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Effects of Glycyrrhetinic Acid on GSH Synthesis Induced by Realgar in the Mouse Hippocampus: Involvement of System \( {\mathbf{X}}_{{\mathbf{AG}}^{-}} \), System \( {\mathbf{X}}_{{\mathbf{C}}^{-}} \), MRP-1, and Nrf2

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Abstract

Realgar, a type of mineral drug-containing arsenic, exhibits neurotoxicity. Brain glutathione (GSH) is crucial to protect the nervous system and to resist arsenic toxicity. Therefore, the main aim of this study was to explore the neurotoxic mechanisms of realgar and the protective effects of glycyrrhetinic acid (GA) by observing the effects of GA on the hippocampal GSH biosynthetic pathway after exposure to realgar. Institute of Cancer Research (ICR) mice were randomly divided into five groups: a control group, a GA control group, a realgar alone group, a low-dose GA intervention group, and a high-dose GA intervention group. Cognitive ability was tested using an object recognition task (ORT). The ultrastructures of the hippocampal neurons and synapses were observed. mRNA and protein levels of EAAT1, EAAT2, EAAT3, xCT, Nrf2, HO-1, γ-GCS (GCLC, GCLM), and MRP-1 were measured, as was the cellular localization of EAAT3, xCT, MRP-1, and Nrf2. The levels of GSH in the hippocampus, the levels of glutamate (Glu) and cysteine (Cys) in the extracellular fluid of hippocampal CA1 region, and the levels of active sulfur in the brain were also investigated. The results indicate that realgar lowered hippocampal GSH levels, resulting in ultrastructural changes in hippocampal neurons and synapses and deficiencies in cognitive ability, ultimately inducing neurotoxicity. GA could trigger the expression of Nrf2, HO-1, EAAT1, EAAT2, EAAT3, xCT, MRP-1, GCLC, and GCLM. Additionally, the expression of γ-GT and the supply levels of Glu and Cys increased, ultimately causing a significant increase in hippocampal GSH to alleviate realgar-induced neurotoxicity. In conclusion, the findings from our study indicate that GA can antagonize decreased brain GSH levels induced by realgar and can lessen the neurotoxicity of realgar.

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Abbreviations

GA:

Glycyrrhetinic acid

GSH:

Glutathione

ICR:

Institute of cancer research

TCMs:

Traditional Chinese medicines

BBB:

Blood–brain barrier

ORT:

Object recognition task

γ-GCS:

γ-Glutamylcysteine synthetase

EAAT:

Excitatory amino acid transporter

Glu:

Glutamate

Cys:

Cysteine

Gly:

Glycine

Cys2 :

Cystine

MRP-1:

Multidrug resistance-associated protein 1

γ-GT:

γ-Glutamyl transpeptidase

CMC-Na:

Sodium carboxymethylcellulose

MD:

Microdialysis

HG-FAAS:

Hydride generation flame atomic absorption spectrometry

HPLC:

High-performance liquid chromatography

References

  1. Li C, Liang A, Wang J, Xue B, Li H, Yang B, Wang J, Xie Q, Nilsen OG, Zhang B (2011) Arsenic accumulation following realgar administration in rats. Zhongguo Zhong Yao Za Zhi 36(14):1895–1900

    PubMed  Google Scholar 

  2. Sun G (2014) Arsenic contamination and arsenicosis in China. Toxicol Appl Pharmacol 198(3):268–271. doi:10.1016/j.taap.2003.10.017

    Article  Google Scholar 

  3. von Ehrenstein OS, Poddar S, Yuan Y, Mazumder DG, Eskenazi B, Basu A, Hira-Smith M, Ghosh N, Lahiri S, Haque R, Ghosh A, Kalman D, Das S, Smith AH (2007) Children’s intellectual function in relation to arsenic exposure. Epidemiology 18(1):44–51

    Article  Google Scholar 

  4. Wasserman GA, Liu X, Parvez F, Factor-Litvak P, Ahsan H, Levy D, Kline J, van Geen A, Mey J, Slavkovich V, Siddique AB, Islam T, Graziano JH (2011) Arsenic and manganese exposure and children’s intellectual function. Neurotoxicology 32(4):450–457. doi:10.1016/j.neuro.2011.03.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Cronican AA, Fitz NF, Carter A, Saleem M, Shiva S, Barchowsky A, Koldamova R, Schug J, Lefterov I (2013) Genome-wide alteration of histone H3K9 acetylation pattern in mouse offspring prenatally exposed to arsenic. PLoS One 8(2):e53478. doi:10.1371/journal.pone.0053478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Krüger K, Straub H, Hirner AV, Hippler J, Binding N, Musshoff U (2009) Effects of monomethylarsonic and monomethylarsonous acid on evoked synaptic potentials in hippocampal slices of adult and young rats. Toxicol Appl Pharmacol 236(1):115–123. doi:10.1016/j.taap.2008.12.025

