Skip to main content
SpringerLink
Log in

Acrylamide toxicity inhibits chick embryo hepatic alpha, mu, and pi-glutathione S-transferases: molecular dynamic simulations, substrate specificity, and docking

  • Original Article
  • Published:
Toxicology and Environmental Health Sciences Aims and scope Submit manuscript

Abstract

Purpose

This study aims to analyze the effect of acrylamide (AC) on hepatic cells of fertilized eggs. The subclasses of glutathione S-transferases and histological variations in serum and liver samples were analyzed in AC-induced chick embryos.

Results

Our results showed that the levels of alanine aminotransferase, serum aspartate aminotransferase, and alkaline phosphatase were significantly (p < 0.05) elevated in the liver of AC-treated chick embryo groups compared to control. In addition, AC-treated groups exhibited a significant (p < 0.05) decreased levels of glutathione content (GSH), glutathione reductase, GSTs, and increased malondialdehyde (MDA levels) in hepatic tissue of chick embryos. Furthermore, liver GSTs binding to various substrates such as CDNB, EPNP, pNPA, BSP, pNBC, ∆5-androstene-3, 17-dione, and EA was significantly (p < 0.05) decreased in AC-treated chick embryo groups compared to control. Histopathology examination (H&E staining) of the AC-treated chick embryo liver showed liver damage to a larger extent, specifically cytoplasmic vacuolation, pyknotic nuclei and blood vein congestion with patchy degeneration were observed. Further, the obtained in vitro results of α-GST, μ-GST, and π-GST were subjected to rigid receptor docking and quantum-polarized-ligand docking, which predicted that the in silico binding affinities of these classes of GSTs are in good correlation with strong hydrogen and van der Waal interactions to AC with −32.760, −26.254, −33.594 and −36.287, −33.980 and −36.363 kcal/mol MMGBSA (ΔGbind) scores respectively. The long-range molecular dynamics (50 ns) simulations have shown more consistency by AC.

Conclusion

The in vivo and in silico findings conclude that AC resulted in the dysfunction of the liver by altering its biochemical markers, α-GST, μ-GST, and π-GST, as well as by histological changes, and thus, AC is suggested as a more harmful agent in developing chick embryo.

Graphical abstract

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
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Availability of data and material

All data and materials are available upon request.

Abbreviations

AC:

Acrylamide

CYP2E1:

Cellular enzyme cytochrome P450 2E1

GST:

Glutathione-S-transferase

GSH:

Glutathione

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

ALP:

Alkaline phosphatase

RRD:

Rigid receptor docking

QPLD:

Quantum-polarized-ligand docking

GR:

Glutathione reductase

EPNP:

1,2-Epoxy-3-(p-nitro phenoxy)-propane

pNPA:

P-nitrophenyl acetate

BSP:

Bromosulfophthalein

pNBC:

P-nitrobenzol chloride

EA:

Ethacrynic acid

CHP:

Cumene hydroperoxide

MDS:

Molecular dynamic simulations

RMSD:

Root-mean-square deviation

PE:

Potential of the system

RMSF:

Root-mean-square fluctuations

rGyr:

Radius of gyration

References

  1. Shipp A, Lawrence G, Gentry R, McDonald T, Bartow H, Bounds J, Macdonald N, Clewell H, Allen B, VanLandingham C (2006) Acrylamide: review of toxicity data and dose-response analyses for cancer and noncancer effects. Crit Rev Toxicol 36(6–7):481–608. https://doi.org/10.1080/10408440600851377

    Article  CAS  PubMed  Google Scholar 

  2. El-Mehi AE, El-Sherif NM (2015) Influence of acrylamide on the gastric mucosa of adult albino rats and the possible protective role of rosemary. Tissue Cell 47(3):273–83.https://doi.org/10.1016/j.tice.2015.03.005.

  3. Elblehi SS, El Euony OI, El-Sayed YS (2020) Apoptosis and astrogliosis perturbations and expression of regulatory inflammatory factors and neurotransmitters in acrylamide-induced neurotoxicity under ω3 fatty acids protection in rats. Neurotoxicology 76:44–57. https://doi.org/10.1016/j.neuro.2019.10.004

    Article  CAS  PubMed  Google Scholar 

  4. Hamdy SM, El-Khayat Z, Farrag AR, Sayed ON, El-Sayed MM, Massoud D (2022) Hepatoprotective effect of Raspberry ketone and white tea against acrylamide-induced toxicity in rats. Drug ChemToxicol 45(2):722–730.https://doi.org/10.1080/01480545.2020.1772279.

