Home >Current Issue

Volume: 6, Issue: 6, Nov-Dec, 2018
DOI: 10.7324/JABB.2018.60613

Research Article

Assessment of biomarkers in acrylamide-induced neurotoxicity and brain histopathology in rat

Sreenivasulu Dasari1, Muni Swamy Ganjayi1, Sailaja Gonuguntla1, Keerthi Ramineedu1, Prabhakar Yellanur Konda2, Balaji Meriga1

  Author Affiliations


Abstract

The effects of acrylamide (ACR), a synthetic neurotoxic chemical compound on non-enzymatic and enzymatic stress markers and brain histopathology, were studied in Wistar rats. ACR (50 mg/300 ml) was ingested through drinking water on alternative days, and brain tissues were collected on the 13th and 27th days post-ingestion for analysis. Results revealed that ACR causes significant increase in non-enzymatic stress markers such as lipid peroxidation (P < 0.05) and nitric oxide (P < 0.05), but depletion of glutathione (P < 0.05). Enzymatic stress markers, glutathione peroxidase, and glutathione s-transferase activities significantly increased (P < 0.05) at the 13th day post-ingestion, but decreased at the 27th day. However, acetylcholine esterase activity dropped significantly (P < 0.05) at the 13th and 27th days post-ingestion. In addition, ACR induced histological changes in brain such as degeneration of pyramidal and glial cells, mild vacuolation of pyramidal cells, and spongiosis in glia cells on 13th day post-ingestion. On the 27th day, brain tissue necrosis and pyknosis, necrosis of neurons and neurophagia, focal gliosis, and demyelination of nerve fibers were observed. In conclusion, ACR influences non-enzymatic and enzymatic stress markers in brain tissue and induces neurodegeneration in Wistar rats.

Keywords:

Acrylamide, Brain degeneration, Stress markers.



Citation: Dasari S, Ganjayi MS, Gonuguntla S, Ramineedu K, Konda PY, Meriga B. Assessment of biomarkers in acrylamide-induced neurotoxicity and brain histopathology in rat. J App Biol Biotech. 2018;6(06):79-86. DOI: 10.7324/JABB.2018.60613


Copyright: Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

References

1. Meng FG, Zhou HW, Zhou HM. Effects of acrylamide on creatine kinase from rabbit muscle. Int J Biochem Cell Biol 2001;33:1064-70. https://doi.org/10.1016/S1357-2725(01)00079-6

2. Boettcher MI, Schettgen T, K\ütting B, Pischetsrieder M, Angerer J. Mercapturic acids of acrylamide and glycidamide as biomarkers of the internal exposure to acrylamide in the general population. Mutat Res 2005;580:167-76. https://doi.org/10.1016/j.mrgentox.2004.11.010

3. Tareke E, Rydberg P, Karlsson P, Eriksson S, Törnqvist M. Analysis of acrylamide, a carcinogen formed in heated foodstuffs. J Agric Food Chem 2002;50:4998-5006. https://doi.org/10.1021/jf020302f

4. Mottram DS, Wedzicha BL, Dodson AT. Acrylamide is formed in the maillard reaction. Nature 2002;419:448-9. https://doi.org/10.1038/419448a

5. Prasad SN. Evidence of acrylamide induced oxidative stress and neurotoxicity in Drosophila melanogaster-Its amelioration with spice active enrichment: Relevance to neuropathy. Neurotoxicology 2012;33:1254-64. https://doi.org/10.1016/j.neuro.2012.07.006

6. Rahman T, Hosen I, Islam MT, Shekhar HU. Oxidative stress and human health. Adv Biosci Biotechnol 2012;3:997. https://doi.org/10.4236/abb.2012.327123

7. Greń A. Effects of vitamin E, C and D supplementation on inflammation and oxidative stress in streptozotocin-induced diabetic mice. Int J Vitam Nutr Res 2013;83:168-75. https://doi.org/10.1024/0300-9831/a000156

8. Katz R. Biomarkers and surrogate markers: An FDA perspective. NeuroRx 2004;1:189-95. https://doi.org/10.1602/neurorx.1.2.189

9. Niki E, Yoshida Y, Saito Y, Noguchi N. Lipid peroxidation: Mechanisms, inhibition, and biological effects. Biochem Biophys Res Commun 2005;338:668-76. https://doi.org/10.1016/j.bbrc.2005.08.072

10. Dotan Y, Lichtenberg D, Pinchuk I. Lipid peroxidation cannot be used as a universal criterion of oxidative stress. Prog Lipid Res 2004;43:200-27. https://doi.org/10.1016/j.plipres.2003.10.001