    Article  PubMed  Google Scholar 

  7. Huo TG, Li WK, Zhang YH, Yuan J, Gao LY, Yuan Y, Yang HL, Jiang H, Sun GF (2015) Excitotoxicity induced by realgar in the rat hippocampus: the involvement of learning memory injury, dysfunction of glutamate metabolism and NMDA receptors. Mol Neurobiol 51(3):980–994. doi:10.1007/s12035-014-8753-2

    Article  CAS  PubMed  Google Scholar 

  8. Ming LJ, Yin AC (2013) Therapeutic effects of glycyrrhizic acid. Nat Prod Commun 8(3):415–418

    CAS  PubMed  Google Scholar 

  9. Dong J, Yan XY, Wang MY, Zhan Z (2014) Animal experimental studies on Niuhuang Jiedu Tablet compatibility affecting realgar arsenic toxicity. Lishizhen Med Mater Medica Res 2(25):317–319

    Google Scholar 

  10. Flora SJ (2011) Arsenic-induced oxidative stress and its reversibility. Free Radic Biol Med 51(2):257–281. doi:10.1016/j.freeradbiomed.2011.04.008

    Article  CAS  PubMed  Google Scholar 

  11. Wang Y, Zhao F, Jin Y, Zhong Y, Yu X, Li G, Lv X, Sun G (2011) Effects of exogenous glutathione on arsenic burden and NO metabolism in brain of mice exposed to arsenic through drinking water. Arch Toxicol 85(3):177–184. doi:10.1007/s00204-010-0573-1

    Article  CAS  PubMed  Google Scholar 

  12. Tabuchi M, Imamura S, Kawakami Z, Ikarashi Y, Kase Y (2012) The blood-brain barrier permeability of 18β-glycyrrhetinic acid, a major metabolite of glycyrrhizin in glycyrrhiza root, a constituent of the traditional Japanese medicine yokukansan. Cell Mol Neurobiol 32(7):1139–1146. doi:10.1007/s10571-012-9839-x

    Article  CAS  PubMed  Google Scholar 

  13. Oztanir MN, Ciftci O, Cetin A, Durak MA, Basak N, Akyuva Y (2014) The beneficial effects of 18β-glycyrrhetinic acid following oxidative and neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion in a C57BL/J6 mouse model. Neurol Sci 35(8):1221–1228. doi:10.1007/s10072-014-1685-9

    Article  PubMed  Google Scholar 

  14. Wang D, Guo TQ, Wang ZY, Lu JH, Liu DP, Meng QF, Xie J, Zhang XL, Liu Y, Teng LS (2014) ERKs and mitochondria-related pathways are essential for glycyrrhizic acid-mediated neuroprotection against glutamate-induced toxicity in differentiated PC12 cells. Braz J Med Biol Res 47(9):773–779. doi:10.1590/1414-431X20143760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wild AC, Moinova HR, Mulcahy RT (1999) Regulation of gamma glutamylcysteine synthetase subunit gene expression by the transcription factor Nrf2. J Biol Chem 274(47):33627–33636. doi:10.1074/jbc.274.47.33627

    Article  CAS  PubMed  Google Scholar 

  16. Robert SM, Ogunrinu-Babarinde T, Holt KT, Sontheimer H (2014) Role of glutamate transporters in redox homeostasis of the brain. Neurochem Int 73:181–191. doi:10.1016/j.neuint.2014.01.001

    Article  CAS  PubMed  Google Scholar 

  17. Danbolt NC (2001) Glutamate uptake. Prog Neurobiol 65:1–105. doi:10.1016/S0301-0082(00)00067-8

    Article  CAS  PubMed  Google Scholar 

  18. Foran E, Trotti D (2009) Glutamate transporters and the excitotoxic path to motor neuron degeneration in amyotrophic lateral sclerosis. Antioxid Redox Signal 11(7):1587–1602. doi:10.1089/ars.2009.2444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Holmseth S, Dehnes Y, Huang YH, Follin-Arbelet VV, Grutle NJ, Mylonakou MN, Plachez C, Zhou Y, Furness DN, Bergles DE, Lehre KP, Danbolt NC (2012) The density of EAAC1 (EAAT3) glutamate transporters expressed by neurons in the mammalian CNS. J Neurosci 32(17):6000–6013. doi:10.1523/JNEUROSCI.5347-11.2012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Nafia I, Re DB, Masmejean F, Melon C, Kachidian P, Kerkerian-Le Goff L, Nieoullon A, Had-Aissouni L (2008) Preferential vulnerability of mesencephalic dopamine neurons to glutamate transporter dysfunction. J Neurochem 105(2):484–496. doi:10.1111/j.1471-4159.2007.05146.x

