Skip to main content

Advertisement

SpringerLink
Log in

Neuroprotective effects of gallic acid against neurotoxicity induced by sodium arsenite in rats

  • Original Article
  • Published:
Comparative Clinical Pathology Aims and scope Submit manuscript

Abstract

Arsenic causes a wide range of neurological complications including cognitive impairment, short-term memory and concentration problems. The present study investigated effects of gallic acid (GA) against sodium arsenite (SA)-induced neurotoxicity in rats. Thirty-five adult male rats were randomly divided into five groups. Group 1 received normal saline (2 ml/kg, P.O.) for 21 days. Group 2 received SA (10 mg/kg, P.O., for 14 days). Groups 3 and 4 received GA (10 and 30 mg/kg, P.O., respectively) for 7 consecutive days prior to SA treatment and continued up to 21 days, parallel to SA administration. Group 5 received GA (30 mg/kg, P.O.) for 21 days. The long-term memory, motor performance, locomotor activity, and behavioral parameters were evaluated. The activity of glutathione peroxidase (GPx) and the level of MDA and glutathione (GSH) were measured in hippocampus, corpus striatum, and cortex of brains of rats. Histopathological parameters were also assessed. GA significantly reversed SA-induced reduction of step-through latency, latency to fall, and crossing, rearing, and grooming activity. GA significantly decreased SA-induced increased MDA level, and decreased GSH level and GPx activity in different parts of brain. Our results suggest that GA enhances endogenous antioxidant activity contributing to the improvement of SA-induced neural and behavioral dysfunction.

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

Similar content being viewed by others

References

  • Aliyu M, Ibrahim S, Inuwa HM, Sallau AB, Abbas O, Aimola IA et al (2013) Ameliorative effects of acacia honey against sodium arsenite-induced oxidative stress in some viscera of male Wistar albino rats. Biochem Res Int 2013

  • Apel K, Hirt H (2004) Reactive oxygen species: metabolism, oxidative stress, and signal transduction. Annu Rev Plant Biol 55:373–399

    Article  CAS  PubMed  Google Scholar 

  • Asnaashari M, Farhoosh R, Sharif A (2014) Antioxidant activity of gallic acid and methyl gallate in triacylglycerols of Kilka fish oil and its oil-in-water emulsion. Food Chem 159:439–444

    Article  CAS  PubMed  Google Scholar 

  • Ataie A, Sabetkasaei M, Haghparast A, Moghaddam AH, Ataie R, Moghaddam SN (2010) An investigation of the neuroprotective effects of Curcumin in a model of Homocysteine-induced oxidative stress in the rat’s brain. Daru: journal of Faculty of Pharmacy, Tehran University of Medical Sciences 18(2):128

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bashandy SA, El Awdan SA, Ebaid H, Alhazza IM (2016) Antioxidant potential of Spirulina platensis mitigates oxidative stress and reprotoxicity induced by sodium arsenite in male rats. Oxidative Med Cell Longev 2016

  • Bhattacharya S, Haldar PK (2012) Ameliorative effect Trichosanthes dioica root against arsenic-induced brain toxicity in albino rats. Toxicol Environ Chem 94(4):769–778

    Article  CAS  Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72(1–2):248–254

    Article  CAS  PubMed  Google Scholar 

  • Buchet J-P, Lauwerys R (1988) Role of thiols in the in-vitro methylation of inorganic arsenic by rat liver cytosol. Biochem Pharmacol 37(16):3149–3153

    Article  CAS  PubMed  Google Scholar 

  • Choi K-C, Lee Y-H, Jung MG, Kwon SH, Kim M-J, Jun WJ, Lee J, Lee JM, Yoon HG (2009) Gallic acid suppresses lipopolysaccharide-induced nuclear factor-κB signaling by preventing RelA acetylation in A549 lung cancer cells. Mol Cancer Res 7(12):2011–2021

    Article  CAS  PubMed  Google Scholar 

  • Chowdhury R, Dutta A, Chaudhuri SR, Sharma N, Giri AK, Chaudhuri K (2008) In vitro and in vivo reduction of sodium arsenite induced toxicity by aqueous garlic extract. Food Chem Toxicol 46(2):740–751

    Article  CAS  PubMed  Google Scholar 

  • Constant J (1997) Alcohol, ischemic heart disease, and the French paradox. Clin Cardiol 20(5):420–424

