Molecular Neurobiology

, Volume 52, Issue 3, pp 1504–1520 | Cite as

Lead Intoxication Synergies of the Ethanol-Induced Toxic Responses in Neuronal Cells—PC12

  • V. Kumar
  • V. K. Tripathi
  • S. Jahan
  • M. Agrawal
  • A. Pandey
  • V. K. Khanna
  • A. B. Pant


Lead (Pb)-induced neurodegeneration and its link with widespread neurobehavioral changes are well documented. Experimental evidences suggest that ethanol could enhance the absorption of metals in the body, and alcohol consumption may increase the susceptibility to metal intoxication in the brain. However, the underlying mechanism of ethanol action in affecting metal toxicity in brain cells is poorly understood. Thus, an attempt was made to investigate the modulatory effect of ethanol on Pb intoxication in PC12 cells, a rat pheochromocytoma. Cells were co-exposed to biological safe doses of Pb (10 μM) and ethanol (200 mM), and data were compared to the response of cells which received independent exposure to these chemicals at similar doses. Ethanol (200 mM) exposure significantly aggravated the Pb-induced alterations in the end points associated with oxidative stress and apoptosis. The finding confirms the involvement of reactive oxygen species (ROS)-mediated oxidative stress, and impairment of mitochondrial membrane potential, which subsequently facilitate the translocation of triggering proteins between cytoplasm and mitochondria. We further confirmed the apoptotic changes due to induction of mitochondria-mediated caspase cascade. These cellular changes were found to recover significantly, if the cells are exposed to N-acetyl cysteine (NAC), a known antioxidant. Our data suggest that ethanol may potentiate Pb-induced cellular damage in brain cells, but such damaging effects could be recovered by inhibition of ROS generation. These results open up further possibilities for the design of new therapeutics based on antioxidants to prevent neurodegeneration and associated health problems.


Neurotoxicity Pb Ethanol PC12 cells 



The authors are grateful to the Director, IITR, Lucknow, India, for his keen interest in the study. Financial support from Department of Biotechnology, Ministry of Science & Technology, Government of India, New Delhi, India [Grant No. 102/IFD/SAN/PR1524/2010–2011]; Department of Science and Technology, Ministry of Science & Technology, Government of India, New Delhi, India [Grant No. SR/SO/Z 36/2007/91/10]; and Council of Scientific & Industrial Research, Government of India, New Delhi, India [Grant No. BSC0111/INDEPTH/ CSIR Network Project] is acknowledged. Indian Council of Medical Research, (ICMR), New Delhi, India, is acknowledged for providing the fellowship to Dr. Vivek Kumar. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article.

Conflict of Interest

The authors declare no conflict of interest.


  1. 1.
    Briggs D (2003) Environmental pollution and the global burden of disease. Br Med Bull 68:1–24CrossRefPubMedGoogle Scholar
  2. 2.
    Tong S, von Schirnding YE, Prapamontol T (2000) Environmental lead exposure: a public health problem of global dimensions. Bull World Health Organ 78:1068–1077PubMedPubMedCentralGoogle Scholar
  3. 3.
    Florea AM, Busselberg D (2006) Occurrence, use and potential toxic effects of metals and metal compounds. Biometals 19:419–427CrossRefPubMedGoogle Scholar
  4. 4.
    Giordano G, Costa LG (2012) Developmental neurotoxicity: some old and new issues. ISRN Toxicol 2012:814795PubMedPubMedCentralGoogle Scholar
  5. 5.
    Zheng W, Aschner M, Ghersi-Egea JF (2003) Brain barrier systems: a new frontier in metal neurotoxicological research. Toxicol Appl Pharmacol 192:1–11CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Kolesarova A, Roychoudhury S, Slivkova J, Sirotkin A, Capcarova M, Massanyi P (2010) In vitro study on the effects of lead and mercury on porcine ovarian granulosa cells. J Environ Sci Health A Tox Hazard Subst Environ Eng 45:320–331CrossRefPubMedGoogle Scholar
  7. 7.
    Mrugesh T, Dipa L, Manishika G (2011) Effect of lead on human erythrocytes: an in vitro study. Acta Pol Pharm 68:653–656PubMedGoogle Scholar
  8. 8.
