Skip to main content
SpringerLink
Log in

Disruption of cytochrome P450 enzymes in the liver and small intestine in chicken embryos in ovo exposed to glyphosate

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

Abstract

Glyphosate is the active component of several commercial formulations as in Roundup®. The present study was investigated the toxic effects of pure glyphosate or Roundup® on the liver and small intestine of chick embryos. On day 6, a total of 180 fertile eggs injected with deionized water (control group), 10 mg pure glyphosate, or 10 mg of the active ingredient glyphosate in Roundup®/kg egg mass. The results showed an increase in relative weights of the liver in embryos that treated with Roundup®. Furthermore, oxidative stress was observed in the embryos treated with glyphosate or Roundup®, increased total superoxide dismutase, and content of malondialdehyde in the liver and intestine; moreover, decrease of glutathione peroxidase in the liver with increased in the intestine compared with the control. Besides, glutamic-pyruvic transaminase was increased in Roundup® group compared with other groups. Moreover, histopathological alterations in the liver and intestine tissues were observed in treated groups. Suppression of hepatic CYP1A2, CYP1A4, CYP1B1, and MDR1 mRNA expression after exposed to Roundup®. Furthermore, inhibition of CYP1A4 in the duodenum, CYP1A4, and MRP2 in the jejunum in embryos exposed to glyphosate or Roundup®. In addition, glyphosate treatment caused an increase of CYP3A5, CYP1C1, and IFNY mRNA expression in the jejunum and CYP1A2 expression in the ileum, while IFN-Y gene increase in embryos treated with Roundup®. In conclusion, in ovo exposure to glyphosate caused histopathological alterations and induced oxidative stress in the liver and small intestines. Moreover, the expression of cytochrome P450, MDR1, and MRP2 transporters was also modulated in the liver and small intestines for chick embryos.

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
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Abass K, Turpeinen M, Pelkonen O (2009) An evaluation of the cytochrome P450 inhibition potential of selected pesticides in human hepatic microsomes. J Environ Sci Health Part B 44:553–563

    CAS  Google Scholar 

  • Abdelnour SA, Abd El-Hack ME, Alagawany M, Farag MR, Elnesr SS (2019) Beneficial impacts of bee pollen in animal production, reproduction and health. J Anim Physiol Anim Nutr 103:477–484

    Google Scholar 

  • Ahmad I, Pacheco M, Santos M (2004) Enzymatic and nonenzymatic antioxidants as an adaptation to phagocyte-induced damage in Anguilla anguilla L. following in situ harbor water exposure. Ecotoxicol Environ Saf 57:290–302

    CAS  Google Scholar 

  • Alp H et al (2016) Effects of intralipid and caffeic acid phenyl esther (CAPE) against hepatotoxicity and nephrotoxicity caused by glyphosate isopropylamine (GI). Eur J Inflamm 14:3–9

    CAS  Google Scholar 

  • Aygun A (2016) The effects of in-ovo injection of propolis on egg hatchability and starter live performance of japanese quails. Braz J Poultry Sci 18:83–89

    Google Scholar 

  • Bai SH, Ogbourne SM (2016) Glyphosate: environmental contamination, toxicity and potential risks to human health via food contamination. Environ Sci Pollut Res 23:18988–19001

    CAS  Google Scholar 

  • Benachour N, Séralini G-E (2008) Glyphosate formulations induce apoptosis and necrosis in human umbilical, embryonic, and placental cells. Chem Res Toxicol 22:97–105

    Google Scholar 

  • Benbrook CM (2016) Trends in glyphosate herbicide use in the United States and globally. Environ Sci Eur 28:3

    Google Scholar 

  • Cattani D et al (2014) Mechanisms underlying the neurotoxicity induced by glyphosate-based herbicide in immature rat hippocampus: involvement of glutamate excitotoxicity. Toxicology 320:34–45

    CAS  Google Scholar 

  • Çavuşoğlu K, Yapar K, Oruc E, Yalçın E (2011) Protective effect of Ginkgo biloba L. leaf extract against glyphosate toxicity in Swiss albino mice. J Med Food 14:1263–1272

    Google Scholar 

  • Chan LM, Lowes S, Hirst BH (2004) The ABCs of drug transport in intestine and liver: efflux proteins limiting drug absorption and bioavailability. Eur J Pharm Sci 21:25–51

    CAS  Google Scholar 

  • Cupp MJ, Tracy TS (1998) Cytochrome P450: new nomenclature and clinical implications. Am Fam Physician 57:107–116

    CAS  Google Scholar 

  • Diaz G, Murcia H, Cepeda S (2010) Bioactivation of aflatoxin B1 by turkey liver microsomes: responsible cytochrome P450 enzymes. Br Poult Sci 51:828–837

