Arsenic-Induced Oxidative Stress: Evidence on In Vitro Models of Cardiovascular, Diabetes Mellitus Type 2 and Neurodegenerative Disorders

  • Rubén Ruíz-Ramos
  • Patricia Ostrosky-Wegman
  • Mariano E. CebriánEmail author
Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)


This chapter provides an overview of the evidence of oxidative stress and compensatory responses in response to arsenic exposure in diverse in vitro models of cardiovascular diseases, type 2 diabetes mellitus and neurodegenerative disorders. The studies described here are recent approaches related to (1) the presence of oxidative and nitrosative damage; (2) the activation of novel and sensitive oxidative stress targets providing an environment conducive to the onset and progression of these diseases. We emphasize the need for further studies exploring the usefulness of the novel oxidative and nitrosative stress targets as biological markers of As toxicity.


Arsenic Atherosclerosis CNS Endothelium dysfunction Hypertension ROS 



Alzheimer’s disease


AMP-activated kinase


Activator protein-1


Adipocyte-selective fatty acid-binding protein




CCAAT-enhancer binding protein α




Cardiovascular diseases


Dimethylarsinous acid




Dimethylarsinic acid


Extracellular signal regulated kinase


Glucose transporter 4




Human umbilical vein endothelial cells




c-Jun N-terminal kinase


Mitogen-activated protein kinases


Microtubule-associated protein-tau


Methylarsine oxide


Monocyte chemoattractant protein-1


Monomethylarsonous acid


Monomethylarsonic acid








Neurofilament high molecular weight subunit


Neurofibrillary tangles


Nuclear factor-κB


Nitric oxide


Nitric oxide synthases


NF-E2-related factor 2


3-Phosphoinositide-dependent kinase-1




Phosphatidylinositol 3-kinase




Protein kinase B


Peroxisome proliferative-activated receptor γ


Phosphatase and tensin homolog deleted on chromosome ten


Reactive nitrogen species


Reactive oxygen species


Type 1 sphingosine-1-phosphate


Stress-activated protein kinases


Diabetes mellitus type 2


Tyrosine aminotransferase


Tumor necrosis factor-α


Vascular endothelial cadherin


Vascular smooth muscle cells


  1. 1.
    Valko, M., et al., Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact, 2006. 160(1): p. 1–40.Google Scholar
  2. 2.
    Valko, M., et al., Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem, 2004. 266(1-2): p. 37–56.Google Scholar
  3. 3.
    Inoue, M., et al., Mitochondrial generation of reactive oxygen species and its role in aerobic life. Curr Med Chem, 2003. 10(23): p. 2495–505.Google Scholar
  4. 4.
    Gurr, J.R., et al., Nitric oxide production by arsenite. Mutat Res, 2003. 533(1-2): p. 173–82.Google Scholar
  5. 5.
    Liu, S.X., et al., Induction of oxyradicals by arsenic: implication for mechanism of genotoxicity. Proc Natl Acad Sci U S A, 2001. 98(4): p. 1643–8.Google Scholar
  6. 6.
    Alderton, W.K., C.E. Cooper, and R.G. Knowles, Nitric oxide synthases: structure, function and inhibition. Biochem J, 2001. 357(Pt 3): p. 593–615.Google Scholar
  7. 7.
    Bergendi, L., et al., Chemistry, physiology and pathology of free radicals. Life Sci, 1999. 65(18-19): p. 1865–74.Google Scholar
  8. 8.
    Kawashima, S. and M. Yokoyama, Dysfunction of endothelial nitric oxide synthase and atherosclerosis. Arterioscler Thromb Vasc Biol, 2004. 24(6): p. 998–1005.Google Scholar
  9. 9.
    Balakumar, P., T. Kaur, and M. Singh, Potential target sites to modulate vascular endothelial dysfunction: current perspectives and future directions. Toxicology, 2008. 245(1-2): p. 49–64.Google Scholar
  10. 10.
    Kitchin, K.T. and S. Ahmad, Oxidative stress as a possible mode of action for arsenic carcinogenesis. Toxicol Lett, 2003. 137(1-2): p. 3–13.Google Scholar
