Protective effects of selenium on acrylamide-induced neurotoxicity and hepatotoxicity in rats

Document Type : Original Article


1 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

2 School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran


Objective(s): Acrylamide (ACR), has wide uses in different industries. ACR induced several toxicities including neurotoxicity and hepatotoxicity. The probable protective effects of selenium on ACR-induced neurotoxicity and hepatotoxicity in rats were evaluated.
Materials and Methods: Male Wistar rats were studied for 11 days in 8 groups: 1. Control, 2. ACR (50 mg/kg, IP), 3-5. ACR+ selenium (0.2, 0.4, 0.6 mg/kg, IP), 6. ACR+ the most effective dose of selenium (0.6 mg/kg, IP) three days after ACR administration, 7. ACR+ vitamin E (200 mg/kg IP, every other day) 8. Selenium (0.6 mg/kg IP). Finally, behavioral tests were done. The levels of malondialdehyde (MDA), glutathione (GSH), Bcl-2, Bax and caspase 3 proteins in liver and cerebral cortex tissues were measured. Also, the amount of albumin, total protein, alanine transaminase (ALT) and aspartate transaminase (AST) enzymes were determined in serum.
Results: ACR caused the severe motor impairment, increased MDA level and decreased GSH content, enhanced Bax/Bcl-2 ratio and caspase 3 proteins in brain and liver tissues. Besides, the level of AST was elevated while the total serum protein and albumin levels were decreased. Administration of selenium (0.6 mg/kg) (from the first day of the experiment and the third day) significantly recovered locomotor disorders, increased GSH content, and reduced MDA level. Also, selenium decreased Bax/Bcl-2 ratio and caspase 3 levels in brain and liver tissues.
Conclusion: The oxidative stress and apoptosis pathways have important roles in neurotoxicity and hepatotoxicity of ACR. Selenium significantly reduced ACR-induced toxicity through inhibition of oxidative stress and apoptosis.


1. Tyl RW, Friedman MA. Effects of acrylamide on rodent reproductive performance. Reprod Toxicol 2003; 17:1-13.
2. 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.
3. Kunnel SG, Subramanya S, Satapathy P, Sahoo I, Zameer F. Acrylamide induced toxicity and the propensity of phytochemicals in amelioration: a review. Cent Nerv Syst Agents Med Chem 2019; 19:100-113.
4. Kadawathagedara M, Botton J, de Lauzon-Guillain B, Meltzer HM, Alexander J, Brantsaeter AL, et al. Dietary acrylamide intake during pregnancy and postnatal growth and obesity: Results from the Norwegian Mother and Child Cohort Study (MoBa). Environ Int 2018; 113:325-334.
5. Hong Y, Nan B, Wu X, Yan H, Yuan Y. Allicin alleviates acrylamide-induced oxidative stress in BRL-3A cells. Life Sci 2019; 231:116550.
6. Tabeshpour J, Mehri S, Abnous K, Hosseinzadeh H. Neuroprotective effects of thymoquinone in acrylamide-induced peripheral nervous system toxicity through MAPKinase and apoptosis pathways in rat. Neurochem Res 2019; 44:1101-1112.
7. Tabeshpour J, Mehri S, Abnous K, Hosseinzadeh H. Role of oxidative stress, MAPKinase and apoptosis pathways in the protective effects of thymoquinone against acrylamide-induced central nervous system toxicity in rat. Neurochem Res 2020; 45:254-267.
8. Yousef M, El-Demerdash F. Acrylamide-induced oxidative stress and biochemical perturbations in rats. Toxicology 2006; 219:133-141.
9. Hogervorst JG, Baars B-J, Schouten LJ, Konings EJ, Goldbohm RA, van den Brandt PA. The carcinogenicity of dietary acrylamide intake: a comparative discussion of epidemiological and experimental animal research. Crit Rev Toxicol 2010; 40:485-512.