    CAS  Google Scholar 

  • Duca RC, Mabondzo A, Bravin F, Delaforge M (2012) In vivo effects of zearalenone on the expression of proteins involved in the detoxification of rat xenobiotics. Environ Toxicol 27:98–108

    CAS  Google Scholar 

  • EFSA (2016) The 2014 European Union report on pesticide residues in food. EFSA J 14:e04611

    Google Scholar 

  • Elie-Caille C, Heu C, Guyon C, Nicod L (2010) Morphological damages of a glyphosate-treated human keratinocyte cell line revealed by a micro-to nanoscale microscopic investigation. Cell Biol Toxicol 26:331–339

    CAS  Google Scholar 

  • El-Kholy MS, Ibrahim ZAEG, El-Mekkawy MM, Alagawany M (2019) Influence of in ovo administration of some water-soluble vitamins on hatchability traits, growth, carcass traits and blood chemistry of Japanese quails. Ann Anim Sci 19:97–111

    CAS  Google Scholar 

  • Elnesr S, Elwan H, Xu Q, Xie C, Dong X, Zou X (2019) Effects of in ovo injection of sulfur-containing amino acids on heat shock protein 70, corticosterone hormone, antioxidant indices, and lipid profile of newly hatched broiler chicks exposed to heat stress during incubation. Poult Sci 98:2290–2298

    CAS  Google Scholar 

  • El-Shenawy NS (2009) Oxidative stress responses of rats exposed to Roundup and its active ingredient glyphosate. Environ Toxicol Pharmacol 28:379–385

    CAS  Google Scholar 

  • Elwan HA, Elnesr SS, Xu Q, Xie C, Dong X, Zou X (2019) Effects of in ovo methionine-cysteine injection on embryonic development, antioxidant status, IGF-I and TLR4 gene expression, and jejunum histomorphometry in newly hatched broiler chicks exposed to heat stress during incubation. Animals 9:25

    Google Scholar 

  • EPA U (1993) Re-registration eligibility decision (RED): glyphosate. EPA 738-R-93-014. US Environmental Protection Agency, Office of Pesticide Programs and Toxic Substances, Washington, DC

  • Fathi MA et al (2019) Effect of in ovo glyphosate injection on embryonic development, serum biochemistry, antioxidant status and histopathological changes in newly hatched chicks. J Anim Physiol Anim Nutr 103:1776–1784

    CAS  Google Scholar 

  • Frye RF, Zgheib NK, Matzke GR, Chaves-Gnecco D, Rabinovitz M, Shaikh OS, Branch RA (2006) Liver disease selectively modulates cytochrome P450–mediated metabolism. Clin Pharmacol Ther 80:235–245

    CAS  Google Scholar 

  • Gasnier C, Dumont C, Benachour N, Clair E, Chagnon M-C, Séralini G-E (2009) Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines. Toxicology 262:184–191

    CAS  Google Scholar 

  • Ghareeb K, Awad WA, Soodoi C, Sasgary S, Strasser A, Böhm J (2013) Effects of feed contaminant deoxynivalenol on plasma cytokines and mRNA expression of immune genes in the intestine of broiler chickens. PLoS One 8:e71492

    CAS  Google Scholar 

  • Guo M, Sun Y, Zhang Y, Bughio S, Dai X, Ren W, Wang L (2014) E. coli infection modulates the pharmacokinetics of oral enrofloxacin by targeting P-glycoprotein in small intestine and CYP450 3A in liver and kidney of broilers. PLoS One 9:e87781

    Google Scholar 

  • Hershko C, Patz J (2008) Ironing out the mechanism of anemia in celiac disease. Haematologica 93(12):1761–1765

  • Hodgson E (2003) In vitro human phase I metabolism of xenobiotics I: pesticides and related compounds used in agriculture and public health, May 2003. J Biochem Mol Toxicol 17:201–206

    CAS  Google Scholar 

  • Kalpana S, Rao GS, Malik JK (2015) Impact of aflatoxin B1 on the pharmacokinetic disposition of enrofloxacin in broiler chickens. Environ Toxicol Pharmacol 40:645–649

    CAS  Google Scholar 

  • Larsen K, Najle R, Lifschitz A, Virkel G (2012) Effects of sub-lethal exposure of rats to the herbicide glyphosate in drinking water: glutathione transferase enzyme activities, levels of reduced glutathione and lipid peroxidation in liver, kidneys and small intestine. Environ Toxicol Pharmacol 34:811–818

    CAS  Google Scholar 

  • Larsen K, Najle R, Lifschitz A, Maté ML, Lanusse C, Virkel GL (2014) Effects of sublethal exposure to a glyphosate-based herbicide formulation on metabolic activities of different xenobiotic-metabolizing enzymes in rats. Int J Toxicol 33:307–318

