Comparative studies on endogenic stress hormones, antioxidant, biochemical and hematological status of metabolic disturbance in albino rat exposed to roundup herbicide and its active ingredient glyphosate

  • Folarin OwagboriayeEmail author
  • Gabriel Dedeke
  • Kehinde Ademolu
  • Olanrewaju Olujimi
  • Adeyinka Aladesida
  • Mistura Adeleke
Research Article


There have been growing concerns and uncertainty about reports attributing the metabolic disturbance induced by a commercial formulation of glyphosate-based herbicide to its active ingredient. We therefore compared the effects of Roundup Original® and its active ingredient glyphosate on some hypothalamic-pituitary-adrenal (HPA) hormones and oxidative stress markers, biochemical and hematological profiles in 56 adult male albino rats randomly assigned to seven treatments of eight rats per treatment. The rats were orally exposed to Roundup Original® and its active ingredient daily at 3.6 mg/kg body weight (bw), 50.4 and 248.4 mg/kgbw of glyphosate equivalent concentrations for 12 weeks, while control treatment received distilled water. Serum concentrations of corticosterone, adrenocorticotropic hormone, aldosterone and concentration of oxidative stress marker, biochemical and hematological profiles in the blood were determined. Concentrations of corticosterone and aldosterone were significantly higher (p < 0.05) in rats treated with Roundup in a dose-dependent manner. Reduced glutathione concentration, catalase, and butyrylcholinesterase activities reduced significantly in rats treated with Roundup relative to those treated with the active ingredient. Lipid peroxidation was observed in rats treated with Roundup. Biochemical and hematological profiles of rats treated with Roundup were significantly altered (p < 0.05). However, significant changes in only acid phosphatase, lactase dehydrogenase, bilirubin, and white blood cells in rats treated with the active ingredient at 50.4 mg/kg were observed. The severe metabolic disturbance and stress observed in rats treated with the commercial formulation of Roundup herbicide may not be associated with the mild changes induced by the active ingredient.


Glyphosate Herbicide Environmental pollution Metabolism Oxidative stress Adrenal hormone 



Department of Zoology and Environmental Biology, Faculty of Science, Olabisi Onabanjo University permitted us to use its facilities. We also appreciate the technical assistance of laboratory technologist in the central biotechnology laboratory of the Federal University of Agriculture Abeokuta, University of Lagos and Olabisi Onabanjo University Ago-Iwoye, Nigeria.

Author roles

The experiment was conceived by FO and GD; designed by FO, GD, KA, and OO; and performed by FO and MA. Analysis of data and results interpretation was done by FO and AA. The manuscript was drafted by FO and revised by all the authors before final approval was given.

Funding information

We received financial support for this study through the 2013 needs assessment special presidential intervention fund in public Universities.

Compliance with ethical standards

We conducted the experimental protocol according to the regulations of the local ethics committee in animal care unit of our universities. Ethical guidelines of animal experimentation (regulation CEE 86/609) were followed in performing the animal study.

Conflict of interest

The authors declare no competing interest in this research.


