Advertisement

DNA damage in kidney and parenchymal and non-parenchymal liver cells of adult Wistar rats after subchronic oral treatment with tembotrione

  • Vilena KašubaEmail author
  • Vedran Micek
  • Alica Pizent
  • Blanka Tariba Lovaković
  • Davor Želježić
  • Mirta Milić
  • Nevenka Kopjar
Research Article
  • 24 Downloads

Abstract

DNA damage in the liver and kidney cells of adult male Wistar rats was studied using the comet assay after a 28-day oral administration of tembotrione at doses of 0.0007, 0.0013 and 0.7 mg/kg b.w./day [AOEL (acceptable operator exposure level), REL (residual exposure level) and 1000× AOEL]. As a descriptor of DNA damage, tail intensity was used. Antioxidant status was assessed by activity of glutathione peroxidase (GPx). Significant DNA damage was recorded in the kidney cells at all three doses as compared to negative control. In parenchymal liver cells, significant DNA damage was observed in AOEL and 1000× AOEL doses, while in non-parenchymal liver cells, only AOEL-treated group was significantly different compared to negative control. In both types of liver cells, REL and 1000× AOEL doses were significantly different from the AOEL dose. No significant changes in GPx activity compared to control were observed at any exposure level. The results of the present study suggest that repeated in vivo exposure to tembotrione led to low-level DNA instability in kidney and liver cells. Exposure to the highest tembotrione dose showed a relatively weak response with the alkaline comet assay. Further research should focus on the effects of this herbicide in other models along with different exposure scenarios.