    Conterato GM, Augusti PR, Somacal S, Einsfeld L, Sobieski R, Torres JR, Emanuelli T (2007) Effect of lead acetate on cytosolic thioredoxin reductase activity and oxidative stress parameters in rat kidneys. Basic Clin Pharmacol Toxicol 101:96–100CrossRefPubMedGoogle Scholar
  9. 9.
    Dewanjee S, Sahu R, Karmakar S, Gangopadhyay M (2013) Toxic effects of lead exposure in Wistar rats: involvement of oxidative stress and the beneficial role of edible jute (Corchorus olitorius) leaves. Food Chem Toxicol 55:78–91CrossRefPubMedGoogle Scholar
  10. 10.
    Hu H, Shih R, Rothenberg S, Schwartz BS (2007) The epidemiology of lead toxicity in adults: measuring dose and consideration of other methodologic issues. Environ Health Perspect 115:455–462CrossRefPubMedGoogle Scholar
  11. 11.
    Lidsky TI, Schneider JS (2003) Lead neurotoxicity in children: basic mechanisms and clinical correlates. Brain 126:5–19CrossRefPubMedGoogle Scholar
  12. 12.
    Lu X, Jin C, Yang J, Liu Q, Wu S, Li D, Guan Y, Cai Y (2013) Prenatal and lactational lead exposure enhanced oxidative stress and altered apoptosis status in offspring rats’ hippocampus. Biol Trace Elem Res 151:75–84CrossRefPubMedGoogle Scholar
  13. 13.
    Sanders T, Liu Y, Buchner V, Tchounwou PB (2009) Neurotoxic effects and biomarkers of lead exposure: a review. Rev Environ Health 24:15–45CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Chen L, Yang X, Jiao H, Zhao B (2003) Tea catechins protect against lead-induced ROS formation, mitochondrial dysfunction, and calcium dysregulation in PC12 cells. Chem Res Toxicol 16:1155–1161CrossRefPubMedGoogle Scholar
  15. 15.
    Flora SJ, Saxena G, Mehta A (2007) Reversal of lead-induced neuronal apoptosis by chelation treatment in rats: role of reactive oxygen species and intracellular Ca(2+). J Pharmacol Exp Ther 322:108–116CrossRefPubMedGoogle Scholar
  16. 16.
    He L, Poblenz AT, Medrano CJ, Fox DA (2000) Lead and calcium produce rod photoreceptor cell apoptosis by opening the mitochondrial permeability transition pore. J Biol Chem 275:12175–12184CrossRefPubMedGoogle Scholar
  17. 17.
    Aimo L, Oteiza PI (2006) Zinc deficiency increases the susceptibility of human neuroblastoma cells to lead-induced activator protein-1 activation. Toxicol Sci 91:184–191CrossRefPubMedGoogle Scholar
  18. 18.
    Patra RC, Rautray AK, Swarup D (2011) Oxidative stress in lead and cadmium toxicity and its amelioration. Vet Med Int 2011:457327CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Hernandez M, Margalida A (2009) Assessing the risk of lead exposure for the conservation of the endangered Pyrenean bearded vulture (Gypaetus barbatus) population. Environ Res 109:837–842CrossRefPubMedGoogle Scholar
  20. 20.
    Brust JC (2010) Ethanol and cognition: indirect effects, neurotoxicity and neuroprotection: a review. Int J Environ Res Public Health 7:1540–1557CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Crews FT, Braun CJ, Hoplight B, Switzer RC 3rd, Knapp DJ (2000) Binge ethanol consumption causes differential brain damage in young adolescent rats compared with adult rats. Alcohol Clin Exp Res 24:1712–1723CrossRefPubMedGoogle Scholar
  22. 22.
    Haorah J, Knipe B, Leibhart J, Ghorpade A, Persidsky Y (2005) Alcohol-induced oxidative stress in brain endothelial cells causes blood–brain barrier dysfunction. J Leukoc Biol 78:1223–1232CrossRefPubMedGoogle Scholar
  23. 23.
    Singh AK, Jiang Y, Gupta S, Benlhabib E (2007) Effects of chronic ethanol drinking on the blood brain barrier and ensuing neuronal toxicity in alcohol-preferring rats subjected to intraperitoneal LPS injection. Alcohol Alcohol 42:385–399CrossRefPubMedGoogle Scholar
  24. 24.