    CAS  Google Scholar 

  • Linton KJ (2007) Structure and function of ABC transporters. Physiology 22:122–130

    CAS  Google Scholar 

  • Liu M, Gao R, Meng Q, Zhang Y, Bi C, Shan A (2014) Toxic effects of maternal zearalenone exposure on intestinal oxidative stress, barrier function, immunological and morphological changes in rats. PLoS One 9:e106412

    Google Scholar 

  • Marin DE, Taranu I (2012) Overview on aflatoxins and oxidative stress. Toxin Rev 31:32–43

    CAS  Google Scholar 

  • Mary VS, Valdehita A, Navas JM, Rubinstein HR, Fernández-Cruz ML (2015) Effects of aflatoxin B1, fumonisin B1 and their mixture on the aryl hydrocarbon receptor and cytochrome P450 1A induction. Food Chem Toxicol 75:104–111

    CAS  Google Scholar 

  • Mesnage R, Séralini GÉ (2014) The need for a closer look at pesticide toxicity during GMO assessment. In: Bhat R, Gómez-López VM (eds) Practical food safety: contemporary issues and future directions. John Wiley & Sons, Ltd., Chichester, pp 167–189

  • Milić M et al (2018) Oxidative stress, cholinesterase activity, and DNA damage in the liver, whole blood, and plasma of Wistar rats following a 28-day exposure to glyphosate. Arch Ind Hyg Toxicol 69:154–168

    Google Scholar 

  • Mottier A, Kientz-Bouchart V, Serpentini A, Lebel JM, Jha AN, Costil K (2013) Effects of glyphosate-based herbicides on embryo-larval development and metamorphosis in the Pacific oyster, Crassostrea gigas. Aquat Toxicol 128:67–78

    Google Scholar 

  • Nielsen LN et al (2018) Glyphosate has limited short-term effects on commensal bacterial community composition in the gut environment due to sufficient aromatic amino acid levels. Environ Pollut 233:364–376

    CAS  Google Scholar 

  • Olaleye SB, Adaramoye OA, Erigbali PP, Adeniyi OS (2007) Lead exposure increases oxidative stress in the gastric mucosa of HCl/ethanol-exposed rats. World J Gastroenterol: WJG 13:5121

    CAS  Google Scholar 

  • Osselaere A, Li SJ, de Bock L, Devreese M, Goossens J, Vandenbroucke V, van Bocxlaer J, Boussery K, Pasmans F, Martel A, de Backer P, Croubels S (2013) Toxic effects of dietary exposure to T-2 toxin on intestinal and hepatic biotransformation enzymes and drug transporter systems in broiler chickens. Food Chem Toxicol 55:150–155

    CAS  Google Scholar 

  • Ozden S, Alpertunga B (2010) Effects of methiocarb on lipid peroxidation and glutathione level in rat tissues. Drug Chem Toxicol 33:50–54

    CAS  Google Scholar 

  • Paganelli A, Gnazzo V, Acosta H, López SL, Carrasco AE (2010) Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signaling. Chem Res Toxicol 23:1586–1595

    CAS  Google Scholar 

  • Ray WJ, Bain G, Yao M, Gottlieb DI (1997) CYP26, a novel mammalian cytochrome P450, is induced by retinoic acid and defines a new family. J Biol Chem 272:18702–18708

    CAS  Google Scholar 

  • Ren X et al (2019) Effects of chronic glyphosate exposure to pregnant mice on hepatic lipid metabolism in offspring. Environ Pollut 254:112906

    CAS  Google Scholar 

  • Richard S, Moslemi S, Sipahutar H, Benachour N, Seralini G-E (2005) Differential effects of glyphosate and roundup on human placental cells and aromatase. Environ Health Perspect 113:716–720

    CAS  Google Scholar 

  • Romano RM, Romano MA, Bernardi MM, Furtado P, Oliveira CAD (2010) Prepubertal exposure to commercial formulation of the herbicide glyphosate alters testosterone levels and testicular morphology. Arch Toxicol 84:309–317

    CAS  Google Scholar 

  • Saeed M et al (2019) In ovo delivery of various biological supplements, vaccines and drugs in poultry: current knowledge. J Sci Food Agric 99:3727–3739

    CAS  Google Scholar 

  • Sakamoto K, Hirose H, Onizuka A, Hayashi M, Futamura N, Kawamura Y, Ezaki T (2000) Quantitative study of changes in intestinal morphology and mucus gel on total parenteral nutrition in rats. J Surg Res 94:99–106