    Article  CAS  PubMed  Google Scholar 

  21. Dringen R, Hirrlinger J (2003) Glutathione pathways in the brain. Biol Chem 384(4):505–516. doi:10.1515/BC.2003.059

    Article  CAS  PubMed  Google Scholar 

  22. Lewerenz J, Hewett SJ, Huang Y, Lambros M, Gout PW, Kalivas PW, Massie A, Smolders I, Methner A, Pergande M, Smith SB, Ganapathy V, Maher P (2013) The cystine/glutamate antiporter system x(c)(-) in health and disease: from molecular mechanisms to novel therapeutic opportunities. Antioxid Redox Signal 18(5):522–555. doi:10.1089/ars.2011.4391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Heyser CJ, Ferris JS (2013) Object exploration in the developing rat: methodological considerations. Dev Psychobiol 55(4):373–381. doi:10.1002/dev.21041

    Article  PubMed  Google Scholar 

  24. Huo T, Chang B, Zhang Y, Chen Z, Li W, Jiang H (2012) Alteration of amino acid neurotransmitters in brain tissues of immature rats treated with realgar. J Pharm Biomed Anal 57:120–124. doi:10.1016/j.jpba.2011.08.032

    Article  PubMed  Google Scholar 

  25. Yang T, Shen J (2014) Simultaneous determination of four aminothiols in human plasma by high-performance liquid chromatography (HPLC) with fluorimetric detector. Fudan Univ J Med Sci 41(5):679–684

    CAS  Google Scholar 

  26. Zhang W, Li P, Geng Q, Duan Y, Guo M, Cao Y (2014) Simultaneous determination of glutathione, cysteine, homocys-teine, and cysteinylglycine in biological fluids by ion-pairing high-performance liquid chromatography coupled with precolumn derivatization. J Agric Food Chem 62(25):5845–5852. doi:10.1021/jf5014007

    Article  CAS  PubMed  Google Scholar 

  27. Shen X, Pattillo CB, Pardue S, Bir SC, Wang R, Kevil CG (2011) Measurement of plasma hydrogen sulfide in vivo and in vitro. Free Radic Biol Med 50(9):1021–1031. doi:10.1016/j.freeradbiomed.2011.01.025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wintner EA, Deckwerth TL, Langston W, Bengtsson A, Leviten D, Hill P, Insko MA, Dumpit R, VandenEkart E, Toombs CF, Szabo C (2010) A monobromobimane-based assay to measure the pharmacokinetic profile of reactive sulphide species in blood. Br J Pharmacol 160(4):941–957. doi:10.1111/j.1476-5381.2010.00704.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wang R, Tu J, Zhang Q, Zhang X, Zhu Y, Ma W, Cheng C, Brann DW, Yang F (2013) Genistein attenuates ischemic oxidative damage and behavioral deficits via eNOS/Nrf2/HO-1 signaling. Hippocampus 23(7):634–647. doi:10.1002/hipo.22126

    Article  CAS  PubMed  Google Scholar 

  30. Liu J, Lu Y, Wu Q, Goyer RA, Waalkes MP (2008) Mineral arsenicals in traditional medicines: orpiment, realgar, and arsenolite. J Pharmacol Exp Ther 326(2):363–368. doi:10.1124/jpet.108.139543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Liang A, Li C, Wang J, Xue B, Li H, Yang B, Wang J, Xie Q, Nilsen OG (2011) Toxicity study of realgar. Zhongguo Zhong Yao Za Zhi 36(14):1889–1894

    PubMed  Google Scholar 

  32. Mizoguchi K, Kanno H, Ikarashi Y, Kase Y (2014) Specific binding and characteristics of 18β-glycyrrhetinic acid in rat brain. PLoS One 9(4):e95760. doi:10.1371/journal.pone.0095760

    Article  PubMed  PubMed Central  Google Scholar 

  33. Polyakov NE, Leshina TV, Salakhutdinov NF, Konovalova TA, Kispert LD (2006) Antioxidant and redox properties of supramolecular complexes of carotenoids with beta-glycyrrhizic acid. Free Radic Biol Med 40(10):1804–1809. doi:10.1016/j.freeradbiomed.2006.01.015