Keywords

DNA damage Parenchymal and non-parenchymal liver cells Kidney cells Tembotrione 

Notes

Funding information

This work was financially supported by the project Organic Pollutants in Environment – Markers and Biomarkers of Toxicity (OPENTOX), funded by the Croatian Science Foundation (grant number 8366).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Asahi J, Kamo H, Baba R, Doi Y, Yamashita A (2010) Bisphenol A induces endoplasmic reticulum stress-associated apoptosis in mouse non-parenchymal hepatocytes. Life Sci 87:431–438.  https://doi.org/10.1016/j.lfs.2010.08.007 CrossRefGoogle Scholar
  2. Azqueta A, Collins AR (2013) The essential comet assay: a comprehensive guide to measuring DNA damage and repair. Arch Toxicol 87(6):949–968.  https://doi.org/10.1007/s00204-013-1070-0 CrossRefGoogle Scholar
  3. Bailey SA, Zidell RH, Perry RW (2004) Relationship between organ weight and body/brain weight in the rat: what is the best analytical endpoint? Toxicol Pathol 32:448–466.  https://doi.org/10.1080/01926230490465874 CrossRefGoogle Scholar
  4. Bale SS, Golberg I, Jindal R, McCarty WJ, Luitje M, Hegde M, Bhushan A, Usta OB, Yarmush ML (2015) Long-term co-culture strategies for primary hepatocytes and liver sinusoidal endothelial cells. Tissue Engineering Part C, Methods 21:413–422.  https://doi.org/10.1089/ten.TEC.2014.0152 CrossRefGoogle Scholar
  5. Bale SS, Geerts S, Jindal R, Yarmush ML (2016) Isolation and co-culture of rat parenchymal and non-parenchymal liver cells to evaluate cellular interactions and response. Sci Rep 6:25329.  https://doi.org/10.1038/srep25329 CrossRefGoogle Scholar
  6. Beaudegnies R, Edmunds AJ, Fraser TE, Hall RG, Hawkes TR, Mitchell G, Schaetzer J, Wendeborn S, Wibley J (2009) Herbicidal 4-hydroxyphenylpyruvate dioxygenase inhibitors-a review of the triketone chemistry story from a Syngenta perspective. Bioorg Med Che. 17:4134–4152.  https://doi.org/10.1016/j.bmc.2009.03.015 CrossRefGoogle Scholar
  7. Belsten J, Wright A (1995) European Community: FLAIR common assay for whole-blood glutathione peroxidase (GSH-Px); results of an inter-laboratory trial. Eur J Clin Nutr 49:921–927Google Scholar
  8. Bindhu M, Yano B, Sellers RS, Perry R, Morton D, Roome N, Johnson JK, Schafer K (2007) Evaluation of organ weight for rodent and non-rodent toxicity studies:a review of regulatory guidelines and a survey of current topics. Toxicol Pathol 35:742–750CrossRefGoogle Scholar
  9. Bradford MM (1976) A rapid and sensitive assay for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254Google Scholar
  10. Brigelius-Flohé R (1999) Tissue-specific functions of individual glutathione peroxidases. Free Radic Biol Med 27:951–965CrossRefGoogle Scholar
  11. Choucroun P, Gillet D, Dorange G, Sawicki B, Dewitte JD (2001) Comet assay and early apoptosis. Mutat Res-Fundam Mol Mech Mutagen 478:89–96.  https://doi.org/10.1016/S0027-5107(01)00123-3 CrossRefGoogle Scholar
  12. Collins AR (2004) The comet assay for DNA damage and repair. Mol Biotechnnol 26:249–261CrossRefGoogle Scholar
  13. Dey A, Lakshmanan J (2013) The role of antioxidants and other agents in alleviating hyperglycemia mediated oxidative stress and injury in liver. Food Funct 4:1148–1184.  https://doi.org/10.1039/c3fo30317a CrossRefGoogle Scholar
  14. Dobashi K, Asayama K, Nakane T, Kodera K, Hayashibe H, Nakazawa S (2001) Induction of glutathione peroxidase in response to inactivation by nitric oxide. Free Radic Res 35:319–327CrossRefGoogle Scholar
  15. Esch MB, Prot J-M, Wang YI, Miller P, Llamas-Vidales JR, Naughton BA, Applegate DR, Shuler ML (2015) Multi-cellular 3D human primary liver cell culture elevates metabolic activity under fluidic flow. Lab on a Chip 15:2269–2277.  https://doi.org/10.1039/c5lc00237k CrossRefGoogle Scholar
  16. European Food Safety Authority (EFSA) (2013) Conclusion on the peer review of the pesticide risk assessment of the active substance tembotrione. EFSA J. 11(3):3131–3181.  https://doi.org/10.2903/j.efsa.2013.3131 http://www.efsa.europa.eu/efsajournal CrossRefGoogle Scholar