11. Gutteridge JM. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem 1995;41:1819-28.

12. Maiorino FM, Brigelius-Floh\é R, Aumann KD, Roveri A, Schomburg D, Floh\é L. Diversity of glutathione peroxidases. Methods Enzymol 1995;252:38-53. https://doi.org/10.1016/0076-6879(95)52007-4

13. Takebe G, Yarimizu J, Saito Y, Hayashi T, Nakamura H, Yodoi J, et al. A comparative study on the hydroperoxide and thiol specificity of the glutathione peroxidase family and selenoprotein P. J Biol Chem 2002;277:41254-8. https://doi.org/10.1074/jbc.M202773200

14. Irmak MK, Fadillioglu E, Sogut S, Erdogan H, Gulec M, Ozer M. Effects of caffeic acid phenethyl ester and alpha-tocopherol on reperfusion injury in rat brain. Cell Biochem Funct 2003;21:283-9. https://doi.org/10.1002/cbf.1024

15. Moncada S, Higgs EA. Molecular mechanisms and therapeutic strategies related to nitric oxide. FASEB J 1995;9:1319-30. https://doi.org/10.1096/fasebj.9.13.7557022

16. Singh S, Gupta AK. Nitric oxide: Role in tumour biology and iNOS/ NO-based anticancer therapies. Cancer Chemother Pharmacol 2011;67:1211-24. https://doi.org/10.1007/s00280-011-1654-4

17. Garthwaite J. Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci 1991;14:60-7. https://doi.org/10.1016/0166-2236(91)90022-M

18. Wildemann B, Bicker G. Nitric oxide and cyclic GMP induce vesicle release at drosophila neuromuscular junction. J Neurobiol 1999;39:337-46. https://doi.org/10.1002/(SICI)1097-4695(19990605)39:3< 337::AID-NEU1>3.0.CO;2-9

19. Meffert MK, Calakos NC, Scheller RH, Schulman H. Nitric oxide modulates synaptic vesicle docking fusion reactions. Neuron 1996;16:1229-36. https://doi.org/10.1016/S0896-6273(00)80149-X

20. Boehning D, Snyder SH. Novel neural modulators. Annu Rev Neurosci 2003;26:105-31. https://doi.org/10.1146/annurev.neuro.26.041002.131047

21. Seyidova D, Aliyev A, Rzayev N, Obrenovich M, Lamb BT, Smith MA, et al. The role of nitric oxide in the pathogenesis of brain lesions during the development of Alzheimer's disease. In Vivo 2004;18:325-33.

22. Zhu YJ, Zeng T, Zhu YB, Yu SF, Wang QS, Zhang LP, et al. Effects of acrylamide on the nervous tissue antioxidant system and sciatic nerve electrophysiology in the rat. Neurochem Res 2008;33:2310-7. https://doi.org/10.1007/s11064-008-9730-9

23. Kopanska M, Lukac N, Kapusta E, Formicki G. Acrylamide influence on activity of acetylcholinesterase, thiol groups, and malondialdehyde content in the brain of swiss mice. J Biochem Mol Toxicol 2015;29:472-8. https://doi.org/10.1002/jbt.21717

24. Paulsson B, Rannug A, Henderson AP, Golding BT, Törnqvist M, Warholm M, et al. In vitro studies of the influence of glutathione transferases and epoxide hydrolase on the detoxification of acrylamide and glycidamide in blood. Mutat Res 2005;580:53-9. https://doi.org/10.1016/j.mrgentox.2004.11.006

25. Yousef MI, El-Demerdash FM. Acrylamide-induced oxidative stress and biochemical perturbations in rats. Toxicology 2006;219:133-41. https://doi.org/10.1016/j.tox.2005.11.008

26. Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: Impact on human health. Pharm Rev 2010;4:118-26. https://doi.org/10.4103/0973-7847.70902

27. Gawryluk JW, Wang JF, Andreazza AC, Shao L, Young LT. Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders. Int J Neuropsychopharmacol 2011;14:123-30. https://doi.org/10.1017/S1461145710000805

28. Schuliga M, Chouchane S, Snow ET. Upregulation of glutathione-related genes and enzyme activities in cultured human cells by sublethal concentrations of inorganic arsenic. Toxicol Sci 2002;70:183-92. https://doi.org/10.1093/toxsci/70.2.183

29. Mills GC. Hemoglobin catabolism. I. Glutathione peroxidase, an erythrocyte enzyme which protects hemoglobin from oxidative breakdown. J Biol Chem 1957;229:189-97.

