Skip to main content

Advertisement

Log in

Nano-curcumin versus curcumin in amelioration of deltamethrin-induced hippocampal damage

  • Original Paper
  • Published:
Histochemistry and Cell Biology Aims and scope Submit manuscript

Abstract

We aimed to prove that oxidative stress is the main mechanism responsible for hippocampal neurotoxicity induced by deltamethrin (DLM). The protective role of curcumin (CMN) and nano-curcumin (NCMN) over this toxicity was studied. The rats were categorized into four groups: control, DLM, CMN and NCMN. The study continued for 30 days. Hippocampus was processed for histological, biochemical and immunohistochemical studies. Caspase-3, glial fibrillar acidic protein (GFAP), acetylcholinesterase (AChE), malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) were measured for DLM-induced oxidative stress (increased MDA by 354%/decreased GSH by 61%, SOD by 61%, CAT 57%). Oxidative stress induced apoptosis of hippocampal neurons through increasing Nrf2, gamma-glutamyl cysteine synthetase heavy subunit (GCS-HS) and light subunit (GCS-LS) and decreasing AChE. It increases the activity of astrocytes through increasing GFAP. Finally, oxidative stress has a bad impaction on cognitive function. Improvement of oxidative stress was observed with use of CMN and NCMN (decrease of MDA/increase of GSH, SOD, CAT). The level of Nrf2, GCS-HS and GCS-LS decreased, while AChE, GFAP increased. Improvement of cognitive function was observed in both groups. In conclusion, oxidative stress is the common mechanism responsible for DLM-induced hippocampal neurotoxicity. It exerts apoptosis of hippocampal neurons through increasing Nrf2, HS-GCS, LS-GCS and decreasing AChE. In addition, it activates astrocytes through increasing expression of GFAP. The protective role of CMN and CMMN is related to their potent antioxidant effect. Much improvement has been detected with NCMN as compared to CMN.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1–3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • Adams JM, Cory S (1998) The Bcl-2 protein family: arbiters of cell survival. Science 281(5381):1322–1326

    Article  CAS  PubMed  Google Scholar 

  • Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  CAS  PubMed  Google Scholar 

  • Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB (2007) Bioavailability of curcumin: problems and promises. Mol Pharm 4(6):807–818

    Article  CAS  PubMed  Google Scholar 

  • Arisi GM (2014) Nervous and immune systems signals and connections: cytokines in hippocampus physiology and pathology. Epilepsy Behav 38:43–47

    Article  PubMed  Google Scholar 

  • Ball LM, Chhabra RS (1981) Intestinal absorption of nutrients in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). J Toxicol Environ Health 8(4):629–638

    Article  CAS  PubMed  Google Scholar 

  • Bhawana, Basniwal RK, Buttar HS, Jain VK, Jain N (2011) Curcumin nanoparticles: preparation, characterization, and antimicrobial study. J Agric Food Chem 59(5):2056–2061

    Article  CAS  PubMed  Google Scholar 

  • Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O (2012) Oxidative stress and antioxidant defense. World Allergy Organ J 5(1):9–19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Breckenridge CB, Holden L, Sturgess N, Weiner M, Sheets L, Sargent D, Soderlund DM, Choi JS, Symington S, Clark JM, Burr S, Ray D (2009) Evidence for a separate mechanism of toxicity for the Type I and the Type II pyrethroid insecticides. Neurotoxicology 30(Suppl 1):S17–S31

    Article  CAS  PubMed  Google Scholar 

  • Chance B, Schoener B, Oshino R, Itshak F, Nakase Y (1979) Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals. J Biol Chem 254(11):4764–4771

    Article  CAS  PubMed  Google Scholar 

  • Cole GM, Teter B, Frautschy SA (2007) Neuroprotective effects of curcumin. Adv Exp Med Biol 595:197–212

    Article  PubMed  PubMed Central  Google Scholar 

  • Copple IM, Goldring CE, Kitteringham NR, Park BK (2008) The Nrf2-Keap1 defence pathway: role in protection against drug-induced toxicity. Toxicology 246(1):24–33

    Article  CAS  PubMed  Google Scholar 

  • Daverey A, Agrawal SK (2016) Curcumin alleviates oxidative stress and mitochondrial dysfunction in astrocytes. Neuroscience 333:92–103

    Article  CAS  PubMed  Google Scholar 

  • de la Torre FR, Ferrari L, Salibián A (2002) Freshwater pollution biomarker: response of brain acetylcholinesterase activity in two fish species. Comp Biochem Physiol C Toxicol Pharmacol 131(3):271–280