10. Erkekoglu P, Baydar T. Acrylamide neurotoxicity. Nutr Neurosci 2014; 17:49-57.
11. Abdel-Daim MM, Abd Eldaim MA, Hassan AG. Trigonella foenum-graecum ameliorates acrylamide-induced toxicity in rats: Roles of oxidative stress, proinflammatory cytokines, and DNA damage. Biochem Cell Biol 2015; 93:192-198.
12. Abdel-Daim MM, Abd Eldaim MA, Hassan AG. Trigonella foenum-graecum ameliorates acrylamide-induced toxicity in rats: Roles of oxidative stress, proinflammatory cytokines, and DNA damage. Biochem Cell Biol 2015; 93:192-198.
13. Bracht A, Silveira SS, Castro-Ghizoni CV, Sá-Nakanishi AB, Oliveira MRN, Bersani-Amado CA, et al. Oxidative changes in the blood and serum albumin differentiate rats with monoarthritis and polyarthritis. Springerplus 2016; 5:36-49.
14. Chen J-H, Yang C-H, Wang Y-S, Lee J-G, Cheng C-H, Chou C-C. Acrylamide-induced mitochondria collapse and apoptosis in human astrocytoma cells. Food Chem Toxicol 2013; 51:446-452.
15. Seydi E, Rajabi M, Salimi A, Pourahmad J. Involvement of mitochondrial-mediated caspase 3 activation and lysosomal labilization in acrylamide-induced liver toxicity. Toxicol Environ Chem 2015; 97:563-575.
16. Ghorbel I, Elwej A, Chaabene M, Boudawara O, Marrakchi R, Jamoussi K, et al. Effects of acrylamide graded doses on metallothioneins I and II induction and DNA fragmentation: Bochemical and histomorphological changes in the liver of adult rats. Toxicol Ind Health 2017; 33:611-622.
17. Yerlikaya FH, Yener Y. The dietary acrylamide intake adversely affects the serum trace element status. Biol Trace Elem Res 2013; 152:75-81.
18. Ikemoto T, Kunito T, Tanaka H, Baba N, Miyazaki N, Tanabe S. Detoxification mechanism of heavy metals in marine mammals and seabirds: interaction of selenium with mercury, silver, copper, zinc, and cadmium in liver. Arch Environ Contam Toxicol 2004; 47:402-413.
19. Rayman MP. The importance of selenium to human health. The lancet 2000; 356:233-241.
20. Pillai R, Uyehara‐Lock JH, Bellinger FP. Selenium and selenoprotein function in brain disorders. IUBMB life 2014; 66:229-239.
21. Ansari MA, Ahmad AS, Ahmad M, Salim S, Yousuf S, Ishrat T, et al. Selenium protects cerebral ischemia in rat brain mitochondria. Biol Trace Elem Res 2004; 101:73-86.
22. Zafar KS, Siddiqui A, Sayeed I, Ahmad M, Salim S, Islam F. Dose‐dependent protective effect of selenium in rat model of Parkinson’s disease: neurobehavioral and neurochemical evidences. J Neurochem 2003; 84:438-446.
23. Look M, Rockstroh J, Rao G, Kreuzer K, Barton S, Lemoch H, et al. Serum selenium, plasma glutathione (GSH) and erythrocyte glutathione peroxidase (GSH-Px)-levels in asymptomatic versus symptomatic human immunodeficiency virus-1 (HIV-1)-infection. Eur J Clin Nutr 1997; 51:266-272.
24. Venardos K, Harrison G, Headrick J, Perkins A. Effects of dietary selenium on glutathione peroxidase and thioredoxin reductase activity and recovery from cardiac ischemia–reperfusion. J Trace Elem Med Biol 2004; 18:81-88.
25. Gu X, Manautou JE. Molecular mechanisms underlying chemical liver injury. Expert Rev Mol Med 2012; 14:e4.
26. Ansar S, Alshehri SM, Abudawood M, Hamed SS, Ahamad T. Anti-oxidant and hepatoprotective role of selenium against silver nanoparticles. Int J Nanomedicine 2017; 12:7789-7797.