30. Bela K, Horváth E, Gall\é Á, Szabados L, Tari I, Csiszár J. Plant glutathione peroxidases: Emerging role of the antioxidant enzymes in plant development and stress responses. J Plant Physiol 2015;176:192-201. https://doi.org/10.1016/j.jplph.2014.12.014

31. Brigelius-Floh\é R, Banning A, Schnurr K. Selenium-dependent enzymes in endothelial cell function. Antioxid Redox Signal 2003;5:205-15. https://doi.org/10.1089/152308603764816569

32. Margis R, Dunand C, Teixeira FK, Margis-Pinheiro M. Glutathione peroxidase family–an evolutionary overview. FEBS J 2008;275:3959-70. https://doi.org/10.1111/j.1742-4658.2008.06542.x

33. Power JH, Blumbergs PC. Cellular glutathione peroxidase in human brain: Cellular distribution, and its potential role in the degradation of lewy bodies in Parkinson's disease and dementia with lewy bodies. Acta Neuropathol 2009;117:63-73. https://doi.org/10.1007/s00401-008-0438-3

34. Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 2006;443:787-95. https://doi.org/10.1038/nature05292

35. Dasuri K, Zhang L, Keller JN. Oxidative stress, neurodegeneration, and the balance of protein degradation and protein synthesis. Free Radic Biol Med 2013;62:170-85. https://doi.org/10.1016/j.freeradbiomed.2012.09.016

36. Ursini F, Mariorino M, Brigelius-Flohe R, Aumann KD, Roveri A, Schomburg D, et al. Diversity of glutathione peroxidase. Methods Enzymol 1995;252:38-53. https://doi.org/10.1016/0076-6879(95)52007-4

37. Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu Rev Pharmacol Toxicol 2005;45:51-88. https://doi.org/10.1146/annurev.pharmtox.45.120403.095857

38. Strange RC, Jones PW, Fryer AA. Glutathione S-transferase: Genetics and role in toxicology. Toxicol Lett 2000;112-113:357-63. https://doi.org/10.1016/S0378-4274(99)00230-1

39. Senhaji N, Kassogue Y, Fahimi M, Serbati N, Badre W, Nadifi S, et al. Genetic polymorphisms of multidrug resistance gene-1 (MDR1/ABCB1) and glutathione S-transferase gene and the risk of inflammatory bowel disease among moroccan patients. Mediators Inflamm 2015;2015:248060. https://doi.org/10.1155/2015/248060

40. Nebert DW, Vasiliou V. Analysis of the glutathione S-transferase (GST) gene family. Hum Genomics 2004;1:460-4. https://doi.org/10.1186/1479-7364-1-6-460

41. Hayes JD, Strange RC. Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology 2000;61:154-66. https://doi.org/10.1159/000028396

42. Mansvelder HD, De Rover M, McGehee DS, Brussaard AB. Cholinergic modulation of dopaminergic reward areas: Upstream and downstream targets of nicotine addiction. Eur J Pharmacol 2003;480:117-23. https://doi.org/10.1016/j.ejphar.2003.08.099

43. Massouli\é J, Pezzementi L, Bon S, Krejci E, Vallette FM. Molecular and cellular biology of cholinesterases. Prog Neurobiol 1993;41:31-91. https://doi.org/10.1016/0301-0082(93)90040-Y

44. Li B, Stribley JA, Ticu A, Xie W, Schopfer LM, Hammond P, et al. Abundant tissue butyrylcholinesterase and its possible function in the acetylcholinesterase knockout mouse. J Neurochem 2000;75:1320-31. https://doi.org/10.1046/j.1471-4159.2000.751320.x

45. Melo JB, Agostinho P, Oliveira CR. Involvement of oxidative stress in the enhancement of acetylcholinesterase activity induced by amyloid beta-peptide. Neurosci Res 2003;45:117-27. https://doi.org/10.1016/S0168-0102(02)00201-8

46. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951;193:265-75.

47. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8. https://doi.org/10.1016/0003-2697(79)90738-3

48. Jabłońska E, Kiersnowska-Rogowska B, Ratajczak W, Rogowski F, Sawicka-Powierza J. Reactive oxygen and nitrogen species in the course of B-CLL. Adv Med Sci 2007;52:154-8.

49. Kurtel H, Granger DN, Tso P, Grisham MB. Vulnerability of intestinal interstitial fluid to oxidant stress. Am J Physiol 1992;263:G573-8.

50. Wendel A. Glutathione peroxidase. Methods Enzymol 1981;77:325-33. https://doi.org/10.1016/S0076-6879(81)77046-0

51. Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 1974;249:7130-9.