  17. Fairbairn DW, Olive PL, O Neill K (1995) The comet assay: a comprehensive review. Mutat Res-Fund Mol Mech Mutagen 339:37–59Google Scholar
  18. Jenne CN, Kubes P (2013) Immune surveillance by the liver. Nat Immunol 14:996–1006.  https://doi.org/10.1038/ni.2691 CrossRefGoogle Scholar
  19. Karabulut AB, Gui M, Karabulut E, Kiran TR, Ocak SG, Otlu O (2010) Oxidant and antioxidant activity in rabbit livers treated with zoledronic acid. Transplant Proc 42:3820–3822.  https://doi.org/10.1016/transproceed.2010.06.017 CrossRefGoogle Scholar
  20. Kayanoki Y, Fujii J, Islam KN, Suzuki K, Kawata S, Matsuzawa Y, Taniguchi N (1996) The protective role of glutathione peroxidase in apoptosis induced by reactive oxygen species. J Biochem (Tokyo) 119:817–822CrossRefGoogle Scholar
  21. Knolle PA, Limmer A (2001) Neighborhood politics: the immunoregulatory function of organ-resident liver endothelial cells. Trends Immunol 22:432–437.  https://doi.org/10.1016/S1471-4906(01)01957-3 CrossRefGoogle Scholar
  22. Kostadinova R, Boess F, Applegate D, Suter L, Weiser T, Singer T, Naughton B, Roth A (2013) A long-term three dimensional liver co-culture system for improved prediction of clinically relevant druginduced hepatotoxicity. Toxicol Appl Pharmacol 268:1–16.  https://doi.org/10.1016/j.taap.2013.01.012 CrossRefGoogle Scholar
  23. Langie SAS, Azqueta A, Collins AR (2015) The comet assay: past, present, and future. Front Genet 6:266.  https://doi.org/10.3389/fgene.2015.00266 CrossRefGoogle Scholar
  24. Li X, Zhu L, Du Z, Li B, Wang J, Wang J, Zhu Y (2018) Mesotrione-induced oxidative stress and DNA damage in earthworms (Eisenia fetida). Ecol Indic 95:436–443CrossRefGoogle Scholar
  25. Liao W, McNutt MA, Zhu WG (2009) The comet assay: a sensitive method for detecting DNA damage in individual cells. Methods 48(1):46–53.  https://doi.org/10.1016/j.ymeth.2009.02.016 CrossRefGoogle Scholar
  26. Lorenzo V, Costa S, Collins AR, Azqueta AA (2013) The comet assay, DNA damage, DNA repair and cytotoxicity: hedgehogs are not always dead. Mutagenesis 28(4):427–432.  https://doi.org/10.1093/mutage/get018 CrossRefGoogle Scholar
  27. Malik R, Selden C, Hodgson H (2002) The role of non-parenchymal cells in liver growth. Semin Cell Dev Biol 13:425–531CrossRefGoogle Scholar
  28. Mallikarjuna K, Shanmugam KR, Nishanth K, Wu MC, Hou CW, Kuo CH, Reddy KS (2010) Alcohol-induced deterioration in primary antioxidant and glutathione family enzymes reversed by exercise training in the liver of old rats. Alcohol 44:523–529.  https://doi.org/10.1016/j.alcohol.2010.07.004 CrossRefGoogle Scholar
  29. McCuskey RS (2006) Sinusoidal endothelial cells as an early target for hepatic toxicants. Clin Hemorheol Microcirc 34:5–10Google Scholar
  30. McNamee JP, Bellier PV (2015) Use of standardized JaCVAM in vitro rat comet assay protocol to assess the genotoxicity of three coded test compounds; ampicillin trihydrate, 1,2-dimethylhydrazine dihydochloride, and N-nitrosodithylamine. Mutat Res 786-788:158–164.  https://doi.org/10.1016/j.mrgentox.2015.02.005 CrossRefGoogle Scholar
  31. Medina J, Moreno-Otero R (2005) Pathophysiological basis for antioxidant therapy in chronic liver disease. Drugs 65:2445–2461.  https://doi.org/10.2165/00003495-200565170-00003 CrossRefGoogle Scholar
  32. Miyai K (1991) Structural organization of the liver. In: Meeks RG, Harrison SD, Bull RJ (eds) Hepatotoxicology. CRC Press, Boston, pp 1–65Google Scholar
  33. Moran GR (2005) 4-Hydroxyphenylpyruvate dioxygenase. Arch Biochem Biophys 433:117–128.  https://doi.org/10.1016/j.abb.2004.08.015 CrossRefGoogle Scholar
  34. Moslen MT (1996) Toxic responses of the liver. In: Klaassen CD, Amdur MO, Doull J (eds) Casarett and Doull’s Toxicology. The Basic Science of Poisons, fifth edn. McGraw-Hill, NY, pp 403–416Google Scholar
  35. Palma HE, Wolkmer P, Gallio M, Correa MM, Schmatz R, Thome GR, Pereira LB, Castro VS, Pereira AB, Bueno A, de Oliviera LS, Rosolen D, Mann TR, de Cecco BS, Grasa DL, Lopes STA (2014) Oxidative stress parameters in blood, liver, and kidney of diabetic rats treated with curcumin and/or insulin. Mol Cell Biochem 386:199–210.  https://doi.org/10.1007/s11010-013-1898-5 CrossRefGoogle Scholar