  1. Ahmad I, Pacheco M, Santos MA (2004) Enzymatic antioxidants as an adaptation to phagocytes induced damage in Anguilla anguilla L. following in situ harbor water exposure. Ecotoxicol Environ Saf 57:290–295CrossRefGoogle Scholar
  2. Antinio MT, Corredor L, Leret ML (2003) Study of the toxicity of several brain enzymes-like markers of neurotoxicity induced by prenatural exposure to lead and/or cadmium. Toxicol Lett 143:331–340CrossRefGoogle Scholar
  3. Antoniou M, Habib MEM, Howard CV, Jennings RC, Leifert C, Nodari RO (2012) Teratogenic effects of glyphosate-based herbicides: divergence of regulatory decisions from scientific evidence. J Environ Anal Toxicol S4:006. Google Scholar
  4. Antonov EV, Markel AL, Yakobson GS (2011) Aldosterone and stress-dependent arterial hypertension. Bull Exp Biol Med 152(2):188–191CrossRefGoogle Scholar
  5. Bai H, Liu R, Chen HL, Zhang W, Wang X, Zhang XD (2014) Enhanced antioxidant effect of caffeic acid phenethyl ester and Trolox in combination against radiation induced-oxidative stress. Chem Biol Interact 207:7–15CrossRefGoogle Scholar
  6. Barcellos LJG, Kreutz LC, Rodrigues LB, Fioreze I, Quevedo RM, Cericato L, Conrad J, Soso AB, Fagundes M, Lacerda LA, Terra S (2003) Haematological and biochemical characteristics of male jundia (Rhamdia Quelen, Quoy & GaimaRDT, Pimelodidae): changes after acute stress. Aquac Res 34:1465–1469CrossRefGoogle Scholar
  7. Barzilai A, Yamamoto KI (2004) DNA damage responses to oxidative stress. DNA Repair 3:1109–1115CrossRefGoogle Scholar
  8. Benedetti AL, de Vituri L, Trentin AG, Domingues MA, Alvarez-Silva M (2004) The effects of sub-chronic exposure of Wistar rats to the herbicide Glyphosate-Biocarb. Toxicol Lett 153:227–232CrossRefGoogle Scholar
  9. Bohn T, Cuhra M, Traavik T, Sanden M, Fagan J, Primicerio R (2013) Compositional differences in soybeans on the market: glyphosate accumulates in Roundup Ready GM soybeans. Food Chem 153:207–215CrossRefGoogle Scholar
  10. Bradberry SE, Proudfoot AT, Vale JA, (2004) Glyphosate poisoning. Toxicol Rev 23(3):159–167Google Scholar
  11. Brausch JM, Smith PN (2007) Toxicity of three polyethoxylated tallowamine surfactant formulations to laboratory and field collected fairy shrimp Thamnocephalus platyurus. Arch Environ Contam Toxicol 52(2):217–221CrossRefGoogle Scholar
  12. Castellanos-Sinco HB, Sinco-Angeles A (2015) Megaloblastic anemia: folic acid and vitamin B-12 metabolism. Rev Med Del Hosp Gen Mex 78(3):135–143Google Scholar
  13. Cerdeira AL, Gazziero DLP, Duke SO, Matallo MB, Spadotto CA (2007) Review of potential environmental impacts of transgenic glyphosate-resistant soybean in Brazil. J Environ Sci Health B 42:539–549CrossRefGoogle Scholar
  14. De Kloet ER, Rinne T (2007) Neuroendocrine markers of early trauma: implications for posttraumatic stress disorder. In: Vermetten E, Dorahy MJ, Spiegel D (eds) Traumatic dissociation: neurobiology and treatment. American Psychiatric Press, Washington, DCGoogle Scholar
  15. De Liz O, Cavalli VL, Cattani D, Heinz Rieg CE, Pierozan P, Zanatta L (2013) Roundup disrupted male reproductive functions by triggering calcium-mediated cell death in rat testis and sertoli cells. Free Radic Biol Med 65:335–346CrossRefGoogle Scholar
  16. De Moura FR, da Silva L, Ritane R, da Costa M, Patricia A, Danilo H, Sugui MM, Sinhorin APS, Valeria DG (2017) Effects of glyphosate-based herbicide on pintado da Amazonia: hematology, histological aspects, metabolic parameters and genotoxic potential. Environ Toxicol Pharmacol.
  17. EFSA (2014) The 2011 European Union report on pesticide residues in food. EFSA J 12:36–94Google Scholar
  18. Ellman GL, Coutney KD, Anders VJR, Feartherstone RM (1961) A new rapid colorimetric determination of acetyl cholinesterase activity. Biochem Pharmacol 7:88–95CrossRefGoogle Scholar
  19. El-Shenawy NS (2009) Oxidative stress responses of rats exposed to roundup and its active ingredient glyphosate. Environ Toxicol Phamacol 28:379–385CrossRefGoogle Scholar
  20. FAO/WHO Joint Meeting on Pesticide Residues. Evaluation of glyphosate (158) (2005) Available at Accessed 17 Oct 2018
  21. Franklin TB, Saab BJ, Mansuy IM (2012) Neural mechanisms of stress resilience and vulnerability. Neuron 75(5):747–761CrossRefGoogle Scholar
  22. Franz JE, Mao MK, Sikorski JA (1997) Glyphosate: A unique global herbicide. Am Chem Soc 189:163–175Google Scholar