    Article  PubMed  Google Scholar 

  • Ding R, Cao Z, Wang Y, Gao X, Luo H, Zhang C, Ma S, Ma X, Jin H, Lu C (2017) The implication of p66shc in oxidative stress induced by deltamethrin. Chem Biol Interact 278:162–169

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Frank F, Stricker T, Stallmach T, Braegger CP (2000) Helicobacter pylori infection in recurrent abdominal pain. J Pediatr Gastroenterol Nutr 31(4):424–427

    Article  CAS  PubMed  Google Scholar 

  • Gasmi S, Rouabhi R, Kebieche M, Boussekine S, Salmi A, Toualbia N, Taib C, Bouteraa Z, Chenikher H, Henine S, Djabri B (2017) Effects of Deltamethrin on striatum and hippocampus mitochondrial integrity and the protective role of Quercetin in rats. Environ Sci Pollut Res Int 24(19):16440–16457

    Article  CAS  PubMed  Google Scholar 

  • Grosse G, Thiele T, Heuckendorf E, Schopp E, Merder S, Pickert G, Ahnert-Hilger G (2002) Deltamethrin differentially affects neuronal subtypes in hippocampal primary culture. Neuroscience 112(1):233–241

    Article  CAS  PubMed  Google Scholar 

  • Guilhermino L, Celeste Lopes M, Carvalho AP, Soares AM (1996) Inhibition of acetylcholinesterase activity as effect criterion in acute tests with juvenile Daphnia magna. Chemosphere 32(4):727–738

    Article  CAS  PubMed  Google Scholar 

  • Guo L, Sun M, Xu PP, Xu YP, Lu HP, Si HY, Yan H (2008) Effects of melatonin on nerve cell apoptosis and expression of Bcl-2 & cytochrome C genes in rat cerebrum with deltamethrin induction. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 26(4):215–218

    CAS  PubMed  Google Scholar 

  • Halliwell B (1992) Reactive oxygen species and the central nervous system. J Neurochem 59(5):1609–1623

    Article  CAS  PubMed  Google Scholar 

  • Hossain MM, Suzuki T, Sato I, Takewaki T, Suzuki K, Kobayashi H (2005) Neuromechanical effects of pyrethroids, allethrin, cyhalothrin and deltamethrin on the cholinergic processes in rat brain. Life Sci 77(7):795–807

    Article  CAS  PubMed  Google Scholar 

  • Hossain MM, DiCicco-Bloom E, Richardson JR (2015) Hippocampal ER stress and learning deficits following repeated pyrethroid exposure. Toxicol Sci 143(1):220–228

    Article  CAS  PubMed  Google Scholar 

  • Hossain MM, Sivaram G, Richardson JR (2019) Regional susceptibility to ER stress and protection by salubrinal following a single exposure to deltamethrin. Toxicol Sci 167(1):249–257

    Article  CAS  PubMed  Google Scholar 

  • Huang CS, Anderson ME, Meister A (1993) Amino acid sequence and function of the light subunit of rat kidney gamma-glutamylcysteine synthetase. J Biol Chem 268(27):20578–20583

    Article  CAS  PubMed  Google Scholar 

  • Huang H, Chen X, Li D, He Y, Li Y, Du Z, Zhang K, DiPaola R, Goodin S, Zheng X (2015) Combination of α-tomatine and curcumin inhibits growth and induces apoptosis in human prostate cancer cells. PLoS ONE 10(12):e0144293

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Huang X, Liang Y, Qing Y, Chen D, Shi N (2019) Proteasome inhibition by MG-132 protects against deltamethrin-induced apoptosis in rat hippocampus. Life Sci 220:76–83

    Article  CAS  PubMed  Google Scholar 

  • Kalpana C, Menon VP (2004) Modulatory effects of curcumin on lipid peroxidation and antioxidant status during nicotine-induced toxicity. Pol J Pharmacol 56(5):581–586

    CAS  PubMed  Google Scholar 

  • Kaplowitz N, Aw TY, Ookhtens M (1985) The regulation of hepatic glutathione. Annu Rev Pharmacol Toxicol 25:715–744

    Article  CAS  PubMed  Google Scholar 

  • Kimelberg HK, Nedergaard M (2010) Functions of astrocytes and their potential as therapeutic targets. Neurotherapeutics 7(4):338–353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klaassen CD, Watkins JB, Casarett LJ (2010) Casarett & Doull’s essentials of toxicology, 2nd edn. McGraw-Hill Medical Pub. Division, New York