    Article  CAS  PubMed  Google Scholar 

  34. Kimura Y, Goto Y, Kimura H (2010) Hydrogen sulfide increases glutathione production and suppresses oxidative stress in mitochondria. Antioxid Redox Signal 12(1):1–13. doi:10.1089/ars.2008.2282

    Article  CAS  PubMed  Google Scholar 

  35. Sato H, Tamba M, Okuno S, Sato K, Keino-Masu K, Masu M, Bannai S (2002) Distribution of cystine/glutamate exchange transporter, system x(c)-, in the mouse brain. J Neurosci 22(18):8028–8033

    CAS  PubMed  Google Scholar 

  36. Lewerenz J, Maher P, Methner A (2012) Regulation of xCT expression and system x(c)(−) function in neuronal cells. Amino Acids 42(1):171–179. doi:10.1007/s00726-011-0862-x

    Article  CAS  PubMed  Google Scholar 

  37. La Bella V, Valentino F, Piccoli T, Piccoli F (2007) Expression and developmental regulation of the cystine/glutamate exchanger (xc−) in the rat. Neurochem Res 32(6):1081–1090. doi:10.1007/s11064-006-9277-6

    Article  PubMed  Google Scholar 

  38. Ramos-Chávez LA, Rendón-López CR, Zepeda A, Silva-Adaya D, Del Razo LM, Gonsebatt ME (2015) Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment. Front Cell Neurosci 9:21. doi:10.3389/fncel.2015.00021

    Article  PubMed  PubMed Central  Google Scholar 

  39. Lewerenz J, Maher P (2009) Basal levels of eIF2alpha phosphorylation determine cellular antioxidant status by regulating ATF4 and xCT expression. J Biol Chem 284(2):1106–1115. doi:10.1074/jbc.M807325200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Shih AY, Erb H, Sun X, Toda S, Kalivas PW, Murphy TH (2006) Cystine/glutamate exchange modulates glutathione supply for neuroprotection from oxidative stress and cell proliferation. J Neurosci 26(41):10514–10523

    Article  CAS  PubMed  Google Scholar 

  41. Rothstein JD, Martin L, Levey AI, Dykes-Hoberg M, Jin L, Wu D, Nash N, Kuncl RW (1994) Localization of neuronal and glial glutamate transporters. Neuron 13(3):713–725. doi:10.1016/0896-6273(94)90038-8

    Article  CAS  PubMed  Google Scholar 

  42. Zerangue N, Kavanaugh MP (1996) Interaction of L-cysteine with a human excitatory amino acid transporter. J Physiol 493(Pt 2):419–423. doi:10.1113/jphysiol.1996.sp021393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Aoyama K, Suh SW, Hamby AM, Liu J, Chan WY, Chen Y, Swanson RA (2006) Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. Nat Neurosci 9(1):119–126. doi:10.1038/nn1609

    Article  CAS  PubMed  Google Scholar 

  44. Lee S, Park SH, Zuo Z (2012) Effects of isoflurane on learning and memory functions of wild-type and glutamate transporter type 3 knockout mice. J Pharm Pharmacol 64(2):302–307. doi:10.1111/j.2042-7158.2011.01404.x

    Article  CAS  PubMed  Google Scholar 

  45. Cao L, Li L, Zuo Z (2012) N-acetylcysteine reverses existing cognitive impairment and increased oxidative stress in glutamate transporter type 3 deficient mice. Neuroscience 220:85–89. doi:10.1016/j.neuroscience.2012.06.044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Berman AE, Chan WY, Brennan AM, Reyes RC, Adler BL, Suh SW, Kauppinen TM, Edling Y, Swanson RA (2011) N-acetylcysteine prevents loss of dopaminergic neurons in the EAAC1−/− mouse. Ann Neurol 69(3):509–520. doi:10.1002/ana.22162

    Article  CAS  PubMed  Google Scholar 

  47. Dringen R, Kussmaul L, Gutterer JM, Hirrlinger J, Hamprecht B (1999) The glutathione system of peroxide detoxification is less efficient in neurons than in astroglial cells. J Neurochem 72(6):2523–2530. doi:10.1046/j.1471-4159.1999.0722523.x

    Article  CAS  PubMed  Google Scholar 

  48. Stipursky J, Romão L, Tortelli V, Neto VM, Gomes FC (2011) Neuron-glia signaling: Implications for astrocyte differentiation and synapse formation. Life Sci 89(15-16):524–531. doi:10.1016/j.lfs.2011.04.005