    Costa LG, Guizzetti M, Burry M, Oberdoerster J (2002) Developmental neurotoxicity: do similar phenotypes indicate a common mode of action? A comparison of fetal alcohol syndrome, toluene embryopathy and maternal phenylketonuria. Toxicol Lett 127:197–205CrossRefPubMedGoogle Scholar
  25. 25.
    Goodlett CR, Horn KH, Zhou FC (2005) Alcohol teratogenesis: mechanisms of damage and strategies for intervention. Exp Biol Med (Maywood) 230:394–406CrossRefGoogle Scholar
  26. 26.
    Mulholland PJ, Self RL, Stepanyan TD, Little HJ, Littleton JM, Prendergast MA (2005) Thiamine deficiency in the pathogenesis of chronic ethanol-associated cerebellar damage in vitro. Neuroscience 135:1129–1139CrossRefPubMedGoogle Scholar
  27. 27.
    Kroener S, Mulholland PJ, New NN, Gass JT, Becker HC, Chandler LJ (2012) Chronic alcohol exposure alters behavioral and synaptic plasticity of the rodent prefrontal cortex. PLoS ONE 7:e37541CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Ridley NJ, Draper B, Withall A (2013) Alcohol-related dementia: an update of the evidence. Alzheimers Res Ther 5:3CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Tiwari V, Kuhad A, Chopra K (2009) Suppression of neuro-inflammatory signaling cascade by tocotrienol can prevent chronic alcohol-induced cognitive dysfunction in rats. Behav Brain Res 203:296–303CrossRefPubMedGoogle Scholar
  30. 30.
    de la Monte SM, Kril JJ (2014) Human alcohol-related neuropathology. Acta Neuropathol 127:71–90CrossRefPubMedGoogle Scholar
  31. 31.
    Flanagan DE, Pratt E, Murphy J, Vaile JC, Petley GW, Godsland IF, Kerr D (2002) Alcohol consumption alters insulin secretion and cardiac autonomic activity. Eur J Clin Invest 32:187–192CrossRefPubMedGoogle Scholar
  32. 32.
    Wang X, Ke Z, Chen G, Xu M, Bower KA, Frank JA, Zhang Z, Shi X, Luo J (2012) Cdc42-dependent activation of NADPH oxidase is involved in ethanol-induced neuronal oxidative stress. PLoS ONE 7:e38075CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Ramachandran V, Watts LT, Maffi SK, Chen J, Schenker S, Henderson G (2003) Ethanol-induced oxidative stress precedes mitochondrially mediated apoptotic death of cultured fetal cortical neurons. J Neurosci Res 74:577–588CrossRefPubMedGoogle Scholar
  34. 34.
    Kamens HM, Phillips TJ (2008) A role for neuronal nicotinic acetylcholine receptors in ethanol-induced stimulation, but not cocaine- or methamphetamine-induced stimulation. Psychopharmacology (Berl) 196:377–387CrossRefGoogle Scholar
  35. 35.
    Probst-Hensch N, Braun-Fahrlaender C, Bodenmann A, Ackermann-Liebrich U (1993) Alcohol consumption and other lifestyle factors: avoidable sources of excess lead exposure. Soz Praventivmed 38:43–50CrossRefPubMedGoogle Scholar
  36. 36.
    Telisman S, Cvitkovic P, Jurasovic J, Pizent A, Gavella M, Rocic B (2000) Semen quality and reproductive endocrine function in relation to biomarkers of lead, cadmium, zinc, and copper in men. Environ Health Perspect 108:45–53CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Flora SJ, Kumar D, Sachan SR, Das Gupta S (1991) Combined exposure to lead and ethanol on tissue concentration of essential metals and some biochemical indices in rat. Biol Trace Elem Res 28:157–164CrossRefPubMedGoogle Scholar
  38. 38.
    Flora SJ, Mittal M, Mehta A (2008) Heavy metal induced oxidative stress & its possible reversal by chelation therapy. Indian J Med Res 128:501–523PubMedGoogle Scholar
  39. 39.
    Gupta V, Gill KD (2000) Influence of ethanol on lead distribution and biochemical changes in rats exposed to lead. Alcohol 20:9–17CrossRefPubMedGoogle Scholar
  40. 40.
    Kupraszewicz E, Brzoska MM (2013) Excessive ethanol consumption under exposure to lead intensifies disorders in bone metabolism: a study in a rat model. Chem Biol Interact 203:486–501CrossRefPubMedGoogle Scholar
  41. 41.