  5. Zhang L, Zhang H, Miao Y, Wu S, Ye H, Yuan Y (2012) Protective effect of allicin against acrylamide-induced hepatocyte damage in vitro and in vivo. Food ChemToxicol 50(9):3306–12.https://doi.org/10.1016/j.fct.2012.05.060.

  6. Uthra C, Shrivastava S, Jaswal A, Sinha N, Reshi MS, Shukla S (2017) Therapeutic potential of quercetin against acrylamide induced toxicity in rats. Biomed Pharmacother 86:705–714.https://doi.org/10.1016/j.biopha.2016.12.065.

  7. Zamani E, Shokrzadeh M, Ziar A, Abedian-Kenari S, Shaki F (2018) Acrylamide attenuated immune tissues’ function via induction of apoptosis and oxidative stress: Protection by l-carnitine. Hum ExpToxicol 37(8):859–869. https://doi.org/10.1177/0960327117741753

    Article  CAS  Google Scholar 

  8. Acaroz U, Ince S, Arslan-Acaroz D, Gurler Z, Kucukkurt I, Demirel HH, Arslan HO, Varol N, Zhu K (2018) The ameliorative effects of boron against acrylamide-induced oxidative stress, inflammatory response, and metabolic changes in rats. Food ChemToxicol 118:745–752. https://doi.org/10.1016/j.fct.2018.06.029

    Article  CAS  Google Scholar 

  9. Sun J, Li M, Zou F, Bai S, Jiang X, Tian L, Ou S, Jiao R, Bai W (2018) Protection of cyanidin-3-O-glucoside against acrylamide- and glycidamide-induced reproductive toxicity in leydig cells. Food ChemToxicol 119:268–274. https://doi.org/10.1016/j.fct.2018.03.027

    Article  CAS  Google Scholar 

  10. Matoso V, Bargi-Souza P, Ivanski F, Romano MA, Romano RM (2019) Acrylamide: A review about its toxic effects in the light of developmental origin of health and disease (DOHaD) concept. Food Chem 283:422–430. https://doi.org/10.1016/j.foodchem.2019.01.054.

  11. Lee KS, Buck M, Houglum K, Chojkier M (1995) Activation of hepatic stellate cells by TGF alpha and collagen type I is mediated by oxidative stress through c-myb expression. J Clin Invest 96(5):2461–2468. https://doi.org/10.1172/JCI118304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Fennell TR, Sumner SC, Snyder RW, Burgess J, Friedman MA (2006) Kinetics of elimination of urinary metabolites of acrylamide in humans. ToxicolSci 93(2):256–267. https://doi.org/10.1093/toxsci/kfl069

    Article  CAS  Google Scholar 

  13. Jiang L, Cao J, An Y, Geng C, Qu S, Jiang L, Zhong L (2007) Genotoxicity of acrylamide in human hepatoma G2 (HepG2) cells. ToxicolIn Vitro 21(8):1486–92. https://doi.org/10.1016/j.tiv.2007.06.011.

  14. Dai Y, Rashba-Step J, Cederbaum AI (1993) Stable expression of human cytochrome P4502E1 in HepG2 cells: characterization of catalytic activities and production of reactive oxygen intermediates. Biochemistry 32(27):6928–6937. https://doi.org/10.1021/bi00078a017

    Article  CAS  PubMed  Google Scholar 

  15. Doroshyenko O, Fuhr U, Kunz D, Frank D, Kinzig M, Jetter A, Reith Y, Lazar A, Taubert D, Kirchheiner J, Baum M, Eisenbrand G, Berger FI, Bertow D, Berkessel A, SörgelF SE, Tomalik-Scharte D (2009) In vivo role of cytochrome P450 2E1 and glutathione-S-transferase activity for acrylamide toxicokinetics in humans. Cancer Epidemiol Biomarkers Prev 18(2):433–443. https://doi.org/10.1158/1055-9965.EPI-08-0832

    Article  CAS  PubMed  Google Scholar 

  16. Hayes JD, Pulford DJ (1995) The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev BiochemMolBiol 30(6):445–600. https://doi.org/10.3109/10409239509083491

    Article  CAS  Google Scholar 

  17. Shi C, Wang X, Xiao Z, Wang R, Qiao Y, Kan G (2020) Cloning, characterization and expression analysis of glutathione S-transferase from the Antarctic yeast Rhodotorulamucilaginosa AN5. Protein ExprPurif 167:105518. https://doi.org/10.1016/j.pep.2019.105518.

