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Protective Role of Quercetin on PCBs-Induced Oxidative Stress and Apoptosis in Hippocampus of Adult Rats

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Abstract

Polychlorinated biphenyls (PCBs) exposure produces neurodegeneration and induces oxidative stress. Neuroprotective role of quercetin, on PCBs induced apoptosis in hippocampus has not yet been studied. The present study is focused to see whether quercetin supplementation precludes against PCBs induced oxidative stress and hippocampal apoptosis. The results have shown that quercetin at 50 mg/kg bwt/30 days has protected oxidative stress in hippocampus of adult male rats. Quercetin, a free radical scavenger decreased the levels of oxidative stress markers in the hippocampus of simultaneous PCB+quercetin treated rats. The pro-apoptotic and anti-apoptotic molecules such as Bad, Bid, Bax and Bcl2 were altered in the hippocampus of experimental animals. PCBs increased the DNA damage and induced neurodegeneration were assessed by histological studies. PCB induced ROS may be linked to increased hippocampal neuronal apoptosis. Quercetin supplementation decreased the neuronal damage and scavenged the free radicals induced by PCBs and protects PCBs induced apoptosis and oxidative stress.

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References

  1. Hornbuckle KC, Carlson DL, Swackhamer DL et al (2006) Polychlorinated biphenyls in the Great Lakes. In: Hites RA (ed) The handbook of environmental chemistry: persistent organic pollutants in the Great Lakes. Springer, Berlin, pp 13–70

    Chapter  Google Scholar 

  2. Park JS, Linderholm L, Charles MJ et al (2007) Polychlorinated biphenyls and their hydroxylated metabolites (OH-PCBS) in pregnant women from eastern Slovakia. Environ Health Perspect 115:20–27

    Article  PubMed  CAS  Google Scholar 

  3. Korrick SA, Sagiv SK (2008) Polychlorinated biphenyls, organochlorine pesticides and neurodevelopment. Curr Opin Pediatr 20:198–204

    Article  PubMed  Google Scholar 

  4. Mariussen E, Fonnum F (2006) Neurochemical targets and behavioral effects of organohalogen compounds: an update. Crit Rev Toxicol 36:253–289

    Article  PubMed  CAS  Google Scholar 

  5. Pessah IN, Cherednichenko G, Lein PJ (2010) Minding the calcium store: Ryanodine receptor activation as a convergent mechanism of PCB toxicity. Pharmacol Ther 125:260–285

    Article  PubMed  CAS  Google Scholar 

  6. Martin LJ (2011) Neuronal cell death in nervous system development, disease, and injury (review). Int J Mol Med 7:455–478

    Google Scholar 

  7. White LD, Barone S Jr (2011) Qualitative and quantitative estimates of apoptosis from birth to senescence in the rat brain. Cell Death Differ 8:345–356

    Article  Google Scholar 

  8. Haddad JJ (2004) Redox and oxidant-mediated regulation of apoptosis signaling pathways: immuno-pharmaco-redox conception of oxidative siege versus cell death commitment. Int Immunopharmacol 4:475–493

    Article  PubMed  CAS  Google Scholar 

  9. Sanchez-Alonso JA, Lopez-Aparicio P, Recio MN et al (2004) Polychlorinated biphenyl mixtures (Aroclors) induce apoptosis via Bcl-2, Bax and caspase-3 proteins in neuronal cell cultures. Toxicol Lett 153:311–326

    Article  PubMed  CAS  Google Scholar 

  10. Dreiem A, Rykken S, Lehmler HJ et al (2009) Hydroxylated polychlorinated biphenyls increase reactive oxygen species formation and induce cell death in cultured cerebellar granule cells. Toxicol Appl Pharmacol 240:306–313

    Article  PubMed  CAS  Google Scholar 

  11. Mariussen E, Myhre O, Reistad T et al (2002) The polychlorinated biphenyl mixture aroclor 1254 induces death of rat cerebellar granule cells: the involvement of the N-methyl-D-aspartate receptor and reactive oxygen species. Toxicol Appl Pharmacol 179:137–144

    Article  PubMed  CAS  Google Scholar 

  12. Cory S, Adams JM (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nature Rev Can 2:647–656

    Article  CAS  Google Scholar 

  13. Howard AS, Fitzpatrick R, Pessah I et al (2003) Polychlorinated biphenyls induce caspase-dependent cell death in cultured embryonic rat hippocampal but not cortical neurons via activation of the ryanodine receptor. Toxicol Appl Pharmacol 190:72–86