    Agrawal M, Kumar V, Kashyap MP, Khanna VK, Randhawa GS, Pant AB (2011) Ischemic insult induced apoptotic changes in PC12 cells: protection by trans resveratrol. Eur J Pharmacol 666:5–11CrossRefPubMedGoogle Scholar
  42. 42.
    Agrawal M, Kumar V, Singh AK, Kashyap MP, Khanna VK, Siddiqui MA, Pant AB (2013) trans-Resveratrol protects ischemic PC12 Cells by inhibiting the hypoxia associated transcription factors and increasing the levels of antioxidant defense enzymes. ACS Chem Neurosci 4:285–294CrossRefPubMedGoogle Scholar
  43. 43.
    Akhtar MJ, Ahamed M, Kumar S, Siddiqui H, Patil G, Ashquin M, Ahmad I (2010) Nanotoxicity of pure silica mediated through oxidant generation rather than glutathione depletion in human lung epithelial cells. Toxicology 276:95–102CrossRefPubMedGoogle Scholar
  44. 44.
    Siddiqui MA, Kashyap MP, Kumar V, Al-Khedhairy AA, Musarrat J, Pant AB (2010) Protective potential of trans-resveratrol against 4-hydroxynonenal induced damage in PC12 cells. Toxicol In Vitro 24:1592–1598CrossRefPubMedGoogle Scholar
  45. 45.
    Ghosh S, Patel N, Rahn D, McAllister J, Sadeghi S, Horwitz G, Berry D, Wang KX, Swerdlow RH (2007) The thiazolidinedione pioglitazone alters mitochondrial function in human neuron-like cells. Mol Pharmacol 71:1695–1702CrossRefPubMedGoogle Scholar
  46. 46.
    Waterhouse NJ, Steel R, Kluck R, Trapani JA (2004) Assaying cytochrome C translocation during apoptosis. Methods Mol Biol 284:307–313PubMedGoogle Scholar
  47. 47.
    Cezard C, Demarquilly C, Boniface M, Haguenoer JM (1992) Influence of the degree of exposure to lead on relations between alcohol consumption and the biological indices of lead exposure: epidemiological study in a lead acid battery factory. Br J Ind Med 49:645–647PubMedPubMedCentralGoogle Scholar
  48. 48.
    Molina MF, Sanchez-Reus I, Iglesias I, Benedi J (2003) Quercetin, a flavonoid antioxidant, prevents and protects against ethanol-induced oxidative stress in mouse liver. Biol Pharm Bull 26:1398–1402CrossRefPubMedGoogle Scholar
  49. 49.
    Flora SJS, Gautam P, Kushwaha P (2012) Lead and ethanol co-exposure lead to blood oxidative stress and subsequent neuronal apoptosis in rats. Alcohol and alcoholism:agr152Google Scholar
  50. 50.
    Suntres ZE (2002) Role of antioxidants in paraquat toxicity. Toxicology 180:65–77CrossRefPubMedGoogle Scholar
  51. 51.
    Shavali S, Sens DA (2008) Synergistic neurotoxic effects of arsenic and dopamine in human dopaminergic neuroblastoma SH-SY5Y cells. Toxicol Sci 102:254–261CrossRefPubMedGoogle Scholar
  52. 52.
    Bolin CM, Basha R, Cox D, Zawia NH, Maloney B, Lahiri DK, Cardozo-Pelaez F (2006) Exposure to lead and the developmental origin of oxidative DNA damage in the aging brain. FASEB J 20:788–790PubMedGoogle Scholar
  53. 53.
    Fazakas Z, Lengyel Z, Nagymajtenyi L (2005) Combined effects of subchronic exposure to lead, mercury and alcohol on the spontaneous and evoked cortical activity in rats. Arhiv za higijenu rada i toksikologiju 56:249–256PubMedGoogle Scholar
  54. 54.
    Kashyap MP, Singh AK, Siddiqui MA, Kumar V, Tripathi VK, Khanna VK, Yadav S, Jain SK, Pant AB (2010) Caspase cascade regulated mitochondria mediated apoptosis in monocrotophos exposed PC12 cells. Chem Res Toxicol 23:1663–1672CrossRefPubMedGoogle Scholar
  55. 55.