    Article  CAS  PubMed  Google Scholar 

  • Dani SU, Walter GF (2018) Chronic arsenic intoxication diagnostic score (CAsIDS). J Appl Toxicol 38(1):122–144

    Article  CAS  PubMed  Google Scholar 

  • Ercal N, Gurer-Orhan H, Aykin-Burns N (2001) Toxic metals and oxidative stress part I: mechanisms involved in metal-induced oxidative damage. Curr Top Med Chem 1(6):529–539

    Article  CAS  PubMed  Google Scholar 

  • Finsterer J, Ohnsorge P (2013) Influence of mitochondrion-toxic agents on the cardiovascular system. Regul Toxicol Pharmacol 67(3):434–445

    Article  CAS  PubMed  Google Scholar 

  • Flora SJ (2011) Arsenic-induced oxidative stress and its reversibility. Free Radic Biol Med 51(2):257–281

    Article  CAS  PubMed  Google Scholar 

  • Flora SJ, Pachauri V (2010) Chelation in metal intoxication. Int J Environ Res Public Health 7(7):2745–2788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ghaznavi H, Fatemi I, Kalantari H, Hosseini Tabatabaei SMT, Mehrabani M, Gholamine B et al (2017) Ameliorative effects of gallic acid on gentamicin-induced nephrotoxicity in rats. J Asian Nat Prod Res:1–12

  • Gholamine B, Houshmand G, Hosseinzadeh A, Kalantar M, Mehrzadi S, Goudarzi M (2019) Gallic acid ameliorates sodium arsenite-induced renal and hepatic toxicity in rats. Drug Chem Toxicol:1–12

  • Goudarzi M, Amiri S, Nesari A, Hosseinzadeh A, Mansouri E, Mehrzadi S (2018a) The possible neuroprotective effect of ellagic acid on sodium arsenate-induced neurotoxicity in rats. Life Sci 198:38–45

    Article  CAS  PubMed  Google Scholar 

  • Goudarzi M, Fatemi I, Siahpoosh A, Sezavar SH, Mansouri E, Mehrzadi S (2018b) Protective effect of ellagic acid against sodium arsenite-induced cardio-and hematotoxicity in rats. Cardiovasc Toxicol 18(4):337–345

    Article  CAS  PubMed  Google Scholar 

  • Hosseinzadeh A, Houshmand G, Goudarzi M, Sezavar SH, Mehrzadi S, Mansouri E, et al.( 2018) Ameliorative effect of gallic acid on sodium arsenite-induced spleno-, cardio-and hemato-toxicity in rats. Life sciences.

  • Kadirvel R, Sundaram K, Mani S, Samuel S, Elango N, Panneerselvam C (2007) Supplementation of ascorbic acid and α-tocopherol prevents arsenic-induced protein oxidation and DNA damage induced by arsenic in rats. Human & experimental toxicology. 26(12):939–946

    Article  CAS  Google Scholar 

  • Kim MJ, Seong AR, Yoo JY, Jin CH, Lee YH, Kim YJ, Lee J, Jun WJ, Yoon HG (2011) Gallic acid, a histone acetyltransferase inhibitor, suppresses β-amyloid neurotoxicity by inhibiting microglial-mediated neuroinflammation. Mol Nutr Food Res 55(12):1798–1808

    Article  CAS  PubMed  Google Scholar 

  • Korani MS, Farbood Y, Sarkaki A, Fathi Moghaddam H, Taghi MM (2014) Protective effects of gallic acid against chronic cerebral hypoperfusion-induced cognitive deficit and brain oxidative damage in rats. Eur J Pharmacol 733:62–67

    Article  CAS  PubMed  Google Scholar 

  • Lemarie A, Bourdonnay E, Morzadec C, Fardel O, Vernhet L (2008) Inorganic arsenic activates reduced NADPH oxidase in human primary macrophages through a Rho kinase/p38 kinase pathway. J Immunol 180(9):6010–6017

    Article  CAS  PubMed  Google Scholar 

  • Leslie EM, Haimeur A, Waalkes MP (2004) Arsenic transport by the human multidrug resistance protein 1 (MRP1/ABCC1) evidence that a tri-glutathione conjugate is required. J Biol Chem 279(31):32700–32708

