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The potential neuroprotective effect of allicin and melatonin in acrylamide-induced brain damage in rats

Environmental Science and Pollution Research volume 28, pages 58768–58780 (2021)Cite this article

Abstract

Acrylamide (ACR) is an unsaturated monomer that served various fields; however, it is a potent neurotoxin. The target of the present study is to explore the neuroprotective efficacy of allicin and melatonin on ACR-induced neurotoxicity. Thirty-six male adult rats were non-selectively separated into six groups: placebo, allicin (20 mg/kg b.w daily per os), melatonin (10 mg/kg b.w 3 times/week per os), ACR (50 mg/kg b.w daily per os), ACR-allicin, and ACR-melatonin at the same doses as the preceding groups. The assessment of brain biomarkers, neurotransmitters, antioxidative status, Nrf2 signaling pathway, and histopathological analyses was performed following 21 days. ACR exposure induced brain lipid and DNA oxidative damage as well as reduced the glutathione (GSH) levels. The obvious brain oxidative injuries contributed to distinct brain dysfunction that was assured by alteration of brain neurotransmitters (serotonin, dopamine, acetylcholine, and acetylcholinesterase) and pathological brain lesions. Furthermore, ACR exposure increased hydroxy deoxyguanosine (8-OHdG), tumor necrosis factor-α (TNF-α), and amyloid protein (AB1-42). Finally, the mRNA transcripts of brain Keap-1, Nrf2, and NF-kB were upregulated after ACR intoxication. Interestingly, allicin and melatonin alleviated the ACR-induced brain damage assessed by the normalization of the mentioned analyses. The present study demonstrated the protective role of both allicin and melatonin in ACR-prompted neuropathy by alleviation of redox imbalance and enhancement of neurotransmitters as well as relieving DNA damage and anti-inflammatory effect.

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Data Availability

All data analyzed during the current study are included in this published article.

Abbreviations

Ach:

Acetylcholine

AchE:

Acetylcholine esterase

ACR:

Acrylamide

ANOVA:

Analysis of variance

ARE:

Antioxidant response element

Aβ1-42:

Amyloid protein1-42

BDNF:

Brain-derived neurotrophic factor

DDS:

Diallyl disulfide

DTS:

Diallyl trisulfide

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GSH:

Reduced glutathione

GSSG:

Oxidized glutathione

Keap-1:

Kelch-like ECH-associated protein-1

MDA:

Malondialdehyde

MT:

Melatonin

NF-kB:

Nuclear factor-kappa B

nNOS:

Nitric oxide synthase

Nrf2:

Nuclear factor erythroid 2 like factor

8-OHdG:

8-Hydroxy deoxyguanosine

ROS:

Reactive oxygen species

SAC:

S-Allylcysteine

SE:

Standard error

TNF-α:

Tumor necrosis factor

TTR:

Transthyretin

References

  • Abd Elmonem HA, Ali EA (2012) Effects of junk foods on brain neurotransmitters (dopamine and serotonin) and some biochemical parameters in albino rats. Egypt J Rad Sci Applic 25(1-2):29–42

    Google Scholar 

  • Abdel-Daim MM, El-Ela FIA, Alshahrani FK, Bin-Jumah M, Al-Zharani M, Almutairi B, Alkahtani S (2020) Protective effects of thymoquinone against acrylamide-induced liver, kidney and brain oxidative damage in rats. Environ Sci Pollut Res 27(30):37709–37717

    Article  CAS  Google Scholar 

  • Abouzaid OAR, El-Sonbaty SM, Barakat WM (2017a) Effect of Acrylamide on neurotransmitters and acetylcholinesterase activity in the brain of rats: therapeutic effect of ferulic acid and selenium nanoparticles. Ann Brit Med Sci 3(1):18–25

    Google Scholar 

  • Abouzaid OAR, El-Sonbaty SM, Barakat WM (2017b) Brain derived neurotrophic factor, β amyloid, interleukin-6 and neurotransmitters in amelioration of acrylamide neurotoxicity: role of ferulic acid. Med J 33(1):199–207

    Google Scholar 

  • 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 Chem Toxicol 118:745–752

    Article  CAS  Google Scholar 

  • Agrawal R, Tyagi E, Shukla R, Nath C (2009) A study of brain insulin receptors, AChE activity and oxidative stress in rat model of ICV STZ induced dementia. Neuropharmacology 56(4):779–787