    Article  PubMed  CAS  Google Scholar 

  14. Antonsson B, Conti F, Ciavatta A et al (1997) Inhibition of Bax channel-forming activity by Bcl-2. Science 277:370–372

    Article  PubMed  CAS  Google Scholar 

  15. Locksley RM, Killeen N, Lenardo MJ (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104:487–501

    Article  PubMed  CAS  Google Scholar 

  16. Hengertner MO (2000) The biochemistry of apoptosis. Nature 407:770–776

    Article  Google Scholar 

  17. Pawlikowska-Pawlega B, Guszecki WI, Misiak LE et al (2003) The study of the quercetin action on human erythrocyte membranes. Biochem Pharmacol 66:605–612

    Article  PubMed  CAS  Google Scholar 

  18. Ross JA, Kasum CM (2002) Dietary flavonoids: bioavailability, metabolic effects and safety. Ann Rev Nut 22:19–34

    Article  CAS  Google Scholar 

  19. Pu F, Mishima K, Irie K et al (2007) Neuroprotective effects of quercetin and rutin on spatial memory impairment in an 8-arm radial maze task and neuronal death induced by repeated cerebral ischemia in rats. J Pharmacol Sci 104:329–334

    Article  PubMed  CAS  Google Scholar 

  20. Huk I, Brovkovich V, Nanobash VJ et al (1998) Bioflavonoid quercetin scavenges superoxide and increases nitric oxide concentration in ischaemia-reperfusion injury: an experimental study. British J Sur 85:1080–1085

    Article  CAS  Google Scholar 

  21. Erden Inal M, Kahraman A (2000) The protective effect of flavonol quercetin against ultraviolet A induced oxidative stress in rats. Toxicology 154:21–29

    Article  PubMed  CAS  Google Scholar 

  22. Duarte J, Galisteo M, Ocete MA et al (2001) Effect of chronic quercetin treatment on hepatic oxidative status in spontaneously hypertensive rats. Mol Cell Biochem 221:155–160

    Article  PubMed  CAS  Google Scholar 

  23. Peres W, Tuñón MJ, Mato S et al (2000) Hepatoprotective effects of the flavonoid quercetin in rats with biliary obstruction. J Hepatol 33:742–750

    Article  PubMed  CAS  Google Scholar 

  24. Wadsworth TL, Koop DR (2001) Effects of Gingko biloba extract (Egb 761) and quercetin on lipopolysaccharide-induced release of nitric oxide. Chemico-Biol Interact 137:43–58

    Article  CAS  Google Scholar 

  25. Yang K, Lamprecht SA, Liu Y et al (2000) Chemoprevention studies of the flavonoids quercetin and rutin in normal and azoxymethane-treated mouse colon. Carcinogenesis 21:1655–1660

    Article  PubMed  CAS  Google Scholar 

  26. Vijayababu MR, Kanagaraj P, Arunkumar A et al (2006) Quercetin induces p53-independent apoptosis in human prostate cancer cells by modulating Bcl-2-related proteins: a possible mediation by IGFBP-3. Oncol Res 16:67–74

    PubMed  CAS  Google Scholar 

  27. Senthilkumar K, Elumalai P et al (2010) Quercetin regulates insulin like growth factor signaling and induces intrinsic and extrinsic pathway mediated apoptosis in androgen independent prostate cancer cells (PC-3). Mol Cell Biochem 1–2:173–184

    Article  Google Scholar 

  28. Senthilkumar K, Arunkumar R, Elumalai P et al (2011) Quercetin inhibits invasion, migration and signalling molecules involved in cell survival and proliferation of prostate cancer cell line (PC-3). Cell Biochem Func 2:87–95

    Article  Google Scholar 

  29. Sun SW, Yu HQ, Zhang H et al (2007) Quercetin attenuates spontaneous behavior and special memory impairment in D-galactose treated mice by increasing brain antioxidant capacity. Nut Res 27:169–175

    Article  CAS  Google Scholar 

  30. Venkataraman P, Selvakumar K, Krishnamoorthy G et al (2010) Effect of melatonin on PCB (Aroclor 1254) induced neuronal damage and changes in Cu/Zn superoxide dismutase and glutathione peroxidase-4 mRNA expression in cerebral cortex, cerebellum and hippocampus of adult rats. Neurosci Res 66:189–197