    Article  CAS  PubMed  Google Scholar 

  • Liu SX, Athar M, Lippai I, Waldren C, Hei TK (2001) Induction of oxyradicals by arsenic: implication for mechanism of genotoxicity. Proc Natl Acad Sci 98(4):1643–1648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu T-H, Su C-C, Chen Y-W, Yang C-Y, Wu C-C, Hung D-Z, Chen CH, Cheng PW, Liu SH, Huang CF (2011) Arsenic induces pancreatic β-cell apoptosis via the oxidative stress-regulated mitochondria-dependent and endoplasmic reticulum stress-triggered signaling pathways. Toxicol Lett 201(1):15–26

    Article  CAS  PubMed  Google Scholar 

  • Mansouri MT, Naghizadeh B, Ghorbanzadeh B, Farbood Y, Sarkaki A, Bavarsad K (2013a) Gallic acid prevents memory deficits and oxidative stress induced by intracerebroventricular injection of streptozotocin in rats. Pharmacol Biochem Behav 111:90–96

    Article  CAS  PubMed  Google Scholar 

  • Mansouri MT, Farbood Y, Sameri MJ, Sarkaki A, Naghizadeh B, Rafeirad M (2013b) Neuroprotective effects of oral gallic acid against oxidative stress induced by 6-hydroxydopamine in rats. Food Chem 138(2):1028–1033

    Article  CAS  PubMed  Google Scholar 

  • Maurya H, Mangal V, Gandhi S, Prabhu K, Ponnudurai K (2014) Prophylactic antioxidant potential of gallic acid in murine model of sepsis. Int J Inflamm 2014

  • Mehrzadi S, Fatemi I, Malayeri AR, Khodadadi A, Mohammadi F, Mansouri E, et al (2018) Ellagic acid mitigates sodium arsenite-induced renal and hepatic toxicity in male Wistar rats. Pharmacological Reports 70:712-719

  • Mishima K, Egashira N, Hirosawa N, Fujii M, Matsumoto Y, Iwasaki K, Fujiwara M (2001) Characteristics of learning and memory impairment induced by Δ9-tetrahydrocannabinol in rats. The Japanese journal of pharmacology 87(4):297–308

    Article  CAS  PubMed  Google Scholar 

  • Mishra D, Flora S (2008) Differential oxidative stress and DNA damage in rat brain regions and blood following chronic arsenic exposure. Toxicol Ind Health 24(4):247–256

    Article  CAS  PubMed  Google Scholar 

  • Mittal M, Flora S (2007) Vitamin E supplementation protects oxidative stress during arsenic and fluoride antagonism in male mice. Drug Chem Toxicol 30(3):263–281

    Article  CAS  PubMed  Google Scholar 

  • Mo J, Xia Y, Wade TJ, Schmitt M, Le XC, Dang R et al (2006) Chronic arsenic exposure and oxidative stress: OGG1 expression and arsenic exposure, nail selenium, and skin hyperkeratosis in Inner Mongolia. Environ Health Perspect:835–841

  • Monville C, Torres EM, Dunnett SB (2006) Comparison of incremental and accelerating protocols of the rotarod test for the assessment of motor deficits in the 6-OHDA model. J Neurosci Methods 158(2):219–223

    Article  PubMed  Google Scholar 

  • Nabavi SF, Habtemariam S, Jafari M, Sureda A, Nabavi SM (2012) Protective role of gallic acid on sodium fluoride induced oxidative stress in rat brain. Bull Environ Contam Toxicol 89(1):73–77

    Article  CAS  PubMed  Google Scholar 

  • Ng JC, Wang J, Shraim A (2003) A global health problem caused by arsenic from natural sources. Chemosphere 52(9):1353–1359

    Article  CAS  PubMed  Google Scholar 

  • Nikaido M, Pi J, Kumagai Y, Yamauchi H, Taguchi K, Horiguchi S, Sun Y, Sun G, Shimojo N (2003) Decreased enzyme activity of hepatic thioredoxin reductase and glutathione reductase in rabbits by prolonged exposure to inorganic arsenate. Environ Toxicol 18(5):306–311

    Article  CAS  PubMed  Google Scholar 

  • Oyagbemi A, Omobowale T, Saba A, Adedara I, Olowu E, Akinrinde A, Dada RO (2016) Gallic acid protects against cyclophosphamide-induced toxicity in testis and epididymis of rats. Andrologia 48(4):393–401