    Article  CAS  Google Scholar 

  • Ahmadi Z, Ashrafizadeh M (2019) Melatonin as a potential modulator of Nrf2. Fudament Clin Pharmacol 24(1):11–19

    Google Scholar 

  • Ahmed HH, Elmegeed GA, El-Sayed SM, Abd-Elhalim MM, Shousha WG, Shafic RW (2010) Potent neuroprotective role of novel melatonin derivatives for management of central neuropathy induced by acrylamide in rats. Eur J Med Chem 45(11):5452–5459

    Article  CAS  Google Scholar 

  • Asdaq SMB, Inamdar MN (2011) Pharmacodynamic and pharmacokinetic interactions of propranolol with garlic (Allium sativum) in rats. Evid Based Complement Alternat Med 2011:824042

    Article  Google Scholar 

  • Aydın B (2017) Effects of argan oil on the mitochondrial function, antioxidant system and the activity of NADPH- generating enzymes in acrylamide treated rat brain. Biomed Pharmacother 7:476–481

    Article  CAS  Google Scholar 

  • Bhanot A, Shri R (2010) A comparative profile of methanol extracts of Allium cepa and Allium sativum in diabetic neuropathy in mice. Pharm Res 2(6):374–384

    Google Scholar 

  • Bin-Jumah M, Abdel-Fattah A-FM, Saied EM, El-Seedi HR, Abdel-Daim MM (2021) Acrylamide-induced peripheral neuropathy: manifestations, mechanisms, and potential treatment modalities. Environ Sci Pollut Res 28:13031–13046

    Article  CAS  Google Scholar 

  • Borlinghaus J, Albrecht F, Gruhlke MC, Nwachukwu ID, Slusarenko AJ (2014) Allicin: chemistry and biological properties. Molecules 19(8):12591–12618

    Article  CAS  Google Scholar 

  • Chen YX, Li GZ, Zhang B, Xia ZY, Zhang M (2016) Molecular evaluation of herbal compounds as potent inhibitors of acetylcholinesterase for the treatment of Alzheimer’s disease. Mol Med Rep 14(1):446–452

    Article  CAS  Google Scholar 

  • Culling CF (1983) Handbook of histopathological and histochemical techniques, 3rd edn. Butterworth, London

    Google Scholar 

  • Deng Y, Zhu J, Mi C, Xu B, Jiao C, Li Y, Xu D, Liu W, Xu Z (2015) Melatonin antagonizes Mn-induced oxidative injury through the activation of Keap1–Nrf2–ARE signaling pathway in the striatum of mice. Neurotox Res 27:156–171

    Article  CAS  Google Scholar 

  • Dhingra D, Kumar V (2008) Evidences for the involvement of monoaminergic and GABAergic systems in antidepressant-like activity of garlic extract in mice. Indian J Pharm 40(4):175–179

    Article  Google Scholar 

  • Draper HH, Hadley M (1990) Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 186:421–425

    Article  CAS  Google Scholar 

  • Du J, Murphy RM (2010) Characterization of the interaction of β-amyloid with transthyretin monomers and tetramers. Biochemistry 49(38):8276–8289

    Article  CAS  Google Scholar 

  • Elhelaly AE, Al Basher G, Alfarraj S, Almeer R, Bahbah EI, Fouda MMA, Bungău SG, Aleya L, Abdel-Daim MM (2019) Protective effects of hesperidin and diosmin against acrylamide-induced liver, kidney, and brain oxidative damage in rats. Environ Sci Pollut Res 26:35151–35162

    Article  CAS  Google Scholar 

  • Ellman GL, Courtney KD, Andres-Jr V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7(2):88–95

    Article  CAS  Google Scholar 

  • Emekli-Alturfan E, Beceren A, Özer A, Demiralp ZE, Sener G, Omurtag G (2012) Protective effect of N-acetyl-L-cysteine against acrylamide-induced oxidative stress in rats. Turk J Vet Anim Sci 36:438–445

    Google Scholar 

  • Farouk SM, Gad FA, Almeer R, Abdel-Daim MM, Emam MA (2021) Exploring the possible neuroprotective and antioxidant potency of lycopene against acrylamide-induced neurotoxicity in rats' brain. Biomed Pharmacother 138:111458