27. Wang N, Tan H-Y, Li S, Xu Y, Guo W, Feng Y. Supplementation of micronutrient selenium in metabolic diseases: Its role as an anti-oxidant. Oxid Med Cell Longev 2017; 2017.
28. Shidfar F, Faghihi A, Amiri HL, Mousavi SN. Regression of nonalcoholic fatty liver disease with zinc and selenium co-supplementation after disease progression in rats. Iran J Basic Med Sci 2018; 43:26-31.
29. Humayun Fard H, Hosseini SA, Azarbayjani MA, Nikbakht M. Antiapoptotic effects of continuous training and selenium consumption on the liver tissue of cadmium-exposed rats. Middle East j rehabil 2019;6; e91278.
30. Dominiak A, Wilkaniec A, Adamczyk A. Selenium in the therapy of neurological diseases. Where is it going? Curr Neuropharmacol 2016; 14:282-299.
31. Erbil G, Ozbal S, Sonmez U, Pekcetin C, Tugyan K, Bagriyanik A, et al. Neuroprotective effects of selenium and Ginkgo biloba extract (EGb761) against ischemia and reperfusion injury in rat brain. Neurosciences 2008; 13:233-238.
32. Cardoso BR, Roberts BR, Bush AI, Hare DJ. Selenium, selenoproteins and neurodegenerative diseases. Metallomics 2015; 7:1213-1228.
33. Adedara IA, Fabunmi AT, Ayenitaju FC, Atanda OE, Adebowale AA, Ajayi BO, et al. Neuroprotective mechanisms of selenium against arsenic-induced behavioral impairments in rats. NeuroToxicology 2020; 76:99-110.
34. LoPachin RM, Barber DS, He D, Das S. Acrylamide inhibits dopamine uptake in rat striatal synaptic vesicles. Toxicol Sci 2006; 89:224-234.
35. Mehri S, Abnous K, Khooei A, Mousavi SH, Shariaty VM, Hosseinzadeh H. Crocin reduced acrylamide-induced neurotoxicity in Wistar rat through inhibition of oxidative stress. Iran J Basic Med Sci 2015; 18:902-908.
36. Milošević MD, Paunović MG, Matić MM, Ognjanović BI, Saičić ZS. Role of selenium and vitamin C in mitigating oxidative stress induced by fenitrothion in rat liver. Biomed Pharmacother 2018; 106:232-238.
37. Chen K, Fang J, Peng X, Cui H, Chen J, Wang F, et al. Effect of selenium supplementation on aflatoxin B1-induced histopathological lesions and apoptosis in bursa of Fabricius in broilers. Food Chem Toxicol 2014; 74:91-97.
38. Zhu Y-J, Zeng T, Zhu Y-B, Yu S-F, Wang Q-S, Zhang L-P, et al. Effects of acrylamide on the nervous tissue anti-oxidant system and sciatic nerve electrophysiology in the rat. Neurochem Res 2008; 33:2310-2317.
39. Uchiyama M, Mihara M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 1978; 86:271-278.
40. Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta Gen Subj 1979; 582:67-78.
41. Sirot V, Hommet F, Tard A, Leblanc J-C. Dietary acrylamide exposure of the French population: results of the second French Total Diet Study. Food Chem Toxicol 2012; 50:889-894.
42. Li S-x, Cui N, Zhang C-l, Zhao X-l, Yu S-f, Xie K-q. Effect of subchronic exposure to acrylamide induced on the expression of bcl-2, bax and caspase 3 in the rat nervous system. Toxicology 2006; 217:46-53.
43. LoPachin RM, Gavin T. Molecular mechanism of acrylamide neurotoxicity: lessons learned from organic chemistry. Environ Health Perspect 2012; 120:1650-1657.
44. Al-Qahtani F, Arafah M, Sharma B, Siddiqi N. Effects of alpha lipoic acid on acrylamide-induced hepatotoxicity in rats. Cell Mol Biol (Noisy-le-grand) 2017; 63:1-6.