  11. 11.
    Halliwell, B. and M. Whiteman, Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? Br J Pharmacol, 2004. 142(2): p. 231–55.Google Scholar
  12. 12.
    Kligerman, A.D. and A.H. Tennant, Insights into the carcinogenic mode of action of arsenic. Toxicol Appl Pharmacol, 2007. 222(3): p. 281–8.Google Scholar
  13. 13.
    Diaz-Villasenor, A., et al., Arsenic-induced alteration in the expression of genes related to type 2 diabetes mellitus. Toxicol Appl Pharmacol, 2007. 225(2): p. 123–33.Google Scholar
  14. 14.
    Navas-Acien, A., et al., Arsenic exposure and cardiovascular disease: a systematic review of the epidemiologic evidence. Am J Epidemiol, 2005. 162(11): p. 1037–49.Google Scholar
  15. 15.
    Prozialeck, W.C., et al., The vascular system as a target of metal toxicity. Toxicol Sci, 2008. 102(2): p. 207–18.Google Scholar
  16. 16.
    Schmuck, E.M., et al., Characterization of the monomethylarsonate reductase and dehydroascorbate reductase activities of Omega class glutathione transferase variants: implications for arsenic metabolism and the age-at-onset of Alzheimer’s and Parkinson’s diseases. Pharmacogenet Genomics, 2005. 15(7): p. 493–501.Google Scholar
  17. 17.
    Vahidnia, A., G.B. van der Voet, and F.A. de Wolff, Arsenic neurotoxicity--a review. Hum Exp Toxicol, 2007. 26(10): p. 823–32.Google Scholar
  18. 18.
    Wang, C.H., et al., Biological gradient between long-term arsenic exposure and carotid atherosclerosis. Circulation, 2002. 105(15): p. 1804–9.Google Scholar
  19. 19.
    Hsueh, Y.M., et al., Low serum carotene level and increased risk of ischemic heart disease related to long-term arsenic exposure. Atherosclerosis, 1998. 141(2): p. 249–57.Google Scholar
  20. 20.
    Chiou, H.Y., et al., Dose-response relationship between prevalence of cerebrovascular disease and ingested inorganic arsenic. Stroke, 1997. 28(9): p. 1717–23.Google Scholar
  21. 21.
    Chen, C.J., et al., Increased prevalence of hypertension and long-term arsenic exposure. Hypertension, 1995. 25(1): p. 53–60.Google Scholar
  22. 22.
    Lee, M.Y. and K.K. Griendling, Redox signaling, vascular function, and hypertension. Antioxid Redox Signal, 2008. 10(6): p. 1045–59.Google Scholar
  23. 23.
    Lyle, A.N. and K.K. Griendling, Modulation of vascular smooth muscle signaling by reactive oxygen species. Physiology (Bethesda), 2006. 21: p. 269–80.Google Scholar
  24. 24.
    Garcia-Palmieri, M.R., The endothelium in health and in cardiovascular disease. P R Health Sci J, 1997. 16(2): p. 136–41.Google Scholar
  25. 25.
    Schalkwijk, C.G. and C.D. Stehouwer, Vascular complications in diabetes mellitus: the role of endothelial dysfunction. Clin Sci (Lond), 2005. 109(2): p. 143–59.Google Scholar
  26. 26.
    Chatterjee, A., S.M. Black, and J.D. Catravas, Endothelial nitric oxide (NO) and its pathophysiologic regulation. Vascul Pharmacol, 2008. 49(4-6): p. 134–40.Google Scholar
  27. 27.
    Davignon, J. and P. Ganz, Role of endothelial dysfunction in atherosclerosis. Circulation, 2004. 109(23 Suppl 1): p. III27–32.Google Scholar
  28. 28.
    Savoia, C. and E.L. Schiffrin, Vascular inflammation in hypertension and diabetes: molecular mechanisms and therapeutic interventions. Clin Sci (Lond), 2007. 112(7): p. 375–84.Google Scholar
  29. 29.
    Cai, H. and D.G. Harrison, Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res, 2000. 87(10): p. 840–4.Google Scholar
  30. 30.
    Libby, P., Multiple mechanisms of thrombosis complicating atherosclerotic plaques. Clin Cardiol, 2000. 23 Suppl 6: p. VI-3–7.Google Scholar
  31. 31.
    Simeonova, P.P. and M.I. Luster, Arsenic and atherosclerosis. Toxicol Appl Pharmacol, 2004. 198(3): p. 444–9.Google Scholar
  32. 32.