    Article  CAS  Google Scholar 

  • García-Trejo EM, Arellano-Buendía AS, Argüello-García R, Loredo-Mendoza ML, García-Arroyo FE, Arellano-Mendoza MG, Castillo-Hernández MC, Guevara-Balcázar G, Tapia E, Sánchez-Lozada LG, Osorio-Alonso H (2016) Effects of allicin on hypertension and cardiac function in chronic kidney disease. Oxidative Med Cell Longev 2016:1–13

    Article  CAS  Google Scholar 

  • Ghareeb DA, Khalil AA, Elbassoumy AM, Hussien HM, Abo-Sraiaa MM (2010) Ameliorated effects of garlic (Allium sativum) on biomarkers of subchronic acrylamide hepatotoxicity and brain toxicity in rats. Toxicol Environ Chem 92(7):1357–1372

    Article  CAS  Google Scholar 

  • Griffith OW (1980) Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinyl pyridine. Anal Biochem 106:207–212

    Article  CAS  Google Scholar 

  • Gupta V, Indi S, Jagannatha R (2009) Garlic extract exhibits antiamyloidogenic activity on amyloid-beta fibrillogenesis: relevance to Alzheimer’s disease. Phytother Res 23(1):111–115

    Article  Google Scholar 

  • Haduch A, Bromek E, Wójcikowski J, Gołembiowska K, Daniel WA (2016) Melatonin supports serotonin formation by brain CYP2D. Drug Metab Dispos 44(3):445–452

    Article  Google Scholar 

  • Hasan N, Yusuf N, Toossi Z, Islam N (2006) Suppression of Mycobacterium tuberculosis induced reactive oxygen species (ROS) and TNF-a mRNA expression in human monocytes by allicin. FEBS Lett 580:2517–2522

    Article  CAS  Google Scholar 

  • Hernández-Velázquez B, Camara-Lemarroy CR, González-González JA, García-Compean D, Monreal-Robles R, Cordero-Pérez P, Muñoz-Espinosa LE (2016) Effects of melatonin on the acute inflammatory response associated with endoscopic retrograde cholangiopancreatography: a randomized, double-blind, placebo-controlled trial. Rev Gastroenterol Mex 81(3):141–148

    Google Scholar 

  • Hong Y, Nan B, Wu X, Yan H, Yuan Y (2019) Allicin alleviates acrylamide-induced oxidative stress in BRL-3A cells. Life Sci 231:116550

    Article  CAS  Google Scholar 

  • Huang CC, Chiou CH, Liu SC, Hu SL, Su CM, Tsai CH, Tang CH (2019) Melatonin attenuates TNF-α and IL-1β expression in synovial fibroblasts and diminishes cartilage degradation: implications for the treatment of rheumatoid arthritis. J Pineal Res 66(3):e12560

    Article  CAS  Google Scholar 

  • Islam N, Iqbal J, Hasan N, Fatima Z, Thakur H, Hasan N, Mahdi AA, Khan T, Bano F, Ansari IA (2008) Allicin from garlic suppresses TNF-α and augments IFN-γ expressions in monocyte cultures from patients with Vaginitis. Nature Preced 1560:1

    Google Scholar 

  • Jung HY, Lee KY, Yoo DY, Kim JW, Yoo M, Lee S, Yoon YS, Choi JH, Hwang IK (2016) Essential oils from two Allium species exert effects on cell proliferation and neuroblast differentiation in the mouse dentate gyrus by modulating brain-derived neurotrophic factor and acetylcholinesterase. BMC Complement Altern Med 16(431):1–10

    Google Scholar 

  • Jung KH, Hong S, Zheng H, Lee D, Hong S (2009) Melatonin downregulates nuclear erythroid 2-related factor 2 and nuclear factor-kappa B during prevention of oxidative liver injury in a dimethylnitrosamine model. J Pineal Res 47:173–183

    Article  CAS  Google Scholar 

  • Kahkeshani N, Saeidnia S, Abdollahi M (2015) Role of antioxidants and phytochemicals on acrylamide mitigation from food and reducing its toxicity. J Food Sci Technol 52:3169–3186

    CAS  Google Scholar 

  • Khaneghah AM, Fakhri Y, Nematollahi A, Seilani F, Vasseghian Y (2020) The concentration of acrylamide in different food products: a global systematic review, meta-analysis, and meta-regression. Food Rev Int:1–18

  • Kumar S, Chatterjee S, Kumar S (2018) Dual anti-cholinesterase activity of ajoene by in silico and in vitro studies. Phcog Res 10:225–229