    Google Scholar 

  • Kocaadam B, Şanlier N (2017) Curcumin, an active component of turmeric (Curcuma longa), and its effects on health. Crit Rev Food Sci Nutr 57(13):2889–2895

    Article  CAS  PubMed  Google Scholar 

  • Kuida K, Zheng TS, Na S, Kuan C, Yang D, Karasuyama H, Rakic P, Flavell RA (1996) Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice. Nature 384(6607):368–372

    Article  CAS  PubMed  Google Scholar 

  • Li T, Shi N, Zhong YF, Dong J, Chen L, Wang B, Chen D, Wei YH, Dai ZH (2004) Effects of deltamethrin on the apoptosis and the expression of caspase-3 in rat neural cells. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 22(5):371–374

    CAS  PubMed  Google Scholar 

  • Li HY, Wu SY, Ma Q, Shi N (2011) The pesticide deltamethrin increases free radical production and promotes nuclear translocation of the stress response transcription factor Nrf2 in rat brain. Toxicol Ind Health 27(7):579–590

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li H, Wu S, Chen J, Wang B, Shi N (2013) Effect of glutathione depletion on Nrf2/ARE activation by deltamethrin in PC12 Cells. Arch Hig Rada Toksikol 64(1):87–97

    Article  CAS  Google Scholar 

  • Li J, Meng Z, Zhang G, Xing Y, Feng L, Fan S, Fan F, Buren B, Liu Q (2015) N-acetylcysteine relieves oxidative stress and protects hippocampus of rat from radiation-induced apoptosis by inhibiting caspase-3. Biomed Pharmacother 70:1–6

    Article  PubMed  CAS  Google Scholar 

  • Lu WP, Mei XT, Wang Y, Zheng YP, Xue YF, Xu DH (2015) Zn(II)-curcumin protects against oxidative stress, deleterious changes in sperm parameters and histological alterations in a male mouse model of cyclophosphamide-induced reproductive damage. Environ Toxicol Pharmacol 39(2):515–524

    Article  CAS  PubMed  Google Scholar 

  • Lu Q, Sun Y, Ares I, Anadón A, Martínez M, Martínez-Larrañaga MR, Yuan Z, Wang X, Martínez MA (2019) Deltamethrin toxicity: a review of oxidative stress and metabolism. Environ Res 170:260–281

    Article  CAS  PubMed  Google Scholar 

  • Mandal MN, Patlolla JM, Zheng L, Agbaga MP, Tran JT, Wicker L, Kasus-Jacobi A, Elliott MH, Rao CV, Anderson RE (2009) Curcumin protects retinal cells from light-and oxidant stress-induced cell death. Free Radic Biol Med 46(5):672–679

    Article  CAS  PubMed  Google Scholar 

  • Menon VP, Sudheer AR (2007) Antioxidant and anti-inflammatory properties of curcumin. Adv Exp Med Biol 595:105–125

    Article  PubMed  Google Scholar 

  • Misra HP, Fridovich I (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247(10):3170–3175

    Article  CAS  PubMed  Google Scholar 

  • Mohammadi H, Ghassemi-Barghi N, Malakshah O, Ashari S (2019) Pyrethroid exposure and neurotoxicity: a mechanistic approach. Arh Hig Rada Toksikol 70(2):74–89

    Article  CAS  PubMed  Google Scholar 

  • Moinova HR, Mulcahy RT (1998) An electrophile responsive element (EpRE) regulates beta-naphthoflavone induction of the human gamma-glutamylcysteine synthetase regulatory subunit gene. Constitutive expression is mediated by an adjacent AP-1 site. J Biol Chem 273(24):14683–14689

    Article  CAS  PubMed  Google Scholar 

  • Moinova HR, Mulcahy RT (1999) Up-regulation of the human gamma-glutamylcysteine synthetase regulatory subunit gene involves binding of Nrf-2 to an electrophile responsive element. Biochem Biophys Res Commun 261(3):661–668

    Article  CAS  PubMed  Google Scholar 

  • Muthulakshmi S, Maharajan K, Habibi HR, Kadirvelu K, Venkataramana M (2018) Zearalenone induced embryo and neurotoxicity in zebrafish model (Danio rerio): role of oxidative stress revealed by a multi biomarker study. Chemosphere 198:111–121

    Article  CAS  PubMed  Google Scholar 

  • Nguyen T, Sherratt PJ, Pickett CB (2003) Regulatory mechanisms controlling gene expression mediated by the antioxidant response element. Annu Rev Pharmacol Toxicol 43:233–260