52. Ellman GL, Courtney KD, Andres V Jr. Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961;7:88-95. https://doi.org/10.1016/0006-2952(61)90145-9

53. Humason GL. Specific Staining Methods. Animal Tissue Techniques. San Francisco, CA: WH Freeman and Co; 1972.

54. Cadenas E, Davies KJ. Mitochondrial free radical generation, oxidative stress, and aging1. Free Radic Biol Med 2000;29:222-30. https://doi.org/10.1016/S0891-5849(00)00317-8

55. Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol 2014;24:R453-62. https://doi.org/10.1016/j.cub.2014.03.034

56. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J, et al. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007;39:44-84. https://doi.org/10.1016/j.biocel.2006.07.001

57. Vasseur P, Leguille C. Defense systems of benthic invertebrates in response to environmental stressors. Environ Toxicol 2004;19:433-6. https://doi.org/10.1002/tox.20024

58. Maiese K, Chong ZZ, Hou J, Shang YC. Oxidative stress: Biomarkers and novel therapeutic pathways. Exp Gerontol 2010;45:217-34. https://doi.org/10.1016/j.exger.2010.01.004

59. Dix TA, Aikens J. Mechanisms and biological relevance of lipid peroxidation initiation. Chem Res Toxicol 1993;6:2-18. https://doi.org/10.1021/tx00031a001

60. Lucca G, Comim CM, Valvassori SS, R\éus GZ, Vuolo F, Petronilho F, et al. Effects of chronic mild stress on the oxidative parameters in the rat brain. Neurochem Int 2009;54:358-62. https://doi.org/10.1016/j.neuint.2009.01.001

61. Ferrario R, Takahashi K, Fogo A, Badr KF, Munger KA. Consequences of acute nitric oxide synthesis inhibition in experimental glomerulonephritis. J Am Soc Nephrol 1994;4:1847-54.

62. Nussler AK, Billiar TR. Inflammation, immunoregulation, and inducible nitric oxide synthase. J Leukoc Biol 1993;54:171-8. https://doi.org/10.1002/jlb.54.2.171

63. Kim K. Effect of subchronic acrylamide exposure on the expression of neuronal and inducible nitric oxide synthase in rat brain. J Biochem Mol Toxicol 2005;19:162-8. https://doi.org/10.1002/jbt.20069

64. Eren I, Naziroğlu M, Demirdaş A, Celik O, Uğuz AC, Altunbaşak A, et al. Venlafaxine modulates depression-induced oxidative stress in brain and medulla of rat. Neurochem Res 2007;32:497-505. https://doi.org/10.1007/s11064-006-9258-9

65. Dringen R, Hirrlinger J. Glutathione pathways in the brain. Biol Chem 2003;384:505-16. https://doi.org/10.1515/BC.2003.059

66. Dringen R. Metabolism and functions of glutathione in brain. Prog Neurobiol 2000;62:649-71. https://doi.org/10.1016/S0301-0082(99)00060-X

67. Gandhi S, Abramov AY. Mechanism of oxidative stress in neurodegeneration. Oxid Med Cell Longev 2012;2012:428010. https://doi.org/10.1155/2012/428010

68. Pe-a-Llopis S, Ferrando MD, Pe-a JB. Impaired glutathione redox status is associated with decreased survival in two organophosphate-poisoned marine bivalves. Chemosphere 2002;47:485-97. https://doi.org/10.1016/S0045-6535(01)00323-X

69. Trevisan R, Arl M, Sacchet CL, Engel CS, Danielli NM, Mello DF, et al. Antioxidant deficit in gills of pacific oyster (Crassostrea gigas) exposed to chlorodinitrobenzene increases menadione toxicity. Aquat Toxicol 2012;108:85-93. https://doi.org/10.1016/j.aquatox.2011.09.023

70. Brigelius-Floh\é R, Maiorino M. Glutathione peroxidases. Biochim Biophys Acta 2013;1830:3289-303. https://doi.org/10.1016/j.bbagen.2012.11.020

71. Chatziargyriou V, Dailianis S. The role of selenium-dependent glutathione peroxidase (Se-GPx) against oxidative and genotoxic effects of mercury in haemocytes of mussel Mytilus galloprovincialis (Lmk.). Toxicol In Vitro 2010;24:1363-72. https://doi.org/10.1016/j.tiv.2010.04.008

72. Dasari S, Gonuguntla S, Meriga B, Kedam T. Adverse influence of \ß-methylcholanthrene on detoxification function of chick embryo brain glutathione S-transferases and degenerative changes of brain. J Appl Pharm Sci 2018;8:111-9.