    Willerson, J.T. and P.M. Ridker, Inflammation as a cardiovascular risk factor. Circulation, 2004. 109(21 Suppl 1): p. II2–10.Google Scholar
  33. 33.
    Bunderson, M., J.D. Coffin, and H.D. Beall, Arsenic induces peroxynitrite generation and cyclooxygenase-2 protein expression in aortic endothelial cells: possible role in atherosclerosis. Toxicol Appl Pharmacol, 2002. 184(1): p. 11–8.Google Scholar
  34. 34.
    Tsou, T.C., et al., Arsenite enhances tumor necrosis factor-alpha-induced expression of vascular cell adhesion molecule-1. Toxicol Appl Pharmacol, 2005. 209(1): p. 10–8.Google Scholar
  35. 35.
    Jindal, S., M. Singh, and P. Balakumar, Effect of bis (maltolato) oxovanadium (BMOV) in uric acid and sodium arsenite-induced vascular endothelial dysfunction in rats. Int J Cardiol, 2008. 128(3): p. 383–91.Google Scholar
  36. 36.
    Nuntharatanapong, N., et al., EGF receptor-dependent JNK activation is involved in arsenite-induced p21Cip1/Waf1 upregulation and endothelial apoptosis. Am J Physiol Heart Circ Physiol, 2005. 289(1): p. H99–H107.Google Scholar
  37. 37.
    Balakumar, P. and J. Kaur, Arsenic exposure and cardiovascular disorders: an overview. Cardiovasc Toxicol, 2009. 9(4): p. 169–76.Google Scholar
  38. 38.
    Mertens, A. and P. Holvoet, Oxidized LDL and HDL: antagonists in atherothrombosis. FASEB J, 2001. 15(12): p. 2073–84.Google Scholar
  39. 39.
    Wang, C.H., et al., A review of the epidemiologic literature on the role of environmental arsenic exposure and cardiovascular diseases. Toxicol Appl Pharmacol, 2007. 222(3): p. 315–26.Google Scholar
  40. 40.
    Tseng, C.H., Cardiovascular disease in arsenic-exposed subjects living in the arseniasis-hyperendemic areas in Taiwan. Atherosclerosis, 2008. 199(1): p. 12–8.Google Scholar
  41. 41.
    Simeonova, P.P., et al., Arsenic exposure accelerates atherogenesis in apolipoprotein E(-/-) mice. Environ Health Perspect, 2003. 111(14): p. 1744–8.Google Scholar
  42. 42.
    Bunderson, M., et al., Arsenic exposure exacerbates atherosclerotic plaque formation and increases nitrotyrosine and leukotriene biosynthesis. Toxicol Appl Pharmacol, 2004. 201(1): p. 32–9.Google Scholar
  43. 43.
    Barchowsky, A., et al., Stimulation of reactive oxygen, but not reactive nitrogen species, in vascular endothelial cells exposed to low levels of arsenite. Free Radic Biol Med, 1999. 27(11-12): p. 1405–12.Google Scholar
  44. 44.
    Lynn, S., et al., NADH oxidase activation is involved in arsenite-induced oxidative DNA damage in human vascular smooth muscle cells. Circ Res, 2000. 86(5): p. 514–9.Google Scholar
  45. 45.
    Smith, K.R., L.R. Klei, and A. Barchowsky, Arsenite stimulates plasma membrane NADPH oxidase in vascular endothelial cells. Am J Physiol Lung Cell Mol Physiol, 2001. 280(3): p. L442–9.Google Scholar
  46. 46.
    Straub, A.C., et al., Arsenic requires sphingosine-1-phosphate type 1 receptors to induce angiogenic genes and endothelial cell remodeling. Am J Pathol, 2009. 174(5): p. 1949–58.Google Scholar
  47. 47.
    Schieffer, B., et al., Impact of interleukin-6 on plaque development and morphology in experimental atherosclerosis. Circulation, 2004. 110(22): p. 3493–500.Google Scholar
  48. 48.
    Griendling, K.K., et al., Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology. Arterioscler Thromb Vasc Biol, 2000. 20(10): p. 2175–83.Google Scholar
  49. 49.
    Irani, K., Oxidant signaling in vascular cell growth, death, and survival : a review of the roles of reactive oxygen species in smooth muscle and endothelial cell mitogenic and apoptotic signaling. Circ Res, 2000. 87(3): p. 179–83.Google Scholar
  50. 50.
    Wu, M.M., et al., Gene expression of inflammatory molecules in circulating lymphocytes from arsenic-exposed human subjects. Environ Health Perspect, 2003. 111(11): p. 1429–38.Google Scholar
