Role of Oxidative Stress, MAPKinase and Apoptosis Pathways in the Protective Effects of Thymoquinone Against Acrylamide-Induced Central Nervous System Toxicity in Rat

Overview

Journal Neurochem Res

Specialties Chemistry
Neurology

Date 2019 Nov 16

PMID 31728856

Citations 20

Authors

Jamshid Tabeshpour

Soghra Mehri

Khalil Abnous

Hossein Hosseinzadeh

Affiliations

Soon will be listed here.

Abstract

The present study evaluated biochemical endpoints characterizing acrylamide (ACR) neurotoxicity in the cortex of rats, following the possible neuroprotective activity of thymoquinone (TQ), an active constituent of Nigella sativa. ACR (50 mg/kg, intraperitoneal [i.p.]) concurrently with TQ (2.5, 5 and 10 mg/kg, i.p.) for 11 days were administered to rats. As positive control, vitamin E was used. After 11 days of injections, narrow beam test (NBT) was performed. The levels of reduced glutathione (GSH) and malondialdehyde (MDA) were measured and Western blotting was done for mitogen-activated protein kinases (MAPKinases) and apoptosis pathways proteins in the rats' cortex. Additionally, Evans blue assay was done to evaluate the integrity of blood brain barrier (BBB). Administration of ACR significantly induced gait abnormalities. A significant decrease and increase in the levels of GSH and MDA was observed in the cortex of ACR-treated rats, respectively. The elevation in the levels of caspases 3 and 9, glial fibrillary acidic protein (GFAP) content, and Bax/Bcl-2, P-P38/P38 and P-JNK/JNK ratios accompanied by reduction in myelin basic protein (MBP) content and P-ERK/ERK ratio were noticed in the ACR group. TQ (5 mg/kg) improved gait abnormalities, and restored these changes. ACR affected the integrity of BBB while TQ was able to maintain the integrity of this barrier. TQ reversed the alterations in the protein contents of MAP kinase and apoptosis signaling pathways as well as MBP and GFAP contents, induced by ACR. It protected against ACR-mediated neurotoxicity, partly through its antioxidant and antiapoptotic properties.

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References

Gokce E, Kahveci R, Gokce A, Cemil B, Aksoy N, Sargon M . Neuroprotective effects of thymoquinone against spinal cord ischemia-reperfusion injury by attenuation of inflammation, oxidative stress, and apoptosis. J Neurosurg Spine. 2016; 24(6):949-59. DOI: 10.3171/2015.10.SPINE15612. View

Ullah I, Ullah N, Naseer M, Lee H, Kim M . Neuroprotection with metformin and thymoquinone against ethanol-induced apoptotic neurodegeneration in prenatal rat cortical neurons. BMC Neurosci. 2012; 13:11. PMC: 3317821. DOI: 10.1186/1471-2202-13-11. View

Prasad S, Muralidhara . Mitigation of acrylamide-induced behavioral deficits, oxidative impairments and neurotoxicity by oral supplements of geraniol (a monoterpene) in a rat model. Chem Biol Interact. 2014; 223:27-37. DOI: 10.1016/j.cbi.2014.08.016. View

Parng C, Roy N, Ton C, Lin Y, McGrath P . Neurotoxicity assessment using zebrafish. J Pharmacol Toxicol Methods. 2006; 55(1):103-12. DOI: 10.1016/j.vascn.2006.04.004. View

Hol E, Pekny M . Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system. Curr Opin Cell Biol. 2015; 32:121-30. DOI: 10.1016/j.ceb.2015.02.004. View

Xia Z, Dickens M, Raingeaud J, Davis R, Greenberg M . Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science. 1995; 270(5240):1326-31. DOI: 10.1126/science.270.5240.1326. View

Chen J, Chou C . Acrylamide inhibits cellular differentiation of human neuroblastoma and glioblastoma cells. Food Chem Toxicol. 2015; 82:27-35. DOI: 10.1016/j.fct.2015.04.030. View

Belayev L, Busto R, Zhao W, Ginsberg M . Quantitative evaluation of blood-brain barrier permeability following middle cerebral artery occlusion in rats. Brain Res. 1996; 739(1-2):88-96. DOI: 10.1016/s0006-8993(96)00815-3. View

Kim E, Choi E . Compromised MAPK signaling in human diseases: an update. Arch Toxicol. 2015; 89(6):867-82. DOI: 10.1007/s00204-015-1472-2. View

10.

Uthra C, Shrivastava S, Jaswal A, Sinha N, Reshi M, Shukla S . Therapeutic potential of quercetin against acrylamide induced toxicity in rats. Biomed Pharmacother. 2017; 86:705-714. DOI: 10.1016/j.biopha.2016.12.065. View

11.

Kim K, Park B, Rhee D, Pyo S . Acrylamide Induces Senescence in Macrophages through a Process Involving ATF3, ROS, p38/JNK, and a Telomerase-Independent Pathway. Chem Res Toxicol. 2014; 28(1):71-86. DOI: 10.1021/tx500341z. View

12.

Pedraza L, Fidler L, Staugaitis S, Colman D . The active transport of myelin basic protein into the nucleus suggests a regulatory role in myelination. Neuron. 1997; 18(4):579-89. DOI: 10.1016/s0896-6273(00)80299-8. View

13.

Bakathir H, Abbas N . Detection of the antibacterial effect of Nigella sativa ground seeds with water. Afr J Tradit Complement Altern Med. 2012; 8(2):159-64. PMC: 3252685. DOI: 10.4314/ajtcam.v8i2.63203. View

14.

Carpentier A, Canney M, Vignot A, Reina V, Beccaria K, Horodyckid C . Clinical trial of blood-brain barrier disruption by pulsed ultrasound. Sci Transl Med. 2016; 8(343):343re2. DOI: 10.1126/scitranslmed.aaf6086. View

15.

Mehri S, Karami H, Hassani F, Hosseinzadeh H . Chrysin reduced acrylamide-induced neurotoxicity in both in vitro and in vivo assessments. Iran Biomed J. 2014; 18(2):101-6. PMC: 3933919. DOI: 10.6091/ibj.1291.2013. View

16.

Beker M, Dalli T, Elibol B . Thymoquinone Can Improve Neuronal Survival and Promote Neurogenesis in Rat Hippocampal Neurons. Mol Nutr Food Res. 2017; 62(5). DOI: 10.1002/mnfr.201700768. View

17.

Hosseinzadeh H, Parvardeh S . Anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, in mice. Phytomedicine. 2004; 11(1):56-64. DOI: 10.1078/0944-7113-00376. View

18.

Hosseinzadeh H, Parvardeh S, Nassiri Asl M, Sadeghnia H, Ziaee T . Effect of thymoquinone and Nigella sativa seeds oil on lipid peroxidation level during global cerebral ischemia-reperfusion injury in rat hippocampus. Phytomedicine. 2007; 14(9):621-7. DOI: 10.1016/j.phymed.2006.12.005. View

19.

Sofroniew M, Vinters H . Astrocytes: biology and pathology. Acta Neuropathol. 2009; 119(1):7-35. PMC: 2799634. DOI: 10.1007/s00401-009-0619-8. View

20.

Cobourne-Duval M, Taka E, Mendonca P, Bauer D, Soliman K . The Antioxidant Effects of Thymoquinone in Activated BV-2 Murine Microglial Cells. Neurochem Res. 2016; 41(12):3227-3238. PMC: 5116410. DOI: 10.1007/s11064-016-2047-1. View