Download PDF
Drug Res (Stuttg) 2015; 65(2): 65-69
DOI: 10.1055/s-0034-1372595
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Genistein Prevents Cadmium-induced Neurotoxic Effects through its Antioxidant Mechanisms

D.-k. Gong
1   Department of Neurology, Jingzhou Central Hospital, Jingzhou, Hubei Province, China
,
B.-h. Liu
1   Department of Neurology, Jingzhou Central Hospital, Jingzhou, Hubei Province, China
,
X.-h. Tan
1   Department of Neurology, Jingzhou Central Hospital, Jingzhou, Hubei Province, China
› Author Affiliations
Further Information

Publication History

received 10 February 2014

accepted 03 March 2014

Publication Date:
11 June 2014 (online)

Also available at
    Permissions and Reprints

Abstract

Introduction: Cadmium-induced neurotoxic effects are mediated through adverse oxidative stress and calcium signaling. Genistein, a phytoestrogen is a potent antioxidant and exhibits property to cross blood-brain barrier.

Methods: Experimental model of cadmium-induced neurotoxic effects were induced by treatment with cadmium (5 mg/kg) for 28 days in wistar rats. For determining the protective effect, genistein was administered at a dose of (10 mg/kg) for 7 days followed by cadmium treatment for 28 days. Serum and tissues were analyzed for various oxidative stress markers such as total antioxidant capacity, total oxidant levels, non-enzymic antioxidants, enzymic antioxidants, lipid peroxide levels and protein carbonyl content.

Results: The results showed significant increase in the oxidative stress markers during cadmium treatment was attenuated in rats treated with genistein followed by cadmium treatment. In addition, cadmium induced alterations and activities of ATPase were significantly restored by genistein treatment.

Conclusion: The present study observations show promising results of genistein against cadmium-induced neurotoxic effects in wistar rats. Thus its potent antioxidant and cytoprotective effects could act as potent therapeutic agent against various neuro-degenerative diseases involving oxidative stress as primary mechanism.