  51. 51.
    Lee, P.C., I.C. Ho, and T.C. Lee, Oxidative stress mediates sodium arsenite-induced expression of heme oxygenase-1, monocyte chemoattractant protein-1, and interleukin-6 in vascular smooth muscle cells. Toxicol Sci, 2005. 85(1): p. 541–50.Google Scholar
  52. 52.
    Pereira, F.E., J.D. Coffin, and H.D. Beall, Activation of protein kinase C and disruption of endothelial monolayer integrity by sodium arsenite--Potential mechanism in the development of atherosclerosis. Toxicol Appl Pharmacol, 2007. 220(2): p. 164–77.Google Scholar
  53. 53.
    Fujiwara, Y., et al., Arsenite but not arsenate inhibits general proteoglycan synthesis in ­cultured arterial smooth muscle cells. J Toxicol Sci, 2008. 33(4): p. 487–92.Google Scholar
  54. 54.
    Klei, L.R. and A. Barchowsky, Positive signaling interactions between arsenic and ethanol for angiogenic gene induction in human microvascular endothelial cells. Toxicol Sci, 2008. 102(2): p. 319–27.Google Scholar
  55. 55.
    Bae, O.N., et al., Arsenite-enhanced procoagulant activity through phosphatidylserine exposure in platelets. Chem Res Toxicol, 2007. 20(12): p. 1760–8.Google Scholar
  56. 56.
    Bae, O.N., et al., Trivalent methylated arsenical-induced phosphatidylserine exposure and apoptosis in platelets may lead to increased thrombus formation. Toxicol Appl Pharmacol, 2009. 239(2): p. 144–53.Google Scholar
  57. 57.
    Sanders, K.M., Invited review: mechanisms of calcium handling in smooth muscles. J Appl Physiol, 2001. 91(3): p. 1438–49.Google Scholar
  58. 58.
    Lee, M.Y., et al., Inorganic arsenite potentiates vasoconstriction through calcium sensitization in vascular smooth muscle. Environ Health Perspect, 2005. 113(10): p. 1330–5.Google Scholar
  59. 59.
    Bilszta, J.L., G.J. Dusting, and F. Jiang, Arsenite increases vasoconstrictor reactivity in rat blood vessels: role of endothelial nitric oxide function. Int J Toxicol, 2006. 25(4): p. 303–10.Google Scholar
  60. 60.
    Bae, O.N., et al., Vascular smooth muscle dysfunction induced by monomethylarsonous acid (MMA III): a contributing factor to arsenic-associated cardiovascular diseases. Environ Res, 2008. 108(3): p. 300–8.Google Scholar
  61. 61.
    Pysher, M.D., Q.M. Chen, and R.R. Vaillancourt, Arsenic alters vascular smooth muscle cell focal adhesion complexes leading to activation of FAK-src mediated pathways. Toxicol Appl Pharmacol, 2008. 231(2): p. 135–41.Google Scholar
  62. 62.
    Wild, S., et al., Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care, 2004. 27(5): p. 1047–53.Google Scholar
  63. 63.
    Longnecker, M.P. and J.L. Daniels, Environmental contaminants as etiologic factors for diabetes. Environ Health Perspect, 2001. 109 Suppl 6: p. 871–6.Google Scholar
  64. 64.
    Navas-Acien, A., et al., Arsenic exposure and type 2 diabetes: a systematic review of the experimental and epidemiological evidence. Environ Health Perspect, 2006. 114(5): p. 641–8.Google Scholar
  65. 65.
    Nabi, A.H., M.M. Rahman, and L.N. Islam, Evaluation of biochemical changes in chronic arsenic poisoning among Bangladeshi patients. Int J Environ Res Public Health, 2005. 2(3-4): p. 385–93.Google Scholar
  66. 66.
    Chiu, H.F., et al., Does arsenic exposure increase the risk for diabetes mellitus? J Occup Environ Med, 2006. 48(1): p. 63–7.Google Scholar
  67. 67.
    Coronado-Gonzalez, J.A., et al., Inorganic arsenic exposure and type 2 diabetes mellitus in Mexico. Environ Res, 2007. 104(3): p. 383–9.Google Scholar
  68. 68.
    Meliker, J.R., et al., Arsenic in drinking water and cerebrovascular disease, diabetes mellitus, and kidney disease in Michigan: a standardized mortality ratio analysis. Environ Health, 2007. 6: p. 4.Google Scholar
  69. 69.