    Article  CAS  PubMed  Google Scholar 

  • Nieradko-Iwanicka B, Borzęcki A (2015) Subacute poisoning of mice with deltamethrin produces memory impairment, reduced locomotor activity, liver damage and changes in blood morphology in the mechanism of oxidative stress. Pharmacol Rep 67(3):535–541

    Article  CAS  PubMed  Google Scholar 

  • Nunez J (2008) Morris water maze experiment. J Vis Exp 19:e897

    Google Scholar 

  • Ogaly HA, Khalaf AA, Ibrahim MA, Galal MK, Abd-Elsalam RM (2015) Influence of green tea extract on oxidative damage and apoptosis induced by deltamethrin in rat brain. Neurotoxicol Teratol 50:23–31

    Article  CAS  PubMed  Google Scholar 

  • Oltvai ZN, Milliman CL, Korsmeyer SJ (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74(4):609–619

    Article  CAS  PubMed  Google Scholar 

  • Onoue S, Takahashi H, Kawabata Y, Seto Y, Hatanaka J, Timmermann B, Yamada S (2010) Formulation design and photochemical studies on nanocrystal solid dispersion of curcumin with improved oral bioavailability. J Pharm Sci 99(4):1871–1881

    Article  CAS  PubMed  Google Scholar 

  • Porter AG, Jänicke RU (1999) Emerging roles of caspase-3 in apoptosis. Cell Death Differ 6(2):99–104

    Article  CAS  PubMed  Google Scholar 

  • Radovanović TB, Nasia M, Krizmanić II, Prokić MD, Gavrić JP, Despotović SG, Gavrilović BR, Borković-Mitić SS, Pavlović SZ, Saičić ZS (2017) Sublethal effects of the pyrethroid insecticide deltamethrin on oxidative stress parameters in green toad (Bufotes viridis L.). Environ Toxicol Chem 36(10):2814–2822

    Article  PubMed  CAS  Google Scholar 

  • Rai P, Parrish M, Tay IJ, Li N, Ackerman S, He F, Kwang J, Chow VT, Engelward BP (2015) Streptococcus pneumoniae secretes hydrogen peroxide leading to DNA damage and apoptosis in lung cells. Proc Natl Acad Sci U S A 112(26):E3421–E3430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rami A, Jansen S, Giesser I, Winckler J (2003) Post-ischemic activation of caspase-3 in the rat hippocampus: evidence of an axonal and dendritic localisation. Neurochem Int 43(3):211–223

    Article  CAS  PubMed  Google Scholar 

  • Rashid K, Sil PC (2015) Curcumin ameliorates testicular damage in diabetic rats by suppressing cellular stress-mediated mitochondria and endoplasmic reticulum-dependent apoptotic death. Biochim Biophys Acta 1852(1):70–82

    Article  CAS  PubMed  Google Scholar 

  • Ray DE (1982) Changes in brain blood flow associated with deltamethrin-induced choreoathetosis in the rat. Exp Brain Res 45(1–2):269–276

    CAS  PubMed  Google Scholar 

  • Richardson JR, Taylor MM, Shalat SL, Guillot TS, Caudle WM, Hossain MM, Mathews TA, Jones SR, Cory-Slechta DA, Miller GW (2015) Developmental pesticide exposure reproduces features of attention deficit hyperactivity disorder. FASEB J 29(5):1960–1972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Richman PG, Meister A (1975) Regulation of gamma-glutamyl-cysteine synthetase by nonallosteric feedback inhibition by glutathione. J Biol Chem 250(4):1422–1426

    Article  CAS  PubMed  Google Scholar 

  • Saillenfait AM, Ndiaye D, Sabaté JP (2015) Pyrethroids: exposure and health effects–an update. Int J Hyg Environ Health 218(3):281–292

    Article  CAS  PubMed  Google Scholar 

  • Salim S (2017) Oxidative stress and the central nervous system. J Pharmacol Exp Ther 360(1):201–205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sasaki H, Sunagawa Y, Takahashi K, Imaizumi A, Fukuda H, Hashimoto T, Wada H, Katanasaka Y, Kakeya H, Fujita M, Hasegawa K, Morimoto T (2011) Innovative preparation of curcumin for improved oral bioavailability. Biol Pharm Bull 34(5):660–665

    Article  CAS  PubMed  Google Scholar 

  • Saso L, Firuzi O (2014) Pharmacological applications of antioxidants: lights and shadows. Curr Drug Targets 15(13):1177–1199

