furosine during ion-exchange chromatography in comparison with reversephase HPLC. J. Chromatogr. 635: 151–154 (1993)

    Article  CAS  Google Scholar 

  14. Henle T, Zehtner G, Klostermeyer H. Fast and sensitive determination of furosine in food. Z. Lebensm. Unters. Forsch. 200: 235–237 (1995)

    Article  CAS  Google Scholar 

  15. Resmini P, Pellegrino L, Battelli G. Accurate quantification of furosine in milk and dairy products by a direct HPLC method. Ital. J. Food Sci. 3: 173–183 (1990)

    Google Scholar 

  16. Erbersdobler HF. Protein reactions during food processing and storage-their relevance to human nutrition. Bibl. Nutr. Dieta. 43: 140–150 (1989)

    Google Scholar 

  17. Arnoldi A, Resta D, Brambilla F, Boschin G, D’Agostina A, Sirtori E, O’Kane F. Parameters for the evaluation of the thermal damage and nutraceutical potential of lupin based ingredients and food products. Mol. Nutr. Food Res. 51: 431–436 (2007)

    Article  CAS  Google Scholar 

  18. Heyns K, Heukeshoven J, Brose KH. Degradation of fructose amino acids to N-(2-furoylmethyle) amino acids- intermediates in browning reaction. Angew Chem. Int. Ed. Engl. 7: 628–629 (1968)

    Article  CAS  Google Scholar 

  19. Finot PA, Bricout J, Viani R, Mauron J. identification of a new lysine derivative obtained upon acid hydrolysis of heated milk. Experientia. 24: 1097–1099 (1968)

    Article  CAS  Google Scholar 

  20. Finot PA, Viani R, Bricout J, Mauron J. Detection and identification of pyridosine, a second derivative obtained upon acid hydrolysis of heated milk. Experientia. 25: 134–135 (1969)

    Article  CAS  Google Scholar 

  21. Erbersdobler HF, Zucker H. Untersuchungen zum Gehalt an Lysin und verf_gbarem Lysin in Trockenmagermilch. Milchwiss. 21: 564–568 (1966)

    CAS  Google Scholar 

  22. Br-ggemann J, Erbersdobler HF. Fructoselysin als wichtigstes Reaktionsprodukt von Lysin mit Glucose bei Hitzesch digung von Lebens und Futtermitteln. Z. Lebensm. Unters. Forsch. 137: 137–143 (1968)

    Article  Google Scholar 

  23. Nicoletti I, Cogliandro E, Corradini C, Corradini D. Analysis of epsilon-N-2-furoylmethyl-l-lysine (furosine in concentrated milk by reversed phase chromatography with a microbore column. J. Liq. Chromatogr. Relat. Technol. 20: 719–729 (1997)

    Article  CAS  Google Scholar 

  24. Villamiel M, del Castillo M D, Corzo N, Olano A. Presence of furosine in honeys. J. Sci. Food Agric. 81(8): 790–793 (2001)

    Article  CAS  Google Scholar 

  25. Rada-Mendoza M, Olano A, Villamiel M. Rada Mendoza M, Olano A, Villamiel M. Furosine as indicator of Maillard reaction in jams and fruit-based infant foods. J. Agric. Food Chem. 50: 4141–4145 (2002)

    Article  CAS  Google Scholar 

  26. Rajchl A, Cizkova H, Voldrich M, Jiruskova M, Sevcik R. Evaluation of shelf life and heat treatment of tomato products. Czech j. food sci. 27: 130–133 (2009)

    Google Scholar 

  27. Seiquer I, Diaz Alguacil J, Delgado-Andrade C, Lopez-Frias M, Munoz Hoyos A, Galdo G, Navarro MP. Diets rich in Maillard reaction products affect protein digestibility in adolescent males aged 11-14 y. Am. J. Clin. Nutr. 83(5): 1082–1088 (2006)

    CAS  Google Scholar 

  28. Delgado-Andrade C, Seiquer I, Navarro MP, Morales FJ. Estimation of hydroxymethylfurfural availability in breakfast cereals. Studies in Caco-2 cells. Food Chem. Toxicol. 46(5): 1600–1607 (2008)

    Article  CAS  Google Scholar 

  29. Maron DM, Ames BM. Revised methods for the Salmonella mutagenicity test. Mutat. Res. 113: 173–215 (1983)

    Article  CAS  Google Scholar 

  30. Brusick DJ, Simmon VF, Rosenkranz HS, Ray VA, Stafford RS. An evaluation of the Escherichia coli WP2 and WP2 uvrA reverse mutation assay. Mutat. Res. 7: 169–190 (1980)

    Article  Google Scholar 

  31. Kumano K, Yokota S, Sakai T, Kobayashi N, Yoshida A, Yoshihara T, Shibata K, Izumi G, Wang H. Kinetic analysis of furosine and pentosidine in CAPD patients. Adv. Perit. Dial. 13: 53–57 (1999)

    Google Scholar 

  32. Abraham K, Gürtler R, Berg K, Heinemeyer G, Lampen A, Appel KE. Toxicology and risk assessment of 5-Hydroxymethyl furfural in food. Mol. Nutr. Food Res. 55: 667–678 (2011)

    Article  CAS  Google Scholar 

  33. Gugliucci A, Bendayan M. Renal fate of circulating advanced glycation end products (AGEs): evidence for re-absorption and catabolism of AGE-peptides by the proximal tubular cells. Diabetologia. 39: 149–160 (1996)

    Article  CAS  Google Scholar 

  34. Grillo MA, Colombatto S. Advanced glycation end products (AGEs): involvement in aging and in neurodegenerative diseases. Amino Acids. 35: 29–36 (2008)

    Article  CAS  Google Scholar 

  35. Yan SD, Chen X, Schmidt AM, Brett J, Godman G, Zou YS, Scott CW, Caputo C, Frappier T, Smith MA, Perry G, YENtt SH and Stern D. Glycated tau protein in Alzheimer disease: a mechanism for induction of oxidant stress. Proc. Natl. Acad. Sci. 91: 7787–7791 (1994)

    Article  CAS  Google Scholar 

  36. Kwak H, Lee M, Cho M. Interrelationship of apoptosis mutation and cell proliferation in N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) induced medaka carcinogenesis model. Aquat. Toxicol. 50: 317–329 (2000)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was financially supported by the National Natural Science Foundation of China (31501399), special fund for Agro-Scientific research in the public interest (201403071), Project of Risk Assessment on raw milk (GJFP2016008), and Agriculture Science and Technology Innovation Program (ASTIP-IAS12).

Author information

Authors and Affiliations

  1. Laboratory of Quality and Safety Risk Assessment for Dairy Products, Ministry of Agriculture, Beijing, People’s Republic of China

    Yasmeen Saeed, J. Q. Wang & N. Zheng

  2. Ministry of Agriculture Milk and Dairy Product Inspection Center (Beijing), Beijing, People’s Republic of China

    Yasmeen Saeed, J. Q. Wang & N. Zheng

  3. State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, People’s Republic of China

    Yasmeen Saeed, J. Q. Wang & N. Zheng

Authors
  1. Yasmeen Saeed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Q. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N. Zheng.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Saeed, Y., Wang, J.Q. & Zheng, N. Furosine induces DNA damage and cell death in selected human cell lines: a strong toxicant to kidney Hek-293 cells. Food Sci Biotechnol 26, 1093–1101 (2017). https://doi.org/10.1007/s10068-017-0131-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10068-017-0131-1

Keywords

Search

Navigation