73. Trevisan R, Mello DF, Uliano-Silva M, Delapedra G, Arl M, Dafre AL, et al. The biological importance of glutathione peroxidase and peroxiredoxin backup systems in bivalves during peroxide exposure. Mar Environ Res 2014;101:81-90. https://doi.org/10.1016/j.marenvres.2014.09.004

74. Coleman J, Blake-Kalff M, Davies E. Detoxification of xenobiotics by plants: chemical modification and vacuolar compartmentation. Trends Plant Sci 1997;2:144-51. https://doi.org/10.1016/S1360-1385(97)01019-4

75. Laborde E. Glutathione transferases as mediators of signaling pathways involved in cell proliferation and cell death. Cell Death Differ 2010;17:1373-80. https://doi.org/10.1038/cdd.2010.80

76. Board PG, Coggan M, Chelvanayagam G, Easteal S, Jermiin LS, Schulte GK, et al. Identification, characterization, and crystal structure of the omega class glutathione transferases. J Biol Chem 2000;275:24798-806. https://doi.org/10.1074/jbc.M001706200

77. Dasari S, Ganjayi MS, Oruganti L, Balaji H, Meriga B. Glutathione s-transferases detoxify endogenous and exogenous toxic agents-minireview. J Dairy Vet Anim Res 2017;5:154. https://doi.org/10.15406/jdvar.2017.05.00154

78. Di Pietro G, Magno LA, Rios-Santos F. Glutathione S-transferases: An overview in cancer research. Expert Opin Drug Metab Toxicol 2010;6:153-70. https://doi.org/10.1517/17425250903427980

79. Mehri S, Abnous K, Khooei A, Mousavi SH, Shariaty VM, Hosseinzadeh H, et al. Crocin reduced acrylamide-induced neurotoxicity in wistar rat through inhibition of oxidative stress. Iran J Basic Med Sci 2015;18:902-8.

80. Hart AD. Relationships between behavior and the inhibition of acetylcholinesterase in birds exposed to organophosphorus pesticides. Environ Toxicol Chem 1993;12:321-36. https://doi.org/10.1002/etc.5620120215

81. Friboulet A, Rieger F, Goudou D, Amitai G, Taylor P. Interaction of an organophosphate with a peripheral site on acetylcholinesterase. Biochemistry 1990;29:914-20. https://doi.org/10.1021/bi00456a010

82. Singh AK, Saxena PN, Sharma HN. Stress induced by beta-cyfluthrin, a type-2 pyrethroid, on brain biochemistry of Albino rat (Rattus norvegicus). Biol Med 2009;1:74-86.

83. T\üzmen MN, Candan N, Kaya E. The evaluation of altered antioxidative defense mechanism and acetylcholinesterase activity in rat brain exposed to chlorpyrifos, deltamethrin, and their combination. Toxicol Mech Methods 2007;17:535-40. https://doi.org/10.1080/15376510701380463

84. Sharma P, Firdous S, Singh R. Neurotoxic effect of cypermethrin and protective role of resveratrol in Wistar rats. Int J Nutr Pharmacol Neurol Dis 2014;4:104. https://doi.org/10.4103/2231-0738.129598

85. Anderson CM, Swanson RA. Astrocyte glutamate transport: Review of properties, regulation, and physiological functions. Glia 2000;32:1-4. https://doi.org/10.1002/1098-1136(200010)32:1< 1::AID-GLIA10>3.0.CO;2-W

86. Cerbai F, Lana D, Nosi D, Petkova-Kirova P, Zecchi S, Brothers HM, et al. The neuron-astrocyte-microglia triad in normal brain ageing and in a model of neuroinflammation in the rat hippocampus. PLoS One 2012;7:e45250. https://doi.org/10.1371/journal.pone.0045250

87. Li Y, Tan MS, Jiang T, Tan L. Microglia in Alzheimer's disease. Biomed Res Int 2014;2014:1-7. https://doi.org/10.1155/2014/437483

88. Jangir BL, Mahaprabhu R, Rahangadale S, Bhandarkar AG, Kurkure NV. Neurobehavioral alterations and histopathological changes in brain and spinal cord of rats intoxicated with acrylamide. Toxicol Ind Health 2016;32:526-40. https://doi.org/10.1177/0748233713505893

89. Zhao M, Wang P, Zhu Y, Liu X, Hu X, Chen F, et al. The chemoprotection of a blueberry anthocyanin extract against the acrylamide-induced oxidative stress in mitochondria: Unequivocal evidence in mice liver. Food Funct 2015;6:3006-12. https://doi.org/10.1039/C5FO00408J

Article Metrics

Similar Articles

Asparagus racemosus extract increases the life span in Drosophila melanogaster
K. V. Kiran Kumar, K. S. Prasanna, J. S. Ashadevi