Skip to main content
SpringerLink
Log in

Glycyrrhizic acid modulates the atrazine-induced apoptosis in rabbit spleen

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

Abstract

Atrazine (ATR) is a common herbicide used worldwide. It is a potent endocrine disruptor that causes hormonal imbalance. We investigated the modulatory role predisposed by glycyrrhizic acid (GA) against the hazardous effects caused by the ATR in the rabbit spleen. Sixty rabbits were assigned into 4 groups. The first group is the negative control; the ATR group received 1/10 of the oral LD 50 ATR; the GA group received 50 mg/kg body weight daily intraproteinally; and group 4 received both ATR and GA concurrently. ATR and GA administrations were done for 60 days. ATR-induced humoral immunotoxicity was illustrated by decreased serum total protein, albumin, and globulin levels and rabbit hemorrhagic disease virus antibody titer, 4 weeks after vaccination. Moreover, upregulation of spleen Fas and caspase-III genes was recorded in ATR-exposed rabbits. Clear splenocyte apoptosis was observed in the immunohistochemical examination by the caspase-III technique. GA diminished the ATR-induced splenocyte apoptosis through downregulation of Fas and caspase-III expressions. In conclusion, our findings bounced a new perspective into the mechanism by which ATR induces immunotoxicity and assumed the potential modulatory role of GA.

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

  • Abd El-Twab SM, Hozayen WG, Hussein OE, Mahmoud AM (2016) 18β-Glycyrrhetinic acid protects against methotrexate-induced kidney injury by up-regulating the Nrf2/ARE/HO-1 pathway and endogenous antioxidants. Ren Fail 38(9):1516–1527

    Article  CAS  Google Scholar 

  • Abdel Aziz RL, Abdel-Wahab A, Abo El-Ela F, Hassan NE, El-Nahass ES, Ibrahim MA, Khalil AA (2018) Dose-dependent ameliorative effects of quercetin and l-carnitine against atrazine-induced reproductive toxicity in adult male Albino rats. Biomed Pharmacother 102:855–864

    Article  CAS  Google Scholar 

  • Asl MN, Hosseinzadeh H (2008) Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phytother Res 22:709–724

    Article  CAS  Google Scholar 

  • Bancroft JD, Gamble M (2008) Theory and practice of histological techniques, 6th edn. Churchill Livingstone, Philadelphia, pp 473–491

    Google Scholar 

  • Bancroft JD, Stevans A, Turner DR (1996) Theory and practice of histopathological techniques, 4th edn. Churchill Livingstone, Edinburgh

    Google Scholar 

  • Boffetta P, Adami HO, Berry SC, Mandel JS (2013) Atrazine and cancer: a review of the epidemiologic evidence. Eur J Cancer Prev 22:169–180

    Article  CAS  Google Scholar 

  • Bordbar N, Karimi MH, Amirghofran Z (2012) The effect of glycyrrhizin on maturation and T cell stimulating activity of dendritic cells. Cell Immunol 280(1):44–49

    Article  CAS  Google Scholar 

  • Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516

    Article  CAS  Google Scholar 

  • Filipov NM, Pinchuk LM, Boyd BL, Crittenden PL (2005) Immunotoxic effects of short-term atrazine exposure in young male C57BL/6 mice. Toxicol Sci 86:324–332

    Article  CAS  Google Scholar 

  • Gao, S.; Wang, Z.; Zhang, C.; Jia, L. and Zhang, Y. (2016). Oral exposure to atrazine induces oxidative stress and calcium homeostasis disruption in spleen of mice. Oxid Med Cell Longev 1–9

    Article  CAS  Google Scholar 

  • Hussain R, Mahmood F, Khan A, Javed MT, Rehan S, Mehdi T (2012) Cellular and biochemical effects induced by atrazine on blood of male Japanese quail (Coturnix japonica). Pestic Biochem Physiol 103:38–42