    Article  CAS  PubMed  Google Scholar 

  • Padma VV, Sowmya P, Felix TA, Baskaran R, Poornima P (2011) Protective effect of gallic acid against lindane induced toxicity in experimental rats. Food Chem Toxicol 49(4):991–998

    Article  CAS  Google Scholar 

  • Prakash C, Soni M, Kumar V (2015) Biochemical and molecular alterations following arsenic-induced oxidative stress and mitochondrial dysfunction in rat brain. Biol Trace Elem Res 167(1):121–129

    Article  CAS  PubMed  Google Scholar 

  • Prince PSM, Kumar M, Selvakumari C (2011) Effects of gallic acid on brain lipid peroxide and lipid metabolism in streptozotocin-induced diabetic Wistar rats. J Biochem Mol Toxicol 25(2):101–107

    Article  CAS  Google Scholar 

  • Radabaugh TR, Aposhian HV (2000) Enzymatic reduction of arsenic compounds in mammalian systems: reduction of arsenate to arsenite by human liver arsenate reductase. Chem Res Toxicol 13(1):26–30

    Article  CAS  PubMed  Google Scholar 

  • Ramanathan K, Balakumar B, Panneerselvam C (2002) Effects of ascorbic acid and a-tocopherol on arsenic-induced oxidative stress. Human & experimental toxicology 21(12):675–680

    Article  CAS  Google Scholar 

  • Ramanathan K, Anusuyadevi M, Shila S, Panneerselvam C (2005) Ascorbic acid and α-tocopherol as potent modulators of apoptosis on arsenic induced toxicity in rats. Toxicol Lett 156(2):297–306

    Article  CAS  PubMed  Google Scholar 

  • Rasool MK, Sabina EP, Ramya SR, Preety P, Patel S, Mandal N, Mishra PP, Samuel J (2010) Hepatoprotective and antioxidant effects of gallic acid in paracetamol-induced liver damage in mice. J Pharm Pharmacol 62(5):638–643

    Article  CAS  PubMed  Google Scholar 

  • Reckziegel P, Dias VT, Benvegnú D, Boufleur N, Silva Barcelos RC, Segat HJ, Pase CS, Dos Santos CM, Flores EM, Bürger ME (2011) Locomotor damage and brain oxidative stress induced by lead exposure are attenuated by gallic acid treatment. Toxicol Lett 203(1):74–81

    Article  CAS  PubMed  Google Scholar 

  • Reckziegel P, Dias VT, Benvegnú DM, Boufleur N, Barcelos RCS, Segat HJ, Pase CS, Dos Santos CMM, Flores ÉMM, Bürger ME (2016) Antioxidant protection of gallic acid against toxicity induced by Pb in blood, liver and kidney of rats. Toxicol Rep 3:351–356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roby MHH, Sarhan MA, Selim KA-H, Khalel KI (2013) Evaluation of antioxidant activity, total phenols and phenolic compounds in thyme (Thymus vulgaris L.), sage (Salvia officinalis L.), and marjoram (Origanum majorana L.) extracts. Ind Crop Prod 43:827–831

    Article  CAS  Google Scholar 

  • Rodrıguez V, Carrizales L, Jimenez-Capdeville M, Dufour L, Giordano M (2001) The effects of sodium arsenite exposure on behavioral parameters in the rat. Brain Res Bull 55(2):301–308

    Article  PubMed  Google Scholar 

  • Rodrı́guez VM, Carrizales L, Jiménez-Capdeville ME, Dufour L, Giordano M (2001) The effects of sodium arsenite exposure on behavioral parameters in the rat. Brain Res Bull 55(2):301–308

    Article  PubMed  Google Scholar 

  • Rodriguez VM, Del Razo LM, Limon-Pacheco JH, Giordano M, Sanchez-Pena LC, Uribe-Querol E et al (2005) Glutathione reductase inhibition and methylated arsenic distribution in Cd1 mice brain and liver. Toxicological sciences : an official journal of the Society of Toxicology 84(1):157–166

    Article  CAS  Google Scholar 

  • Safaei F, Mehrzadi S, Khadem Haghighian H, Hosseinzadeh A, Nesari A, Dolatshahi M et al (2017) Protective effects of gallic acid against methotrexate-induced toxicity in rats. Acta Chir Belg:1–9