Key words

neuroprotection - ATPases - oxidative stress - genistein - cadmium
 

  • References

  • 1 Bernard A. Renal dysfunction induced by cadmium: biomarkers of critical effects. Biometals 2004; 17: 519-523
    CrossrefPubMedSearch in Google Scholar
  • 2 Jarup L, Berglund M, Elinder CG et al. Health effects of cadmium exposure – a review of the literature and a risk estimate. Scand J Work Environ Health 1998; 24: 1-51
    CrossrefPubMedSearch in Google Scholar
  • 3 Bernard A, Lauwerys R. Effects of cadmium exposure in humans. In: Handbook of experimental. Foulkes EC. (ed.). Pharmacology. Berlin: Springer-Verlag; 1986: 135-177
    CrossrefSearch in Google Scholar
  • 4 Jarup L, Hellstrom L, Alfven T et al. Low level exposure to cadmium and early kidney damage. The OSCAR study. Occup Environ Med 2000; 57: 668-672
    CrossrefPubMedSearch in Google Scholar
  • 5 Yamano T, DeCicco LA, Rikans LE. Attenuation of cadmium induced liver injury in senescent male Fischer 344 rats: role of Kupffer cells and inflammatory cytokines. Toxicol Appl Pharmacol 2000; 162: 68-75
    CrossrefPubMedSearch in Google Scholar
  • 6 Nordberg G, Jin T, Bernard A et al. Low bone density and renal dysfunction following environmental cadmium exposure in China. Ambio 2002; 31: 478-481
    PubMedSearch in Google Scholar
  • 7 Renugadevi J, Prabu SM. Naringenin protects against cadmium induced oxidative renal dysfunction in rats. Toxicology 2009; 4: 128-134
    PubMedSearch in Google Scholar
  • 8 Kousidou O, Tzanakakis GN, Karamanos NK. Effects of the natural isoflavonoid genistein on growth, signaling pathways and gene expression of matrix macromolecules by breast cancer cells. Mini Rev Med Chem 2006; 6: 331-337
    CrossrefPubMedSearch in Google Scholar
  • 9 Fuhrman B, Aviram M. Flavonoids protect LDL from oxidation and attenuate atherosclerosis. Curr Opin Lipidol 2001; 12: 41-48
    CrossrefPubMedSearch in Google Scholar
  • 10 Sribnick EA, Ray SK, Nowak MW et al. 17beta-estradiol attenuates glutamate-induced apoptosis and preserves electrophysiologic function in primary cortical neurons. J Neurosci Res 2004; 76: 688-696
    CrossrefPubMedSearch in Google Scholar
  • 11 Belevych AE, Warrier S, Harvey RD. Genistein inhibits cardiac l-type Ca2+ channel activity by a tyrosine kinase-independent mechanism. Mol Pharmacol 2002; 62: 554-565
    CrossrefPubMedSearch in Google Scholar
  • 12 Tsai TH. Concurrent measurement of unbound genistein in the blood, brain and bile of anesthetized rats using microdialysis and its pharmacokinetic application. J Chromatogr A 2005; 1073: 317-322
    CrossrefPubMedSearch in Google Scholar
  • 13 Lowry OH, Rosenbrough NJ, Farr AL et al. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265-275
    PubMedSearch in Google Scholar
  • 14 Erel O. Novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem 2004; 37: 112-119
    CrossrefPubMedSearch in Google Scholar
  • 15 Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005; 38: 1103-1111
    CrossrefPubMedSearch in Google Scholar
  • 16 Ellman GL, Courtney KD, Andres VJ et al. A new and rapid colorimetric determination of acetyl cholinesterase activity. Biochem Pharmacol 1961; 7: 88-95
    CrossrefPubMedSearch in Google Scholar
  • 17 Levine R, Garland D, Oliver C. Determination of carbonyl content of oxidatively modified proteins. Methods Enzymal 1990; 186: 464
    PubMedSearch in Google Scholar
  • 18 Reznick AZ, Packer L. Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol 1994; 233: 357
    PubMedSearch in Google Scholar
  • 19 Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95: 351-358
    CrossrefPubMedSearch in Google Scholar
  • 20 Tietez F. Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem 1969; 27: 502
    CrossrefPubMedSearch in Google Scholar
  • 21 Sun Y, Oberley LW, Ying L. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988; 34: 497-500
    CrossrefPubMedSearch in Google Scholar
  • 22 Habig WH, Pabst MJ, Jakoby WB. GlutathioneS-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 1974; 249: 7130-7139
    PubMedSearch in Google Scholar
  • 23 Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterisation of erythrocyte glutathione peroxidase. J Lab Clin Med 1967; 70: 158-169
    PubMedSearch in Google Scholar
  • 24 Aebi H. Catalase. In: Bergmeyer U. (ed.). Methods of enzymatic analysis. Academic Press; New York: 1974: 673-684
    CrossrefSearch in Google Scholar
  • 25 Bonting SL. Sodium-potassium activated adenosine triphosphatase and cation transport. In: Bittar EE. (ed.). Membranes and ion transport. London: Wiley-Interscience; 1970: 257-263
    Search in Google Scholar
  • 26 Ohnishi T, Suzuki T, Suzuki Y et al. Comparative study of plasma membrane Mg 2+ -ATPase activities in normal, regenerating and malignant cells. Biochim Biophy Acta 1982; 684: 67-74
    CrossrefPubMedSearch in Google Scholar
  • 27 Hjerten S, Pan H. Purification and characterization of two forms of a low-affinity Ca2+ -ATPase from erythrocyte membranes. Biochim Biophys Acta 1983; 728: 281-288
    CrossrefPubMedSearch in Google Scholar
  • 28 (ATSDR) . Guidance manual for the assessment of joint toxic actions of chemical mixtures. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service; 2004
    Search in Google Scholar
  • 29 Okuda B, Iwamoto Y, Tachibana H et al. Parkinsonism after acute cadmium poisoning. Clin Neurol Neurosurg 1997; 99: 263-265
    CrossrefPubMedSearch in Google Scholar
  • 30 Jiang LF, Yao TM, Zhu ZL et al. Impacts of Cd(II) on the conformation and self-aggregation of Alzheimer’s tau fragment corresponding to the third repeat of microtubule-binding domain. Biochimica et Biophysica Acta 2007; 1774: 1414-1421
    CrossrefPubMedSearch in Google Scholar
  • 31 Xu B, Chen S, Luo Y et al. Calcium signaling is involved in cadmium-induced neuronal apoptosis via induction of reactive oxygen species and activation of MAPK/mTOR network. PLoS One 2011; 6: e19052 2011
    CrossrefPubMedSearch in Google Scholar
  • 32 Yuan Y, Jiang C-y, Xu H et al. Cadmium-Induced Apoptosis in Primary Rat Cerebral Cortical Neurons Culture Is Mediated by a Calcium Signaling Pathway. PLoS ONE 2013; 8: e64330
    CrossrefPubMedSearch in Google Scholar
  • 33 Chen L, Liu L, Huang S. Cadmium activates the mitogen-activated protein kinase (MAPK) pathway via induction of reactive oxygen species and inhibition of protein phosphatases 2A and 5. Free Rad Biol and Med 2008; 45: 1035-1044
    CrossrefPubMedSearch in Google Scholar
  • 34 Sonee M, Sum T, Wang C et al. The soy isoflavone, genistein, protects human cortical neuronal cells from oxidative stress. Neurotoxicol 2004; 25: 885-891
    CrossrefPubMedSearch in Google Scholar
  • 35 Shagirtha K, Muthumani M, Prabu SM. Melatonin abrogates cadmium induced oxidative stress related neurotoxicity in rats. Eur Rev Med Pharmacol Sci 2011; 15: 1039-1050
    PubMedSearch in Google Scholar
  • 36 Arora A, Valcic S, Cornejo S et al. Reactions of genistein with alkylperoxyl radicals. Chem Res Toxicol 2000; 13: 638-645
    CrossrefPubMedSearch in Google Scholar
  • 37 Wei H, Wei L, Frenkel L et al. Inhibition of tumor promoter-induced hydrogen peroxide formation in vitro and in vivo by genistein. Nutr Cancer 1993; 20: 1-12
    CrossrefPubMedSearch in Google Scholar
  • 38 Chang HC, Churchewell MI, Delclos KB et al. Mass spectrometric determination of genistein tissue distribution in diet-exposed Sprage-Dawley rats. J Nutr 2000; 130: 1963-1970
    PubMedSearch in Google Scholar
  • 39 Pari L, Murugavel P. Diallyl tetrasulphide improves cadmium-induced alterations of acetylcholinesterase, ATPases and oxidative stress in brain of rats. Toxicology 2007; 234: 44-50
    CrossrefPubMedSearch in Google Scholar
  • 40 Fan Y, Wang C, Zhang Y et al. Genistein ameliorates adverse cardiac effects induced by arsenic trioxide through preventing cardiomyocytes apoptosis. Cell Physiol Biochem 2013; 31: 80-91
    CrossrefPubMedSearch in Google Scholar
  • 41 McDowell ML, Das A, Smith JA et al. Neuroprotective effects of genistein in VSC4.1 motoneurons exposed to activated microglial cytokines. Neurochem Int 2011; 59: 175-184
    CrossrefPubMedSearch in Google Scholar