    Article  CAS  Google Scholar 

  • Jia X, Wang D, Gao N, Cao H, Zhang H (2015) Atrazine triggers the extrinsic apoptosis pathway in lymphocytes of the frog Pelophylax nigromaculata in vivo. Chem Res Toxicol 28(10):2010–2018

    Article  CAS  Google Scholar 

  • Kamel S, Ibrahim MA, Awad ET, El-Hindi HMA, Abdel-Aziz SA (2018) Molecular cloning and characterization of the novel CYP2J2 in dromedary camels (Camelus dromedarius). Int J Biol Macromol 120(Pt B):1770–1776

    Article  CAS  Google Scholar 

  • Khalaf AA, Ahmed W, Moselhy WA, Abdel-Halim BR, Ibrahim MA (2019) Protective effects of selenium and nano-selenium on bisphenol-induced reproductive toxicity in male rats. Hum Exp Toxicol 38(4):398–408

    Article  CAS  Google Scholar 

  • Kuroda N, Inoue K, Ikeda T, Hara Y, Wake K, Sato T (2014) Apoptotic response through a high mobility box 1 protein-dependent mechanism in LPS/GalN-induced mouse liver failure and glycyrrhizin-mediated inhibition. PLoS One 9(4):e92884

    Article  CAS  Google Scholar 

  • Lavrik IN, Krammer PH (2012) Regulation of CD95/Fas signaling at the DISC. Cell Death Differ 19:36–41

    Article  CAS  Google Scholar 

  • Lee E, Jang Y, Kang K, Song D, Kim R, Chang H, Lee DE, Song CK, Choi B, Kang M, Chang E (2014) Atrazine induces endoplasmic reticulum stress-mediated apoptosis of T lymphocytes via the caspase-8-dependent pathway. Environ Toxicol 31(8):998–1008

    Article  CAS  Google Scholar 

  • Lin S, Chu P, Liao W, Wu M, Tsui K, Lin L, Huang C, Li C (2018) Glycyrrhizic acid induces human MDA-MB-231 breast cancer cell death and autophagy via the ROS-mitochondrial pathway. Oncol Rep 39:703–710

    CAS  Google Scholar 

  • Ming LJ, Yin AC (2013) Therapeutic effects of glycyrrhizic acid. Nat Prod Commun 8(3):415–418

    CAS  Google Scholar 

  • Morgan AM, Ibrahim MA, Hussien AM (2017) The potential protective role of Akropower against Atrazine- induced humoral immunotoxicity in rabbits. Biomed Pharmacother 96:610–615

    Article  CAS  Google Scholar 

  • Morgan A, Ibrahim MA, Galal MK, Ogaly HA, Abd-Elsalam RM (2018) Innovative perception on using tiron to modulate the hepatotoxicity induced by titanium dioxide nanoparticles in male rats. Biomed Pharmacother 103:553–561

    Article  CAS  Google Scholar 

  • Naito M (2008) Macrophage differentiation and function in health and disease. Pathol Int 58(3):143–155

    Article  CAS  Google Scholar 

  • OIE (2010) Terrestrial manual 2010 Chapter 2. 6. 2. Rabbit haemorrhagic disease

  • Pinhu L, Qin Y, Xiong B, You Y, Li J, Sooranna SR (2014) Overexpression of Fas and FasL is associated with infectious complications and severity of experimental severe acute pancreatitis by promoting apoptosis of lymphocytes. Inflammation 37(4):1202–1212

    Article  CAS  Google Scholar 

  • Raphael TJ, Kuttan G (2008) Effect of naturally occurring triterpenoids ursolic acid and Glycyrrhizic acid on the cell-mediated immune responses of metastatic tumor-bearing animals. Immunopharmacol Immunotoxicol 30:243–255

    Article  CAS  Google Scholar 

  • Rooney AA, Matulka RA, Luebke RW (2004) Developmental atrazine exposure suppresses immune function in male, but not female Sprague-Dawley rats. Toxicol Sci 76:366–375