  23. Friends of the Earth Europe (FEE) (2013) Human contamination by glyphosate. Brussels, Belgium, pp 1–12Google Scholar
  24. Giesy J, Dobson S, Solomon K (2000) Ecotoxicological risk assessment for Roundup® herbicide. Environ Contam Toxicol 167:35–120Google Scholar
  25. Glusczak L, Miron DS, Moraes BS, Simões RR, Schetinger MR, Morsch VM, Loro VL (2007) Acutte effects of glyphosate herbicide on metabolic and enzymatic parameters of silver catfish (Rhamdia quelen). Comp Biochem Physiol C Toxicol Pharmacol 46(4):519–524CrossRefGoogle Scholar
  26. Harish RS, Murugan K (2011) Oxidative stress indices in natural populations of Avicennia alba Blume as biomarker of environmental pollution. Environ Res 11(8):1070–1073CrossRefGoogle Scholar
  27. Hassan AM, Barakat AH (2008) Assessment of oxidative stress induced by nickel chloride and antioxidant effects of basil (Ocimum basilicum L.) and thyme (Thymus vulgaris L.). J Genet Eng Biotechnol 6(2):29–38Google Scholar
  28. Hill MF, Singal PK (1996) Antioxidant and oxidative stress changes during heart failure subsequent to myocardial infarction in rats. Am J Pathol 148:291–293Google Scholar
  29. Horffebrand AV (2012) Chapter 105. Megaloblastic Anemias. In: Longo DL, Francis AS, Kasper DL, Hauber SL (eds) Harrison’s Principles of Internal Medicine, 18th edn. McGraw-Hill, New YorkGoogle Scholar
  30. Howe CM, Berrill M, Pauli DB, Helbing CC, Werr K, Veldhoen N (2004) Toxicity of glyphosate-based pesticides to four North American frog species. Environ Toxicol Chem 23:1928–1938CrossRefGoogle Scholar
  31. Jacobson L (2005) Hypothalamic-pituitary-adrenocortical axis regulation. Endocrinol Metab Clin N Am 34:271–292CrossRefGoogle Scholar
  32. Jasper R, Locatelli GO, Pilati C, Locatelli C (2012) Evaluation of biochemical, haematological and oxidative parameters in mice exposed to the herbicide glyphosate-Roundup®. Interdiscip Toxicol 5(3):133–140CrossRefGoogle Scholar
  33. Jessica LM, Wendy S, Fernando RG, Enrico LR, Daniel RJ, Theodore G (2006) Baseline and stress-induced plasma corticosterone concentrations of mice selectively bred for high voluntary wheel running. Physiol Biochem Zool 80(1):146–156Google Scholar
  34. Johansson LH, Borg LAH (1979) Aspectrophotomertic method for determination of catalase activity in small tissue samples. Anal Biochem 174:331–336CrossRefGoogle Scholar
  35. Johnson AK, Grippo AJ (2006) Sadness and broken hearts: neurohumoral mechanisms and co morbidity of ischemic heart disease and psychological depression. J Physiol Pharmacol 57(Suppl 11):5–29Google Scholar
  36. Jovanovic T, Phifer JE, Sicking K, Weiss T, Norrholm SD, Bradley B, Ressler KJ (2011) Cortisol suppression by dexamethasone reduces exaggerated fear responses in posttraumatic stress disorder. Psychoneuroendocrinology 36:1540–1552CrossRefGoogle Scholar
  37. Larini L (1999) In: Manole (ed) Toxicologia dos Praguicidas pp 178–179Google Scholar
  38. Mesnage R, Antoniou MN (2017) Facts and fallacies in the debate on glyphosate toxicity. Front Public Health 5:316. CrossRefGoogle Scholar
  39. Mesnage R, Antoniou MN (2018) Ignoring adjuvant toxicity falsifies the safety profile of commercial pesticides. Front Public Health 5:361CrossRefGoogle Scholar
  40. Mesnage R, Moesch C, Le Grand R, Lauthier G, de Vendomois JS, Gress S, Se’ralini GE (2012) Glyphosate exposure in a farmer’s family. J Environ Prot 23:1001–1003CrossRefGoogle Scholar
  41. Mesnage R, Bernay B, Séralini GE (2013) Ethoxylated adjuvants of glyphosate-based herbicides are active principles of human cell toxicity. Toxicology 313:122–128CrossRefGoogle Scholar
  42. Mesnage R, Defarge N, Spiroux de Vendômois J, Séralini GE (2014) Major pesticides are more toxic to human cells than their declared active principles. Biomed Res Int 2014:179691CrossRefGoogle Scholar
  43. Mesnage R, Arno M, Costanzo M, Malatesta M, Séralini GE, Antoniou MN (2015a) Transcriptome profile analysis reflects rat liver and kidney damage following chronic ultra-low dose Roundup exposure. Environ Health 14:70–75CrossRefGoogle Scholar
  44. Mesnage R, Defarge N, Spiroux de Vendomois J, Seralini GE (2015b) Potential toxic effects of glyphosate and its commercial formulations below regulatory limits. Food Chem Toxicol 84:133–153CrossRefGoogle Scholar