    Galluzzi L, Morselli E, Kepp O, Tajeddine N, Kroemer G (2008) Targeting p53 to mitochondria for cancer therapy. Cell Cycle 7:1949–1955CrossRefPubMedGoogle Scholar
  56. 56.
    Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87:99–163CrossRefPubMedGoogle Scholar
  57. 57.
    Namazi MR (2009) Cytochrome-P450 enzymes and autoimmunity: expansion of the relationship and introduction of free radicals as the link. J Autoimmune Dis 6:4CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Poplawski T, Pawlowska E, Wisniewska-Jarosinska M, Ksiazek D, Wozniak K, Szczepanska J, Blasiak J (2009) Cytotoxicity and genotoxicity of glycidyl methacrylate. Chem Biol Interact 180:69–78CrossRefPubMedGoogle Scholar
  59. 59.
    Segui B, Legembre P (2010) Redistribution of CD95 into the lipid rafts to treat cancer cells? Recent Pat Anticancer Drug Discov 5:22–28CrossRefPubMedGoogle Scholar
  60. 60.
    Moll UM, Wolff S, Speidel D, Deppert W (2005) Transcription-independent pro-apoptotic functions of p53. Curr Opin Cell Biol 17:631–636CrossRefPubMedGoogle Scholar
  61. 61.
    Yu J, Zhang L (2005) The transcriptional targets of p53 in apoptosis control. Biochem Biophys Res Commun 331:851–858CrossRefPubMedGoogle Scholar
  62. 62.
    Bargonetti J, Manfredi JJ (2002) Multiple roles of the tumor suppressor p53. Curr Opin Oncol 14:86–91CrossRefPubMedGoogle Scholar
  63. 63.
    Cui Q, Yu JH, Wu JN, Tashiro S, Onodera S, Minami M, Ikejima T (2007) P53-mediated cell cycle arrest and apoptosis through a caspase-3- independent, but caspase-9-dependent pathway in oridonin-treated MCF-7 human breast cancer cells. Acta Pharmacol Sin 28:1057–1066CrossRefPubMedGoogle Scholar
  64. 64.
    Saleh AM, Vijayasarathy C, Masoud L, Kumar L, Shahin A, Kambal A (2003) Paraoxon induces apoptosis in EL4 cells via activation of mitochondrial pathways. Toxicol Appl Pharmacol 190:47–57CrossRefPubMedGoogle Scholar
  65. 65.
    Dejean LM, Martinez-Caballero S, Guo L, Hughes C, Teijido O, Ducret T, Ichas F, Korsmeyer SJ, Antonsson B, Jonas EA, Kinnally KW (2005) Oligomeric Bax is a component of the putative cytochrome c release channel MAC, mitochondrial apoptosis-induced channel. Mol Biol Cell 16:2424–2432CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Wang S, Yan-Neale Y, Cai R, Alimov I, Cohen D (2006) Activation of mitochondrial pathway is crucial for tumor selective induction of apoptosis by LAQ824. Cell Cycle 5:1662–1668CrossRefPubMedGoogle Scholar
  67. 67.
    Galluzzi L, Blomgren K, Kroemer G (2009) Mitochondrial membrane permeabilization in neuronal injury. Nat Rev Neurosci 10:481–494CrossRefPubMedGoogle Scholar
  68. 68.
    Zhao M, Zhang Y, Wang C, Fu Z, Liu W, Gan J (2009) Induction of macrophage apoptosis by an organochlorine insecticide acetofenate. Chem Res Toxicol 22:504–510CrossRefPubMedGoogle Scholar
  69. 69.
    Wang X, Zhu C, Hagberg H, Korhonen L, Sandberg M, Lindholm D, Blomgren K (2004) X-linked inhibitor of apoptosis (XIAP) protein protects against caspase activation and tissue loss after neonatal hypoxia-ischemia. Neurobiol Dis 16:179–189CrossRefPubMedGoogle Scholar
  70. 70.
    Petersen OH, Tepikin AV, Gerasimenko JV, Gerasimenko OV, Sutton R, Criddle DN (2009) Fatty acids, alcohol and fatty acid ethyl esters: toxic Ca2+ signal generation and pancreatitis. Cell Calcium 45:634–642CrossRefPubMedGoogle Scholar
  71. 71.