  • Samikkannu T, Chen C-H, Yih L-H, Wang AS, Lin S-Y, Chen T-C, Jan KY (2003) Reactive oxygen species are involved in arsenic trioxide inhibition of pyruvate dehydrogenase activity. Chem Res Toxicol 16(3):409–414

    Article  CAS  PubMed  Google Scholar 

  • Samuel S, Kathirvel R, Jayavelu T, Chinnakkannu P (2005) Protein oxidative damage in arsenic induced rat brain: influence of dl-α-lipoic acid. Toxicol Lett 155(1):27–34

    Article  CAS  PubMed  Google Scholar 

  • Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25:192–205

    Article  CAS  PubMed  Google Scholar 

  • Sharma M, Gupta Y (2001) Effect of chronic treatment of melatonin on learning, memory and oxidative deficiencies induced by intracerebroventricular streptozotocin in rats. Pharmacol Biochem Behav 70(2):325–331

    Article  CAS  PubMed  Google Scholar 

  • Shila S, Subathra M, Devi MA, Panneerselvam C (2005) Arsenic intoxication-induced reduction of glutathione level and of the activity of related enzymes in rat brain regions: reversal by dl-α-lipoic acid. Arch Toxicol 79(3):140–146

    Article  CAS  PubMed  Google Scholar 

  • Yadav RS, Sankhwar ML, Shukla RK, Chandra R, Pant AB, Islam F, Khanna VK (2009) Attenuation of arsenic neurotoxicity by curcumin in rats. Toxicol Appl Pharmacol 240(3):367–376

    Article  CAS  PubMed  Google Scholar 

  • Yadav RS, Shukla RK, Sankhwar ML, Patel DK, Ansari RW, Pant AB, Islam F, Khanna VK (2010) Neuroprotective effect of curcumin in arsenic-induced neurotoxicity in rats. Neurotoxicology 31(5):533–539

    Article  CAS  PubMed  Google Scholar 

  • Yamanaka K, Hasegawa A, Sawamura R, Okada S (1991) Cellular response to oxidative damage in lung induced by the administration of dimethylarsinic acid, a major metabolite of inorganic arsenics, in mice. Toxicol Appl Pharmacol 108(2):205–213

    Article  CAS  PubMed  Google Scholar 

  • Yedjou CG, Rogers C, Brown E, Tchounwou PB (2008) Differential effect of ascorbic acid and n-acetyl-l-cysteine on arsenic trioxide-mediated oxidative stress in human leukemia (HL-60) cells. J Biochem Mol Toxicol 22(2):85–92

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yen Y-P, Tsai K-S, Chen Y-W, Huang C-F, Yang R-S, Liu S-H (2012) Arsenic induces apoptosis in myoblasts through a reactive oxygen species-induced endoplasmic reticulum stress and mitochondrial dysfunction pathway. Arch Toxicol 86(6):923–933

    Article  CAS  PubMed  Google Scholar 

  • Yousef MI, El-Demerdash FM, Radwan FM (2008) Sodium arsenite induced biochemical perturbations in rats: ameliorating effect of curcumin. Food Chem Toxicol 46(11):3506–3511

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by Deputy of Research of Jundishapur University of Medical Sciences of Ahvaz, Iran (Grant No. 94S138).

Author information

Authors and Affiliations

  1. Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran

    Azam Hosseinzadeh & Saeed Mehrzadi

  2. Department of Pharmacology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Gholamreza Houshmand

  3. Shoushtar Faculty of Medical Sciences, Shoushtar, Iran

    Mojtaba Kalantar

  4. Department of Pharmacology, School of Pharmacy|, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Hamid Reza Khalili

  5. Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Mehdi Goudarzi

Authors
  1. Azam Hosseinzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gholamreza Houshmand
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mojtaba Kalantar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hamid Reza Khalili
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Saeed Mehrzadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mehdi Goudarzi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mehdi Goudarzi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Ethical approval

The investigation was performed according to the Animal Ethics Committee Guidelines for the use of experimental animals (Ethic code IR.AJUMS.REC.1395.28).

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hosseinzadeh, A., Houshmand, G., Kalantar, M. et al. Neuroprotective effects of gallic acid against neurotoxicity induced by sodium arsenite in rats. Comp Clin Pathol 29, 621–629 (2020). https://doi.org/10.1007/s00580-020-03097-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00580-020-03097-w

Keywords

Search

Navigation