    CAS  Google Scholar 

  • Samanta P, Pal S, Mukherjee A, Ghosh A (2016) Pathological (histological and ultrastructural) study in stomach and intestine of Heteropneustes fossilis (Bloch) to excel Mera 71, a glyphosate-based herbicide. J Gastrointest Dig Syst 6:2

    Google Scholar 

  • Samsel A, Seneff S (2013) Glyphosate’s suppression of cytochrome P450 enzymes and amino acid biosynthesis by the gut microbiome: pathways to modern diseases. Entropy 15:1416–1463

    CAS  Google Scholar 

  • Sharma J, Burmester B (1982) Resistance of Marek’s disease at hatching in chickens vaccinated as embryos with the Turkey herpesvirus. Avian Dis 26(1):134–149

  • Sharma P, Dubey R (2007) Involvement of oxidative stress and role of antioxidative defense system in growing rice seedlings exposed to toxic concentrations of aluminum. Plant Cell Rep 26:2027–2038

    CAS  Google Scholar 

  • Taimi M, Helvig C, Wisniewski J, Ramshaw H, White J, Korczak B, Petkovich M (2004) A novel human cytochrome P450, CYP26C1, involved in metabolism of 9-cis and all-trans isomers of retinoic acid. J Biol Chem 279:77–85

    CAS  Google Scholar 

  • Tang J, Hu P, Li Y, Win-Shwe T-T, Li C (2017) Ion imbalance is involved in the mechanisms of liver oxidative damage in rats exposed to glyphosate. Front Physiol 8:1083

    Google Scholar 

  • Torretta V, Katsoyiannis I, Viotti P, Rada E (2018) Critical review of the effects of glyphosate exposure to the environment and humans through the food supply chain. Sustainability 10:950

    Google Scholar 

  • Turkmen R, Birdane YO, Demirel HH, Yavuz H, Kabu M, Ince S (2019) Antioxidant and cytoprotective effects of N-acetylcysteine against subchronic oral glyphosate-based herbicide-induced oxidative stress in rats. Environ Sci Pollut Res 26:11427–11437

    CAS  Google Scholar 

  • Yoda N, Emoto C, Date S, Kondo S, Miyake M, Nakazato S, Umehara K, Kashiyama E (2012) Characterization of intestinal and hepatic P450 enzymes in cynomolgus monkeys with typical substrates and inhibitors for human P450 enzymes. Xenobiotica 42:719–730

    Google Scholar 

  • Yuan Y, Zhou X, Yang J, Li M, Qiu X (2013) T-2 toxin is hydroxylated by chicken CYP3A37. Food Chem Toxicol 62:622–627

    CAS  Google Scholar 

  • Yun Y, Gao T, Li Y, Gao Z, Duan J, Yin H, Duan W (2016) Excretory function of intestinal tract enhanced in kidney impaired rats caused by adenine. Sci World J 16:2695718

  • Zhang Y, Benet LZ (2001) The gut as a barrier to drug absorption. Clin Pharmacokinet 40:159–168

    CAS  Google Scholar 

  • Zhang J, Li C, Tang X, Lu Q, Sa R, Zhang H (2015) Proteome changes in the small intestinal mucosa of broilers (Gallus gallus) induced by high concentrations of atmospheric ammonia. Proteome Sci 13:9

    Google Scholar 

  • Zhang N-Y et al (2016) Curcumin prevents aflatoxin B1 hepatoxicity by inhibition of cytochrome P450 isozymes in chick liver. Toxins 8:327

    Google Scholar 

  • Zhao J, Pacenka S, Wu J, Richards BK, Steenhuis T, Simpson K, Hay AG (2018) Detection of glyphosate residues in companion animal feeds. Environ Pollut 243:1113–1118

    CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Nature Science Foundation of China (No. 31772648).

Author information

Authors and Affiliations

  1. Animal Science and Technology, Nanjing Agricultural University, No.1 Weigang, Nanjing, 210095, Jiangsu, People’s Republic of China

    Mohamed Ahmed Fathi, Guofeng Han, Ruifen Kang, Dan Shen, Jiakun Shen & Chunmei Li

  2. Animal Production Research Institute, Agriculture Research Centre, Dokki, Giza, 12618, Egypt

    Mohamed Ahmed Fathi

Authors
  1. Mohamed Ahmed Fathi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guofeng Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ruifen Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dan Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jiakun Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chunmei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chunmei Li.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Responsible Editor: Lotfi Aleya

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fathi, M.A., Han, G., Kang, R. et al. Disruption of cytochrome P450 enzymes in the liver and small intestine in chicken embryos in ovo exposed to glyphosate. Environ Sci Pollut Res 27, 16865–16875 (2020). https://doi.org/10.1007/s11356-020-08269-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-020-08269-3

Keywords

Search

Navigation