  36. Peraica M, Ljubanović D, Želježić D, Domijan A-M (2008) The effect of a single dose of fumonisin B1 on rat kidney. Croat Chem Acta 81(1):119–124 ISSN-0011-1643Google Scholar
  37. Piancini LDS, Guiloski IC, Silva de Assis HC, Cestari MM (2015) Mesotrione herbicide promotes biochemical changes and DNA damage in two fish species. Toxicol Rep 2:1157–1163.  https://doi.org/10.1016/j.toxrep.2015.08.007 CrossRefGoogle Scholar
  38. Roser S, Pool-Zobel BL, Rechkemmer G (2001) Contribution of apoptosis to responses in the comet assay. Mutat Res –Genet Toxicol Environ Mutagen 497:169–175.  https://doi.org/10.1016/S1383-5718(01)00255-8 CrossRefGoogle Scholar
  39. Sakaguchi S, Takahashi S, Sasaki T, Kumagai T, Nagata K (2011) Progression of alcoholic and non-alcoholic steatohepatitis: common metabolic aspects of innate immune system and oxidative stress. Drug Metab Pharmacokinet 26:30–46CrossRefGoogle Scholar
  40. Sellers RS, Morton D, Bindhu M, Roome N, Johnson JK, Yano BL, Perry R, Schafer K (2007) Society of Toxicologic Pathology Position paper: Organ Weight Recommendations for Toxicology Studies. Toxicol Pathol 35:751–755CrossRefGoogle Scholar
  41. Smith CC, Adkins DJ, Martin EA, O Donavan MR (2008) Recommendations for design of the rat comet assay. Mutagenesis 23(3):233–240.  https://doi.org/10.1093/mutage/gen008 CrossRefGoogle Scholar
  42. Stanger BZ (2015) Cellular homeostasis and repair in the mammalian liver. Annu Rev Physiol 77:179–200.  https://doi.org/10.1146/annurev-physiol-021113-170255 CrossRefGoogle Scholar
  43. Tice RR, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H, Miyamae Y, Rojas E, Ryu JC, Sasaki YF (2000) Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35(3):206–221CrossRefGoogle Scholar
  44. US EPA (2007) United States Environmental Protection Agency, 2007. Tembotrione. Human-health Risk Assessment for Proposed Uses on Field Corn, Sweet Corn and Popcorn. https://www.fluoridealert.org/wp-content/pesticides/EPA-HQ-OPP-2006-0072-0005.pdf
  45. Wang H, Chen X, Su Y, Paueksakon P, Hu W, Zhang MZ, Harris RC, Blackwell TS, Zent R, Pozzi A (2015) p47phox contributes to albuminuria and kidney fibrosis in mice. Kidney Int 87:948–962.  https://doi.org/10.1038/ki.2014.386 CrossRefGoogle Scholar
  46. Wang C, Harwood JD, Zhang Q (2018) Oxidative stress and DNA damage in common carp (Cyprinus carpio) exposed to the herbicide mesotrione. Chemosphere 193:1080–1086.  https://doi.org/10.1016/j.chemosphere.2017.11.148 CrossRefGoogle Scholar
  47. Zimmermann HJ (1978) Vulnerability of the liver to toxic injury. The adverse effects of drugs and other chemicals on the liver. In: Zimmermann HJ (ed) Hepatotoxicity. Appleton Century Crofts, NY, pp 32–46Google Scholar
  48. Živković Semren T, Žunec S, Pizent A (2018) Oxidative stress in triazine pesticide toxicology: a review of the main biomarker findings. Arhiv za higijenu rada I oksikologiju 69(2):109–125.  https://doi.org/10.2478/aiht-2018-69-3118 CrossRefGoogle Scholar
  49. Žunec S, Kašuba V, Pavičić I, Marjanović AM, Tariba B, Milić M, Kopjar N, Pizent A, Lucić Vrdoljak A, Rozgaj R, Želježić D (2016) Assessment of oxidative stress responses and the cytotoxic and genotoxic potential of the herbicide tembotrione in HepG2 cells. Food Chem Toxicol 94:64–74.  https://doi.org/10.1016/j.fct.2016.05.019 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Vilena Kašuba
    • 1
    Email author
  • Vedran Micek
    • 2
  • Alica Pizent
    • 3
  • Blanka Tariba Lovaković
    • 3
  • Davor Želježić
    • 1
  • Mirta Milić
    • 1
  • Nevenka Kopjar
    • 1
  1. 1.Mutagenesis UnitInstitute for Medical Research and Occupational HealthZagrebCroatia
  2. 2.Animal Breeding UnitInstitute for Medical Research and Occupational HealthZagrebCroatia
  3. 3.Analytical Toxicology and Mineral Metabolism UnitInstitute for Medical Research and Occupational HealthZagrebCroatia

Personalised recommendations