  18. Lee BY, Choi BS, Kim MS, Park JC, Jeong CB, Han J, Lee JS (2019) The genome of the freshwater water flea Daphnia magna: a potential use for freshwater molecular ecotoxicology. AquatToxicol 210:69–84. https://doi.org/10.1016/j.aquatox.2019.02.009

    Article  CAS  Google Scholar 

  19. Flanagan JU, Smythe ML (2011) Sigma-class glutathione transferases. Drug Metab Rev 43(2):194–214. https://doi.org/10.3109/03602532.2011.560157

    Article  CAS  PubMed  Google Scholar 

  20. Howie AF, Forrester LM, Glancey MJ, Schlager JJ, Powis G, Beckett GJ, Hayes JD, Wolf CR (1990) Glutathione S-transferase and glutathione peroxidase expression in normal and tumour human tissues. Carcinogenesis 11(3):451–458. https://doi.org/10.1093/carcin/11.3.451

    Article  CAS  PubMed  Google Scholar 

  21. Thyagaraju K, Hemavathi B, Vasundhara K, Rao AD, Devi KN (2005) Comparative study on glutathione transferases of rat brain and testis under the stress of phenobarbitol and beta-methylcholanthrene. J Zhejiang UnivSci B 6(8):759–769. https://doi.org/10.1631/jzus.2005.B0759

    Article  CAS  Google Scholar 

  22. Listowsky I, Rowe JD, Patskovsky YV, Tchaikovskaya T, Shintani N, Novikova E, Nieves E (1998) Human testicular glutathione S-transferases: insights into tissue-specific expression of the diverse subunit classes. ChemBiol Interact 24(111–112):103–112. https://doi.org/10.1016/s0009-2797(97)00154-3

    Article  Google Scholar 

  23. Shang W, Liu WH, Zhao XH, Sun QJ, Bi JZ, Chi ZF (2008) Expressions of glutathione S-transferase alpha, mu, and pi in brains of medically intractable epileptic patients. BMC Neurosci 18(9):67. https://doi.org/10.1186/1471-2202-9-67

    Article  CAS  Google Scholar 

  24. Hayes JD, Mantle TJ (1986) Inhibition of hepatic and extrahepatic glutathione S-transferases by primary and secondary bile acids. Biochem J 15;233(2):407–15. https://doi.org/10.1042/bj2330407

  25. Dasari S, Ganjayi MS, Yellanurkonda P, Basha S, Meriga B (2018) Role of glutathione S-transferases in detoxification of a polycyclic aromatic hydrocarbon, methylcholanthrene. ChemBiol Interact 294:81–90. https://doi.org/10.1016/j.cbi.2018.08.023

    Article  CAS  Google Scholar 

  26. Barbosa VB, Costa-Silva PF, Araújo-Silva H, Miranda G, Correia-Pinto J, Moura RS (2022) Molecular insights of Hippo signaling in the chick developing lung. Biochim Biophys Acta Gene Regul Mech 1866(1):194904. https://doi.org/10.1016/j.bbagrm.2022.194904

  27. Song R, Shurson GC (2013) Evaluation of lipid peroxidation level in corn dried distillers grains with solubles. J Anim Sci 91(9):4383–4388. https://doi.org/10.2527/jas.2013-6319

    Article  CAS  PubMed  Google Scholar 

  28. Tekin S, Seven E (2022) Assessment of serum catalase, reduced glutathione, and superoxide dismutase activities and malondialdehyde levels in keratoconus patients. Eye (Lond) 36(10):2062–2066. https://doi.org/10.1038/s41433-021-01753-1

    Article  CAS  PubMed  Google Scholar 

  29. Mannervik B, Danielson UH (1988) Glutathione transferases–structure and catalytic activity. CRC Crit Rev Biochem 23(3):283–337. https://doi.org/10.3109/10409238809088226

    Article  CAS  PubMed  Google Scholar 

  30. Pasala C, Katari SK, Nalamolu RM, Bitla AR, Amineni U (2019) In silico probing exercises, bioactive-conformational and dynamic simulations strategies for designing and promoting selective therapeutics against Helicobacter pylori strains. J Mol Graph Model 92:167–179. https://doi.org/10.1016/j.jmgm.2019.07.015

    Article  CAS  PubMed  Google Scholar 

  31. Pasala C, Chilamakuri CSR, Katari SK, Nalamolu RM, Bitla AR, Amineni U (2019b) Epitope-driven common subunit vaccine design against H. pylori strains. J Biomol Struct Dyn 37(14):3740–3750. https://doi.org/10.1080/07391102.2018.1526714.