    Article  CAS  PubMed  Google Scholar 

  49. Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, Alberini CM (2011) Astrocyte-neuron lactate transport is required for long-term memory formation. Cell 144(5):810–823. doi:10.1016/j.cell.2011.02.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Dringen R, Pfeiffer B, Hamprecht B (1999) Synthesis of the antioxidant glutathione in neurons: supply by astrocytes of CysGly as precursor for neuronal glutathione. J Neurosci 19(2):562–569

    CAS  PubMed  Google Scholar 

  51. Shih AY, Johnson DA, Wong G, Kraft AD, Jiang L, Erb H, Johnson JA, Murphy TH (2003) Coordinate regulation of glutathione biosynthesis and release by Nrf2-expressing glia potently protects neurons from oxidative stress. J Neurosci 23(8):3394–3406

    CAS  PubMed  Google Scholar 

  52. Lewerenz J, Albrecht P, Tien ML, Henke N, Karumbayaram S, Kornblum HI, Wiedau-Pazos M, Schubert D, Maher P, Methner A (2009) Induction of Nrf2 and xCT are involved in the action of the neuroprotective antibiotic ceftriaxone in vitro. J Neurochem 111(2):332–343. doi:10.1111/j.1471-4159.2009.06347.x

    Article  CAS  PubMed  Google Scholar 

  53. Escartin C, Won SJ, Malgorn C, Auregan G, Berman AE, Chen PC, Déglon N, Johnson JA, Suh SW, Swanson RA (2011) Nuclear factor erythroid 2-related factor 2 facilitates neuronal glutathione synthesis by upregulating neuronal excitatory amino acid transporter 3 expression. J Neurosci 31(20):7392–7401. doi:10.1523/JNEUROSCI.6577-10.2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Harvey CJ, Thimmulappa RK, Singh A, Blake DJ, Ling G, Wakabayashi N, Fujii J, Myers A, Biswal S (2009) Nrf2-regulated glutathione recycling independent of biosynthesis is critical for cell survival during oxidative stress. Free Radic Biol Med 46(4):443–453. doi:10.1016/j.freeradbiomed.2008.10.040

    Article  CAS  PubMed  Google Scholar 

  55. Liu D, Duan X, Dong D, Bai C, Li X, Sun G, Li B (2013) Activation of the Nrf2 pathway by inorganic arsenic in human hepatocytes and the role of transcriptional repressor Bach1. Oxid Med Cell Longev 2013:984546. doi:10.1155/2013/984546

    PubMed  PubMed Central  Google Scholar 

  56. Lau A, Whitman SA, Jaramillo MC, Zhang DD (2013) Arsenic-mediated activation of the Nrf2-Keap1antioxidant pathway. J Biochem Mol Toxicol 27(2):99–105. doi:10.1002/jbt.21463

    Article  CAS  PubMed  Google Scholar 

  57. Chen S, Zou L, Li L, Wu T (2013) The protective effect of glycyrrhetinic acid on carbon tetrachloride-induced chronic liver fibrosis in mice via upregulation of Nrf2. PLoS One 8(1):e53662. doi:10.1371/journal.pone.0053662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Mahmoud AM, Al Dera HS (2015) 18β-Glycyrrhetinic acid exerts protective effects against cyclophosphamide-induced hepatotoxicity: potential role of PPARγ and Nrf2 upregulation. Genes Nutr 10(6):41. doi:10.1007/s12263-015-0491-1

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The work was financially supported by the National Natural Science Foundation of China (81473417).

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Authors and Affiliations

  1. Department of Health Laboratory Technology, School of Public health, China Medical University, Shenyang, 110122, People’s Republic of China

    Yan-lei Wang, Mo Chen, Tao-guang Huo, Ying-hua Zhang, Ying Fang, Cong Feng, Shou-yun Wang & Hong Jiang

  2. School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, 063009, People’s Republic of China

    Yan-lei Wang

  3. School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, People’s Republic of China

    Ying Fang

  4. School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, People’s Republic of China

    Shou-yun Wang

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  1. Yan-lei Wang
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Wang, Yl., Chen, M., Huo, Tg. et al. Effects of Glycyrrhetinic Acid on GSH Synthesis Induced by Realgar in the Mouse Hippocampus: Involvement of System \( {\mathbf{X}}_{{\mathbf{AG}}^{-}} \), System \( {\mathbf{X}}_{{\mathbf{C}}^{-}} \), MRP-1, and Nrf2. Mol Neurobiol 54, 3102–3116 (2017). https://doi.org/10.1007/s12035-016-9859-5

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