    Navas-Acien, A., et al., Arsenic exposure and prevalence of type 2 diabetes in US adults. JAMA, 2008. 300(7): p. 814–22.Google Scholar
  70. 70.
    Tseng, C.H., The potential biological mechanisms of arsenic-induced diabetes mellitus. Toxicol Appl Pharmacol, 2004. 197(2): p. 67–83.Google Scholar
  71. 71.
    Fridlyand, L.E. and L.H. Philipson, Does the glucose-dependent insulin secretion mechanism itself cause oxidative stress in pancreatic beta-cells? Diabetes, 2004. 53(8): p. 1942–8.Google Scholar
  72. 72.
    Maiese, K., Z.Z. Chong, and Y.C. Shang, Mechanistic insights into diabetes mellitus and oxidative stress. Curr Med Chem, 2007. 14(16): p. 1729–38.Google Scholar
  73. 73.
    Pi, J., et al., Reactive oxygen species as a signal in glucose-stimulated insulin secretion. Diabetes, 2007. 56(7): p. 1783–91.Google Scholar
  74. 74.
    Pi, J., et al., Persistent oxidative stress due to absence of uncoupling protein 2 associated with impaired pancreatic beta-cell function. Endocrinology, 2009. 150(7): p. 3040–8.Google Scholar
  75. 75.
    Houstis, N., E.D. Rosen, and E.S. Lander, Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature, 2006. 440(7086): p. 944–8.Google Scholar
  76. 76.
    Tiedge, M., et al., Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. Diabetes, 1997. 46(11): p. 1733–42.Google Scholar
  77. 77.
    Matsumura, N., et al., Study on free radicals and pancreatic fibrosis--pancreatic fibrosis induced by repeated injections of superoxide dismutase inhibitor. Pancreas, 2001. 22(1): p. 53–7.Google Scholar
  78. 78.
    Macfarlane, W.M., et al., Glucose stimulates translocation of the homeodomain transcription factor PDX1 from the cytoplasm to the nucleus in pancreatic beta-cells. J Biol Chem, 1999. 274(2): p. 1011–6.Google Scholar
  79. 79.
    Wauson, E.M., A.S. Langan, and R.L. Vorce, Sodium arsenite inhibits and reverses expression of adipogenic and fat cell-specific genes during in vitro adipogenesis. Toxicol Sci, 2002. 65(2): p. 211–9.Google Scholar
  80. 80.
    Bazuine, M., et al., Arsenite stimulated glucose transport in 3T3-L1 adipocytes involves both Glut4 translocation and p38 MAPK activity. Eur J Biochem, 2003. 270(19): p. 3891–903.Google Scholar
  81. 81.
    Pi, J., et al., Transcription factor Nrf2 activation by inorganic arsenic in cultured keratinocytes: involvement of hydrogen peroxide. Exp Cell Res, 2003. 290(2): p. 234–45.Google Scholar
  82. 82.
    Bodwell, J.E., L.A. Kingsley, and J.W. Hamilton, Arsenic at very low concentrations alters glucocorticoid receptor (GR)-mediated gene activation but not GR-mediated gene repression: complex dose-response effects are closely correlated with levels of activated GR and require a functional GR DNA binding domain. Chem Res Toxicol, 2004. 17(8): p. 1064–76.Google Scholar
  83. 83.
    Hamilton, J.W., et al., Molecular basis for effects of carcinogenic heavy metals on inducible gene expression. Environ Health Perspect, 1998. 106 Suppl 4: p. 1005–15.Google Scholar
  84. 84.
    Walton, F.S., et al., Inhibition of insulin-dependent glucose uptake by trivalent arsenicals: possible mechanism of arsenic-induced diabetes. Toxicol Appl Pharmacol, 2004. 198(3): p. 424–33.Google Scholar
  85. 85.
    Paul, D.S., et al., Molecular mechanisms of the diabetogenic effects of arsenic: inhibition of insulin signaling by arsenite and methylarsonous acid. Environ Health Perspect, 2007. 115(5): p. 734–42.Google Scholar
  86. 86.
    Paul, D.S., et al., Examination of the effects of arsenic on glucose homeostasis in cell culture and animal studies: development of a mouse model for arsenic-induced diabetes. Toxicol Appl Pharmacol, 2007. 222(3): p. 305–14.Google Scholar
  87. 87.
    Izquierdo-Vega, J.A., et al., Diabetogenic effects and pancreatic oxidative damage in rats subchronically exposed to arsenite. Toxicol Lett, 2006. 160(2): p. 135–42.Google Scholar