    Article  CAS  Google Scholar 

  • Li B, He X, Zhuang M, Niu B, Wu C, Mu H, Tang F, Cui Y, Liu W, Zhao B, Peng S, Li G, Hua J (2018) Melatonin ameliorates busulfan-induced spermatogonial stem cell oxidative apoptosis in mouse testes. Antioxid Redox Signal 28(5):385–400

    Article  CAS  Google Scholar 

  • Li XH, Li CY, Lu JM, Tian RB, Wei J (2012) Allicin ameliorates cognitive deficits ageing-induced learning and memory deficits through enhancing of Nrf2 antioxidant signaling pathways. Neurosci Lett 514(1):46–50

    Article  CAS  Google Scholar 

  • Li CL, Liu XH, Qiao Y, Ning LN, Li WJ, Sun YS, Liu DS, Gao W, Ma CM (2020) Allicin alleviates inflammation of diabetic macroangiopathy via the Nrf2 and NF-kB pathway. Eur J Pharmacol 876:173052

    Article  CAS  Google Scholar 

  • Lin L, Huang QX, Yang SS, Chu J, Wang JZ, Tian Q (2013) Melatonin in Alzheimer's disease. Int J Mol Sci 14(7):14575–14593

    Article  CAS  Google Scholar 

  • Liu H, Mao P, Wang J, Wang T, Xie CH (2015) Allicin protects PC12 cells against 6-OHDA-induced oxidative stress and mitochondrial dysfunction via regulating mitochondrial dynamics. Cell Physiol Biochem 36(3):966–979

    Article  CAS  Google Scholar 

  • Marón FJM, Camargo AB, Manuch W (2020) Allicin pharmacology: common molecular mechanisms against neuroinflammation and cardiovascular diseases. Life Sci 249:117513

    Article  CAS  Google Scholar 

  • Melo JB, Agostinho P, Oliveira CR (2003) Involvement of oxidative stress in the enhancement of acetylcholinesterase activity induced by amyloid beta-peptide. Neurosci Res 45(1):117–127

    Article  CAS  Google Scholar 

  • Mikaili P, Maadirad S, Moloudizargari M, Aghajanshakeri S, Sarahroodi S (2013) Therapeutic uses and pharmacological properties of garlic, shallot, and their biologically active compounds. Iran J Basic Medic Sci 16(10):1031–1048

    CAS  Google Scholar 

  • Murray SM, Waddella BM, Wu C (2020) Neuron-specific toxicity of chronic acrylamide exposure in C. elegans. Neurotoxicol Teratol 77(106848):1–10

    Google Scholar 

  • Pan X, Wu X, Yan D, Peng C, Rao C, Yan H (2018) Acrylamide-induced oxidative stress and inflammatory response are alleviated by N-acetylcysteine in PC12 cells: involvement of the crosstalk between Nrf2 and NF-κB pathways regulated by MAPKs. Toxicol Lett 288:55–64

    Article  CAS  Google Scholar 

  • Pan X, Zhu L, Lu H, Wang D, Lu Q, Yan H (2015) Melatonin attenuates oxidative damage induced by acrylamide in vitro and in vivo. Oxidative Med Cell Longev 12

  • Panyod S, Wu W, Lu K, Liu C, Chu Y, Ho C, Hsiao WW, Lai Y, Chen W, Lin Y, Lin S, Wu M, Sheen L (2020) Allicin modifies the composition and function of the gut microbiota in alcoholic hepatic steatosis mice. J Agric Food Chem 68(10):3088–3098

    Article  CAS  Google Scholar 

  • Parvathi P (2018) Garlic- A Golden Wonder. Research J Pharm and Tech 11(1):393–396

    Article  Google Scholar 

  • Perkins ND (2007) Integrating cell-signalling pathways with NF-kappa B and IKK function. Nat Rev Mol Cell Biol 8:49–62

    Article  CAS  Google Scholar 

  • Rawi SM, Marie MAS, Fahmy SR, El-Abied SA (2010) Hazardous effects of acrylamide on immature male and female rats. Afr J Pharm Pharmacol 6(18):1367–1386

    Google Scholar 

  • Rifai L, Saleh FA (2020) A Review on Acrylamide in Food: Occurrence, Toxicity, and Mitigation Strategies. Int J Toxicol 39:93–102