  45. Mesnage R, Renney G, Séralini GE, Ward M, Antoniou MN (2017) Multiomics reveal non-alcoholic fatty liver disease in rats following chronic exposure to an ultra-low dose of Roundup herbicide. Sci Rep 7:39328CrossRefGoogle Scholar
  46. Miller AM, Harley JP (1996) Zoology. Wm. C. Brown Publishers, DubuqueGoogle Scholar
  47. Monsanto International and Monsanto Europe (2010) The agronomic benefits of glyphosate in Europe- benefits of glyphosate per market use. REVIEW p 1–82Google Scholar
  48. Murrey RK, Granner DK, Roduell VW (2006) Harper’s illustrated biochemistry, 27th edn. Mc Graw Hill Comp Inc, BostonGoogle Scholar
  49. Nabil MI, Esarri AE, Hossan SE, Yasmin EA (2012) Effect of lead acetate toxicity on experimental male albino rat. Asian Pac J Trop Biomed 2(1):41–46CrossRefGoogle Scholar
  50. Neil RC (2004) Physiology of behaviour. Pearson Education Inc. U.S.AGoogle Scholar
  51. Neiva TJC, Moraes ACR, Schwyzer R, Rocha TRF, Fries DM, Silva AM, Benedetti AL (2010) In vitro effect of the herbicide glyphosate on human blood platelet aggregation and coagulation. Rev Bras Hematol Hemoter 32(4):291–294CrossRefGoogle Scholar
  52. Nordberg A, Ballard C, Bullock R, Darreh-Shori T, Somogyi M (2013) A review of butyrylcholinesterase as a therapeutic target in the treatment of Alzheimer’s disease. Prim Care Companion CNS Disord 15(2)Google Scholar
  53. Odewabi AO, Ogundahunsi OA, Oyalowo M (2014) Effect of exposure to petroleum fumes on plasma antioxidant defense system in petrol attendants. Br J Pharmacol Toxicol 5(2):83–87Google Scholar
  54. Okhawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358CrossRefGoogle Scholar
  55. Owagboriaye FO, Dedeke GA, Aladesida AA, Bamidele JA, Olooto WE (2016) Assessment of the effect of gasoline fume on stress hormones, antioxidant status and lipid peroxidation in albino rat. J King Saud Uni Sci.
  56. Owagboriaye FO, Dedeke GA, Ademolu KO, Olujimi OO, Ashidi JS, Aladesida AA (2017) Reproductive toxicity of Roundup herbicide exposure in male albino rat. Exp Toxicol Pathol 69:461–468CrossRefGoogle Scholar
  57. Owagboriaye FO, Dedeke GA, Ashidi JS, Aladesida AA, Olooto WE (2018) Effect of gasoline fumes on reproductive function in male albino rats. Environ Sci Pollut Res 25:4309–4319CrossRefGoogle Scholar
  58. Pandey A, Rudraiah M (2015) Analysis of endocrine disruption effect of Roundup® in adrenal gland of male rats. Toxicol Rep 2:1075–1085CrossRefGoogle Scholar
  59. Pastore A, Piemonte F, Locatelli M, Russo AL, Gaeta LM, Tozzi G, Federici G (2003) Determination of blood total, reduced, and oxidized glutathione in pediatric subjects. Clin Chem 47(8):1467–1469Google Scholar
  60. Romano RM, Romano MA, Bernardi MM, Furtado PV, Oliveira CA (2010) Prepubertal exposure to commercial formulation of the herbicide glyphosate alters testosterone levels and testicular morphology. Arch Toxicol 84:309–317CrossRefGoogle Scholar
  61. Saddik L, Bah TM, Aoues A, Braderdour M, Silmani M (2010) Dried leaf extract protects against lead-induced neurotoxicity in Wistar rats. Eur J Sci Res 42(1):139–151Google Scholar
  62. Sánchez JAA, Varela Junior AS, Corcini CD, da Silva JC, Primel EG, Caldas S, Klein RD, Martins CDMG (2017) Effects of Roundup formulations on biochemical biomarkers and male sperm quality of the livebearing Jenynsia multidentata. Chemosphere 177:200–210. CrossRefGoogle Scholar
  63. Scandalios JG (2005) Oxidative stress: molecular perception and transduction of signals triggering antioxidant gene defenses. Braz J Med Biol Res 38:995–1014CrossRefGoogle Scholar
  64. Williams GM, Kroes R, Munro IC (2000) Safety evaluation and risk assessment of the herbicide Roundup and its active ingredient, glyphosate, for humans. Regul Toxicol Pharmacol 31:117–165CrossRefGoogle Scholar
  65. Yang Y, Ma H (2009) Aldosterone. Researcher 1(5):89–93Google Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Department of Zoology and Environmental Biology, Faculty of ScienceOlabisi Onabanjo University Ago-IwoyeAgo-IwoyeNigeria
  2. 2.Department of Pure and Applied Zoology, College of BioscienceFederal University of AgricultureAbeokutaNigeria
  3. 3.Department of Environmental Management and Toxicology, College of Environmental ManagementFederal University of AgricultureAbeokutaNigeria

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