45. Rizk M, Abo-El-matty D, Aly H, Abd-Alla H, Saleh S, Younis E, et al. Therapeutic activity of sour orange albedo extract and abundant flavanones loaded silica nanoparticles against acrylamide-induced hepatotoxicity. Toxicol Rep 2018; 5:929-942.
46. Shukla PK, Khanna VK, Ali M, Maurya R, Handa S, Srimal R. Protective effect of Acorus calamus against acrylamide induced neurotoxicity. Phytother Res 2002; 16:256-260.
47. Lala V, Minter D. Liver Function Tests.[Updated 2018 Jan 12]. StatPearls [Internet] Treasure Island (FL): StatPearls Publishing 2018.
48. Mahmood SA, Amin KA, Salih SF. Effect of acrylamide on liver and kidneys in albino wistar rats. Int J Curr Microbiol App Sci 2015; 4:434-444.
49. Ahn T, Bae C-S, Yun C-H. Selenium supplementation restores the decreased albumin level of peripheral blood mononuclear cells in streptozotocin-induced diabetic mice. J Vet Sci 2016:15-0611.
50. Hamza RZ, Al-Motaani SE, Malik N. Protective and anti-oxidant role of selenium nanoparticles and vitamin C against acrylamide induced hepatotoxicity in male mice. Int J Pharmacol 2019; 15:664-674.
51. Karimani A, Hosseinzadeh H, Mehri S, Jafarian AH, Kamali SA, Hooshang Mohammadpour A, et al. Histopathological and biochemical alterations in non-diabetic and diabetic rats following acrylamide treatment. Toxin Rev 2019:1-8.
52. Özkan-Yılmaz F, Özlüer-Hunt A, Gündüz SG, Berköz M, Yalın S. Effects of dietary selenium of organic form against lead toxicity on the anti-oxidant system in Cyprinus carpio. Fish Physiol Biochem 2014; 40:355-363.
53. Abdallah EA. Potential protective role of selenium on acrylamide-induced oxidative stress in rats: A biochemical, histopathological study. Egypt J Forensic Sci 2018; 18:95-113.
54. Mendilcioglu I, Karaveli S, Erdogan G, Simsek M, Taskin O, Ozekinci M. Apoptosis and expression of Bcl-2, Bax, p53, caspase 3, and Fas, Fas ligand in placentas complicated by preeclampsia. Clin Exp Obstet Gynecol 2011; 38:38-42.
55. Kekre N, Griffin C, McNulty J, Pandey S. Pancratistatin causes early activation of caspase 3 and the flipping of phosphatidyl serine followed by rapid apoptosis specifically in human lymphoma cells. Cancer Chemother Pharmacol 2005; 56:29-38.
56. Salvesen GS, Dixit VM. Caspase activation: the induced-proximity model. Proc Natl Acad Sci U S A 1999; 96:10964-10967.
57. Guo J, Cao X, Hu X, Li S, Wang J. The anti-apoptotic, anti-oxidant and anti-inflammatory effects of curcumin on acrylamide-induced neurotoxicity in rats. BMC Pharmacology and Toxicology 2020; 21:62.
58. Karavelioglu E, Boyaci MG, Simsek N, Sonmez MA, Koc R, Karademir M, et al. Selenium protects cerebral cells by cisplatin induced neurotoxicity. Acta Cir Bras 2015; 30:394-400.
59. Zhang R, Yi R, Bi Y, Xing L, Bao J, Li J. The effect of selenium on the Cd-induced apoptosis via NO-mediated mitochondrial apoptosis pathway in chicken liver. Biol Trace Elem Res 2017; 178:310-319.
60. Siahkoohi S, Anvari M, Akhavan Tafti M, Hosseini-sharifabad M. The effects of vitamin E on the liver integrity of mice fed with acrylamide diet. Iran J Pathol 2014; 9:89-98.