    Article  CAS  Google Scholar 

  • Satta S, Mahmoud AM, Wilkinson FL, Yvonne Alexander M, White SJ (2017) The role of Nrf2 in cardiovascular function and disease. Oxidative Med Cell Longev 2017:9237263

    Article  CAS  Google Scholar 

  • Shinomol GK, Raghunath N, Bharath MM, Muralidhara (2013) Prophylaxis with Bacopa monnieri attenuates acrylamide induced neurotoxicity and oxidative damage via elevated antioxidant function. Cent Nerv Syst Agents Med Chem 13(1):3–12

    Article  CAS  Google Scholar 

  • Sindhu G, Nishanthi E, Sharmila R (2015) Nephroprotective effect of vanillic acid against cisplatin induced nephrotoxicity in wistar rats: a biochemical and molecular study. Environ Toxicol Pharmacol 39:392–404

    Article  CAS  Google Scholar 

  • Soliman A, Wahid A, Wahby MM, Bassiouny A (2020) Study of the possible synergistic protective effects of melatonin and pregabalin in vincristine induced peripheral neuropathy Wistar albino rats. Life Sci 244:117095

    Article  CAS  Google Scholar 

  • Tamimi LN, Al-Domi HA (2019) Allicin as antioxidant: possible mechanisms for the control of diabetes-induced atherosclerosis. Acta Scientif Nutrit Health 3(6):22–28

    Google Scholar 

  • Tamura H, Takasaki A, Taketani T, Tanabe M, Kizuka F, Lee L, Tamura I, Maekawa R, Aasada H, Yamagata Y, Sugino N (2012) The role of melatonin as an antioxidant in the follicle. J Ovar Res 5(5):5

    Article  CAS  Google Scholar 

  • Wang J, Wang Z (2006) Role of melatonin in Alzheimer-like neurodegeneration. Acta Pharmacol Sin 27(1):41–49

    Article  CAS  Google Scholar 

  • Yao X, Yan L, Yao L, Guan W, Zeng F, Cao F, Zhang Y (2014) Acrylamide exposure impairs blood-cerebrospinal fluid barrier function. Neural Regen Res 9:555–560

    Article  CAS  Google Scholar 

  • Yousef MI, El-Demerdash F (2006) Acrylamide-induced oxidative stress and biochemical perturbations in rats. Toxicology. 219:133–141

    Article  CAS  Google Scholar 

  • Zamani E, Shokrzade M, Fallah M, Shaki F (2017) A review of acrylamide toxicity and its mechanism. Pharmaceut Biomed Res 3:1–7

    Article  CAS  Google Scholar 

  • Zhang L, Wang E, Chen F, Yan H, Yuan Y (2013) Potential protective effects of oral administration of allicin on acrylamide-induced toxicity in male mice. Food Funct 4(8):1229–1236

    Article  CAS  Google Scholar 

  • Zhao M, Wang L, Hu X, Chen F, Chan L (2017) Acrylamide-induced neurotoxicity in primary astrocytes and microglia: roles of the Nrf2-ARE and NF-κB pathways. Food Chem Toxicol 106

  • Zhu JY, Zeng T, Zhu YB, Yu SF, Wang QS, Zhang LP, Guo X, Xie KQ (2008) Effect of acrylamide on the nervous tissue antioxidant system and sciatic nerve electrophysiology in rats. Nurochem Res 33:2310–2317

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Biochemistry Department, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt

    Hanan A. Edres, Nabil M. Taha, Mohamed A. Lebda & Mohamed S. Elfeky

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  1. Hanan A. Edres
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  2. Nabil M. Taha
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  3. Mohamed A. Lebda
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  4. Mohamed S. Elfeky
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Contributions

H.A.E: funding, investigation, and methodology; N.M.T: idea, design, and supervision; M.A.L: design, validation, writing the manuscript draft, manuscript revision, and editing; M.S.E: data collection and analysis, software, and visualization.

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Correspondence to Mohamed A. Lebda.

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Edres, H.A., Taha, N.M., Lebda, M.A. et al. The potential neuroprotective effect of allicin and melatonin in acrylamide-induced brain damage in rats. Environ Sci Pollut Res 28, 58768–58780 (2021). https://doi.org/10.1007/s11356-021-14800-x

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Keywords

  • Acrylamide
  • Melatonin
  • Allicin
  • Neurotransmitters
  • Oxidative stress