    Article  Google Scholar 

  • Scialli AR, DeSesso JM, Breckenridge CB (2014) Developmental toxicity studies with Atrazine and its major metabolites in rats and rabbits. Birth Defects Res 101(Part B):199–214

    Article  CAS  Google Scholar 

  • Sil R, Ray D, Chakraborti AS (2015) Glycyrrhizin ameliorates metabolic syndrome-induced liver damage in experimental rat model. Mol Cell Biochem 409(1–2):177–189

    Article  CAS  Google Scholar 

  • Soltanian S (2016) Effect of atrazine on immunocompetence of red-eared slider turtle (Trachemys scripta). J Immunotoxicol 13(6):804–809

    Article  CAS  Google Scholar 

  • Song X, Li J, Wu Y, Zhang B, Li B (2015) Atrazine causes autophagy- and apoptosis-related neurodegenerative effects in dopaminergic neurons in the rat nigrostriatal dopaminergic system. Int J Mol Sci 13490–13506

    Article  CAS  Google Scholar 

  • Thueson LE, Emmons TR, Browning DL, Kreitinger JK, Shepherd DM, Wetzel SA (2015) In vitro exposure to the herbicide atrazine inhibits T cell activation, proliferation, and cytokine production and significantly increases the frequency of foxp31 regulatory T cells. Toxicol Sci 143(2):418–429

    Article  CAS  Google Scholar 

  • Yang PS, Kim DH, Lee YJ, Lee SE, Kang WJ, Chang HJ, Shin JS (2014) Glycyrrhizin, inhibitor of high mobility group box-1, attenuates monocrotaline-induced pulmonary hypertension and vascular remodeling in rats. Respir Res 15:148

    Article  CAS  Google Scholar 

  • Yang G, Zhang L, Ma L, Jiang R, Kuang G, Li K, Tie H, Wang B, Chen X, Xie T, Gong X, Wan J (2017) Glycyrrhetinic acid prevents acetaminophen induced acute liver injury via the inhibition of CYP2E1 expression and HMGB1 TLR4 signal activation in mice. Int Immunopharmacol 50:186–193

    Article  CAS  Google Scholar 

  • Yuan B, Liang S, Jin YX, Zhang MJ, Zhang JB, Kim NH (2017) Toxic effects of atrazine on porcine oocytes and possible mechanisms of action. PLoS ONE 12(6)

    Article  CAS  Google Scholar 

  • Zhang X, Wang M, Gao S, Ren R, Zheng J (2011) Atrazine-induced apoptosis of splenocytes in BALB/C mice. BMC Med 9:117

    Article  CAS  Google Scholar 

  • Zhao S, Liu J, Zhao F, Liu W, Li N, Suo Q, Zhao J, Zhao L (2013) Sub-acute exposure to the herbicide atrazine suppresses cell immune functions in adolescent mice. Bio Sci Trends 7(4):193–201

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Toxicology and Forensic Medicine Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt

    Ashraf M. Morgan & Ahmed M. Hussien

  2. Biochemistry and Chemistry of Nutrition Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt

    Marwa A. Ibrahim

Authors
  1. Ashraf M. Morgan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marwa A. Ibrahim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ahmed M. Hussien
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marwa A. Ibrahim.

Ethics declarations

The Local Research Ethical Committee of the Faculty of Veterinary Medicine, Cairo University, Egypt, approved the design of the experiment and the protocol follows the guidelines of the National Institutes of Health (NIH).

Additional information

Responsible Editor: Philippe Garrigues

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

Morgan, A.M., Ibrahim, M.A. & Hussien, A.M. Glycyrrhizic acid modulates the atrazine-induced apoptosis in rabbit spleen. Environ Sci Pollut Res 26, 34924–34930 (2019). https://doi.org/10.1007/s11356-019-06604-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-019-06604-x

Keywords

Search

Navigation