    Article  CAS  PubMed  Google Scholar 

  • Sayeed I, Parvez S, Pandey S, Bin-Hafeez B, Haque R, Raisuddin S (2003) Oxidative stress biomarkers of exposure to deltamethrin in freshwater fish, Channa punctatus Bloch. Ecotoxicol Environ Saf 56(2):295–301

    Article  CAS  PubMed  Google Scholar 

  • Sharma P, Singh R, Jan M (2014) Dose-dependent effect of deltamethrin in testis, liver, and kidney of Wistar rats. Toxicol Int 21(2):131–139

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Suvarna SK, Layton C, Bancroft JD (2019) Bancroft’s theory and practice of histological techniques, 8th edn. Elsevier, Oxford

    Google Scholar 

  • Tipple TE, Rogers LK (2012) Methods for the determination of plasma or tissue glutathione levels. Methods Mol Biol 889:315–324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsujimoto Y (1998) Role of Bcl-2 family proteins in apoptosis: apoptosomes or mitochondria? Genes Cells 3(11):697–707

    Article  CAS  PubMed  Google Scholar 

  • Verschoyle RD, Aldridge WN (1980) Structure-activity relationships of some pyrethroids in rats. Arch Toxicol 45(4):325–329

    Article  CAS  PubMed  Google Scholar 

  • Wagner-Schuman M, Richardson JR, Auinger P, Braun JM, Lanphear BP, Epstein JN, Yolton K, Froehlic TE (2015) Association of pyrethroid pesticide exposure with attention-deficit/hyperactivity disorder in a nationally representative sample of U. S. children. Environ Health 14:44

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang Y, Bai C, Guan H, Chen R, Wang X, Wang B, Jin H, Piao F (2015) Subchronic exposure to arsenic induces apoptosis in the hippocampus of the mouse brains through the Bcl-2/Bax pathway. J Occup Health 57(3):212–221

    Article  CAS  PubMed  Google Scholar 

  • Williams MK, Rundle A, Holmes D, Reyes M, Hoepner LA, Barr DB, Camann DE, Perera FP, Whyatt RM (2008) Changes in pest infestation levels, self-reported pesticide use, and permethrin exposure during pregnancy after the 2000–2001 U.S. Environmental Protection Agency restriction of organophosphates. Environ Health Perspect 116(12):1681–1688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wolansky MJ, Harrill JA (2008) Neurobehavioral toxicology of pyrethroid insecticides in adult animals: a critical review. Neurotoxicol Teratol 30(2):55–78

    Article  CAS  PubMed  Google Scholar 

  • Wozniak DF, Olney JW, Kettinger L, Price M, Miller JP (1990) Behavioral effects of MK-801 in the rat. Psychopharmacology 101(1):47–56

    Article  CAS  PubMed  Google Scholar 

  • Wu A, Ren T, Hu Q, Liu Y (2000) Deltamethrin induces altered expression of P53, Bax and Bcl-2 in rat brain. Neurosci Lett 284(1–2):29–32

    Article  CAS  PubMed  Google Scholar 

  • Wu A, Li L, Liu Y (2003) Deltamethrin induces apoptotic cell death in cultured cerebral cortical neurons. Toxicol Appl Pharmacol 187(1):50–57

    Article  CAS  PubMed  Google Scholar 

  • Yan X, Pan B, Lv T, Liu L, Zhu J, Shen W, Huang X, Tian J (2017) Inhibition of histone acetylation by curcumin reduces alcohol-induced fetal cardiac apoptosis. J Biomed Sci 24(1):1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zamanian JL, Xu L, Foo LC, Nouri N, Zhou L, Giffard RG, Barres BA (2012) Genomic analysis of reactive astrogliosis. J Neurosci 32(18):6391–6410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu Y, Liu F, Zou X, Torbey M (2015) Comparison of unbiased estimation of neuronal number in the rat hippocampus with different staining methods. J Neurosci Methods 254:73–79

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

To all my colleagues who supported me during this work.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sherif Mohamed Zaki.

Ethics declarations

Conflict of interest

No conflict of interest.

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

Zaki, S.M., Algaleel, W.A.A., Imam, R.A. et al. Nano-curcumin versus curcumin in amelioration of deltamethrin-induced hippocampal damage. Histochem Cell Biol 154, 157–175 (2020). https://doi.org/10.1007/s00418-020-01871-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00418-020-01871-z

Keywords

Navigation