  32. Pasala C, Katari SK, Nalamolu RM, Bitla AR, Amineni U (2019) Hierarchical-clustering, scaffold-mining exercises and dynamics simulations for effectual inhibitors against lipid-a biosynthesis of Helicobacter pylori. Cell MolBioeng 12(3):255–274. https://doi.org/10.1007/s12195-019-00572-5

    Article  Google Scholar 

  33. Friesner RA, Murphy RB, Repasky MP, Frye LL, Greenwood JR, Halgren TA, Sanschagrin PC, Mainz DT (2006) Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J Med Chem 49(21):6177–6196. https://doi.org/10.1021/jm051256o

    Article  CAS  PubMed  Google Scholar 

  34. Nagalakshmamma V, Venkataswamy M, Pasala C, Umamaheswari A, Thyagaraju K, Nagaraju C, Chalapathi PV (2020) Design, synthesis, anti-tobacco mosaic viral and molecule docking simulations of urea/thiourea derivatives of 2-(piperazine-1-yl)-pyrimidine and 1-(4-Fluoro/4-Chloro phenyl)-piperazine and 1-(4-Chloro phenyl)-piperazine—a study. Bioorg Chem 102:104084. https://doi.org/10.1016/j.bioorg.2020.104084.

  35. Elfimova N, Schlattjan M, Sowa JP, Dienes HP, Canbay A, Odenthal M (2012) Circulating microRNAs: promising candidates serving as novel biomarkers of acute hepatitis. Front Physiol 3:476. https://doi.org/10.3389/fphys.2012.00476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Honig LS, Rosenberg RN (2000) Apoptosis and neurologic disease. Am J Med 108(4):317–330. https://doi.org/10.1016/s0002-9343(00)00291-6

    Article  CAS  PubMed  Google Scholar 

  37. Lopachin RM, Decaprio AP (2005) Protein adduct formation as a molecular mechanism in neurotoxicity. ToxicolSci 86(2):214–225. https://doi.org/10.1093/toxsci/kfi197

    Article  CAS  Google Scholar 

  38. Ahmadabad MA, Naeimi A, Keymoradzadeh A, Faghani S, Ahmadabad MA, Boroujeni NA, Mohammadpour H, Saberi A. Evaluation of De Ritis (AST/ALT), ALP/ALT, and AST/ALP ratios as prognostic factors in patients with acute ischemic stroke. BMC Neurol 22(1):450. https://doi.org/10.1186/s12883-022-02989-4

  39. Dasari S, Gonuguntla S, Yellanurkonda P, Nagarajan P, Meriga B (2019) Sensitivity of glutathione S-transferases to high doses of acrylamide in albino wistar rats: affinity purification, biochemical characterization and expression analysis. Ecotoxicol Environ Saf 182:109416. https://doi.org/10.1016/j.ecoenv.2019.109416.

Download references

Acknowledgements

The authors are thankful to DST-FIST and DST-PURSE, S. V. University, Tirupati for providing facilities.The authors are grateful to the University Grants Commission (UGC), Government of India, New Delhi, for providing a fellowship to carry out the research (File No. F/PDFSS-2015-17-AND-10953)

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Also, no sponsorships in any way have been existed.

Author information

Authors and Affiliations

  1. Department of Biochemistry, Sri Venkateswara University, Tirupati, Andhra Pradesh, 517502, India

    Venkataswamy Mallepogu, Balaji Meriga & Thyaga Raju Kedam

  2. Department of Chemistry, Rayalaseema University, Kurnool, Andhra Pradesh, India

    Rani E. Mallapu & Nagalakshmamma Vadabingi

  3. Bioinformatics Centre, Department of Bioinformatics, SVIMS University, Tirupati, Andhra Pradesh, India

    Chiranjeevi Pasala & Umamaheswari Amineni

  4. Biomaterials and Bioengineering Research Laboratory, Department of Biotechnology, Mizoram University, Pachhunga University College Campus, Mizoram, India

    Jayasekhar Babu Punuri

Authors
  1. Venkataswamy Mallepogu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rani E. Mallapu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nagalakshmamma Vadabingi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chiranjeevi Pasala
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jayasekhar Babu Punuri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Umamaheswari Amineni
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Balaji Meriga
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Thyaga Raju Kedam
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

VM contributed to methodology, investigation, data curation, writing-original draft, visualization. JBP and BM contributed to investigation, methodology, data curation. NV and REM contributed to investigation, formal analysis. CP and UMA contributed to formal analysis, investigation, methodology. TK contributed to conceptualization; methodology; supervision; review and editing.

Corresponding author

Correspondence to Thyaga Raju Kedam.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mallepogu, V., Mallapu, R.E., Vadabingi, N. et al. Acrylamide toxicity inhibits chick embryo hepatic alpha, mu, and pi-glutathione S-transferases: molecular dynamic simulations, substrate specificity, and docking. Toxicol. Environ. Health Sci. 15, 289–302 (2023). https://doi.org/10.1007/s13530-023-00183-8

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13530-023-00183-8

Keywords

Search

Navigation