  88. 88.
    Diaz-Villasenor, A., et al., Sodium arsenite impairs insulin secretion and transcription in pancreatic beta-cells. Toxicol Appl Pharmacol, 2006. 214(1): p. 30–4.Google Scholar
  89. 89.
    Fu, J., et al., Low Level Arsenic Impairs Glucose-Stimulated Insulin Secretion in Pancreatic Beta-Cells: Involvement of Cellular Adaptive Response to Oxidative Stress. Environ Health Perspect, 2010.Google Scholar
  90. 90.
    Grandjean, P. and P.J. Landrigan, Developmental neurotoxicity of industrial chemicals. Lancet, 2006. 368(9553): p. 2167–78.Google Scholar
  91. 91.
    Rosado, J.L., et al., Arsenic exposure and cognitive performance in Mexican schoolchildren. Environ Health Perspect, 2007. 115(9): p. 1371–5.Google Scholar
  92. 92.
    Trojanowski, J.Q. and V.M. Lee, “Fatal attractions” of proteins. A comprehensive hypothetical mechanism underlying Alzheimer’s disease and other neurodegenerative disorders. Ann N Y Acad Sci, 2000. 924: p. 62–7.Google Scholar
  93. 93.
    Giasson, B.I., et al., The environmental toxin arsenite induces tau hyperphosphorylation. Biochemistry, 2002. 41(51): p. 15376–87.Google Scholar
  94. 94.
    Su, B., et al., Oxidative stress signaling in Alzheimer’s disease. Curr Alzheimer Res, 2008. 5(6): p. 525–32.Google Scholar
  95. 95.
    Liu, Y., et al., Differential activation of ERK, JNK/SAPK and P38/CSBP/RK map kinase family members during the cellular response to arsenite. Free Radic Biol Med, 1996. 21(6): p. 771–81.Google Scholar
  96. 96.
    Zarazua, S., et al., Decreased nitric oxide production in the rat brain after chronic arsenic exposure. Neurochem Res, 2006. 31(8): p. 1069–77.Google Scholar
  97. 97.
    Das, J., et al., Arsenic-induced oxidative cerebral disorders: protection by taurine. Drug Chem Toxicol, 2009. 32(2): p. 93–102.Google Scholar
  98. 98.
    Namgung, U. and Z. Xia, Arsenite-induced apoptosis in cortical neurons is mediated by c-Jun N-terminal protein kinase 3 and p38 mitogen-activated protein kinase. J Neurosci, 2000. 20(17): p. 6442–51.Google Scholar
  99. 99.
    Namgung, U. and Z. Xia, Arsenic induces apoptosis in rat cerebellar neurons via activation of JNK3 and p38 MAP kinases. Toxicol Appl Pharmacol, 2001. 174(2): p. 130–8.Google Scholar
  100. 100.
    Dhar, P., N. Mohari, and R.D. Mehra, Preliminary morphological and morphometric study of rat cerebellum following sodium arsenite exposure during rapid brain growth (RBG) period. Toxicology, 2007. 234(1-2): p. 10–20.Google Scholar
  101. 101.
    Giasson, B.I. and W.E. Mushynski, Aberrant stress-induced phosphorylation of perikaryal neurofilaments. J Biol Chem, 1996. 271(48): p. 30404–9.Google Scholar
  102. 102.
    Vahidnia, A., et al., Arsenic metabolites affect expression of the neurofilament and tau genes: an in-vitro study into the mechanism of arsenic neurotoxicity. Toxicol In Vitro, 2007. 21(6): p. 1104–12.Google Scholar
  103. 103.
    Vahidnia, A., et al., Mechanism of arsenic-induced neurotoxicity may be explained through cleavage of p35 to p25 by calpain. Toxicol In Vitro, 2008. 22(3): p. 682–7.Google Scholar
  104. 104.
    Rios, R., et al., Decreased nitric oxide markers and morphological changes in the brain of arsenic-exposed rats. Toxicology, 2009. 261(1-2): p. 68–75.Google Scholar
  105. 105.
    Wang, X., et al., Arsenic Inhibits Neurite Outgrowth by Inhibiting LKB1-AMPK Signaling Pathway. Environ Health Perspect, 2010. doi: 10.1289/ehp.0901510Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Rubén Ruíz-Ramos
  • Patricia Ostrosky-Wegman
  • Mariano E. Cebrián
    • 1
    Email author
  1. 1.Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV-IPN)Ave. Instituto Politécnico NacionalMéxicoMexico

Personalised recommendations