    Dostalek M, Hardy KD, Milne GL, Morrow JD, Chen C, Gonzalez FJ, Gu J, Ding X, Johnson DA, Johnson JA, Martin MV, Guengerich FP (2008) Development of oxidative stress by cytochrome P450 induction in rodents is selective for barbiturates and related to loss of pyridine nucleotide-dependent protective systems. J Biol Chem 283:17147–17157CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Lupp A, Kuhn UD, Karge E, Adam G, Fleck C (2006) In vitro investigations on the differential pro-oxidant and/or antioxidant properties of cyclosporin A and tacrolimus in human and rat liver microsomes. Int J Clin Pharmacol Ther 44:225–232CrossRefPubMedGoogle Scholar
  73. 73.
    Mari M, Cederbaum AI (2001) Induction of catalase, alpha, and microsomal glutathione S-transferase in CYP2E1 overexpressing HepG2 cells and protection against short-term oxidative stress. Hepatology 33:652–661CrossRefPubMedGoogle Scholar
  74. 74.
    Hewitt R, Forero A, Luncsford PJ, Martin FL (2007) Enhanced micronucleus formation and modulation of BCL-2:BAX in MCF-7 cells after exposure to binary mixtures. Environ Health Perspect 115(Suppl 1):129–136CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Cederbaum AI (2006) CYP2E1—biochemical and toxicological aspects and role in alcohol-induced liver injury. Mt Sinai J Med 73:657–672PubMedGoogle Scholar
  76. 76.
    Gong P, Cederbaum AI (2006) Nrf2 is increased by CYP2E1 in rodent liver and HepG2 cells and protects against oxidative stress caused by CYP2E1. Hepatology 43:144–153CrossRefPubMedGoogle Scholar
  77. 77.
    Bradford BU, Kono H, Isayama F, Kosyk O, Wheeler MD, Akiyama TE, Bleye L, Krausz KW, Gonzalez FJ, Koop DR, Rusyn I (2005) Cytochrome P450 CYP2E1, but not nicotinamide adenine dinucleotide phosphate oxidase, is required for ethanol-induced oxidative DNA damage in rodent liver. Hepatology 41:336–344CrossRefPubMedGoogle Scholar
  78. 78.
    Raza H, John A (2006) 4-Hydroxynonenal induces mitochondrial oxidative stress, apoptosis and expression of glutathione S-transferase A4-4 and cytochrome P450 2E1 in PC12 cells. Toxicol Appl Pharmacol 216:309–318CrossRefPubMedGoogle Scholar
  79. 79.
    Kashyap MP, Singh AK, Kumar V, Tripathi VK, Srivastava RK, Agrawal M, Khanna VK, Yadav S, Jain SK, Pant AB (2011) Monocrotophos induced apoptosis in PC12 cells: role of xenobiotic metabolizing cytochrome P450s. PLoS ONE 6:e17757CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Engle MR, Singh SP, Czernik PJ, Gaddy D, Montague DC, Ceci JD, Yang Y, Awasthi S, Awasthi YC, Zimniak P (2004) Physiological role of mGSTA4-4, a glutathione S-transferase metabolizing 4-hydroxynonenal: generation and analysis of mGsta4 null mouse. Toxicol Appl Pharmacol 194:296–308CrossRefPubMedGoogle Scholar
  81. 81.
    Wang L, Yang Y, Dwivedi S, Xu Y, Chu ET, Li J, Fitchett K, Boor PJ (2006) Manipulating glutathione-S-transferases may prevent the development of tolerance to nitroglycerin. Cardiovasc Toxicol 6:131–144CrossRefPubMedGoogle Scholar
  82. 82.
    Li CY, Lee JS, Ko YG, Kim JI, Seo JS (2000) Heat shock protein 70 inhibits apoptosis downstream of cytochrome c release and upstream of caspase-3 activation. J Biol Chem 275:25665–25671CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • V. Kumar
    • 1
    • 2
  • V. K. Tripathi
    • 1
    • 2
  • S. Jahan
    • 1
    • 2
  • M. Agrawal
    • 1
    • 2
  • A. Pandey
    • 1
    • 2
  • V. K. Khanna
    • 1
    • 2
  • A. B. Pant
    • 1
    • 2
  1. 1.In Vitro Toxicology LaboratoryIndian Institute of Toxicology ResearchLucknowIndia
  2. 2.Council of Scientific & Industrial ResearchNew DelhiIndia

Personalised recommendations