    Article  PubMed  CAS  Google Scholar 

  31. Pick E, Keisari Y (1981) Superoxide anion and H2O2 production by chemically elicited peritoneal macrophages-induction by multiple nonphagocytic stimuli. Cell Immunol 59:301–318

    Article  PubMed  CAS  Google Scholar 

  32. Devasagayam TP, Tarachand U (1987) Decreased lipid peroxidation in rat kidneys during gestation. Biochem Biophy Res Comm 145:134–138

    Article  CAS  Google Scholar 

  33. Levine RL, Williams JA, Stadtman ER et al (1994) Carbonyl assays for determination of oxidatively modified proteins. Met Enzymol 233:346–357

    Article  CAS  Google Scholar 

  34. Chomczynski P, Sacchi N (1987) Single step method of RNA isolation by acid guanidinium thiocyanatephenol-chloroform extraction. Anal Biochem 162:156–159

    Article  PubMed  CAS  Google Scholar 

  35. Lowry OH, Risebrough NJ, Farr AL et al (1951) Protein measurement with Folin phenol reagent. J Cell Biol 193:265–270

    CAS  Google Scholar 

  36. Mariussen E, Myhre O, Reistad T et al (2002) The polychlorinated biphenyl mixture aroclor 1254 induces death of rat cerebellar granule cells: the involvement of the N-methyl-D-aspartate receptor and reactive oxygen species. Toxicol App Pharmacol 179:137–144

    Article  CAS  Google Scholar 

  37. Schlezinger JJ, White RD, Slegemann JJ (1999) Oxidative inactivation of cytochrome P450 1A (CYP1A) stimulated by 3, 3′, 4, 4′–tetrachlorobiphenyl: production of reactive oxygen by vertebrate CYP1As. Mol Pharmacol 56:588–597

    PubMed  CAS  Google Scholar 

  38. McLean MR, Twaroski TP, Robertson LW (2000) Redox cycling of 2-(x’mono,-di,-trichlorophenyl)-1, 4benzoquinones, oxidation products of polychlorinated biphenyls. Arch Biochem Biophy 376:449–455

    Article  CAS  Google Scholar 

  39. Hochstein P, Ernster L (1963) ADP-activated lipid peroxidation coupled to the TPNH oxidase system of microsomes. Biochem Biophy Res Comm 12:388–394

    Article  CAS  Google Scholar 

  40. Kasai H, Crain PF, Kuchino Y et al (1986) Formation of 8-hydroxy- guanine moiety in cellular DNA by agents producing oxygen radical and evidence for its repair. Carcinogenesis 7:1849–1851

    Article  PubMed  CAS  Google Scholar 

  41. Griffith HR, Unswoth J, Blake DR et al (1988) Oxidation of amino acids within serum proteins. In: Rice-Evans (ed) Free radicals: chemistry. Pathology and Medicine Richeliue, London, pp 439–454

    Google Scholar 

  42. Sridhar M, Venkataraman P, Dhanammal S et al (2004) Impact of polychlorinated biphenyl (Aroclor 1254) and vitamin C on antioxidant system of rat ventral prostate. Asian J Androl 1:19–22

    Google Scholar 

  43. Krishnamoorthy G, Murugesan P, Muthuvel R et al (2005) Effect of Aroclor 1254 on Sertoli cellular antioxidant system, androgen binding protein and lactate in adult rat in vitro. Toxicology 212:195–205

    Article  PubMed  CAS  Google Scholar 

  44. Murugesan P, Kanagaraj P, Yuvaraj S et al (2005) The inhibitory effects of polychlorinated biphenyl Aroclor 1254 on Leydig cell LH receptors, steroidogenic enzymes and antioxidant enzymes in adult rats. Rep Toxicol 20:117–126

    Article  CAS  Google Scholar 

  45. Venkataraman P, Muthuvel R, Krishnamoorthy G et al (2007) PCB (Aroclor 1254) enhances oxidative damage in rat brain regions: protective role of ascorbic acid. Neurotoxicology 28:490–498

    Article  PubMed  CAS  Google Scholar 

  46. Reznick AZ, Packer L (1994) Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Met Enzymol 233:357–363

    Article  CAS  Google Scholar 

  47. Johnson MK, Loo G (2000) Effects of epigallocatechin gallate and quercetin on oxidative damage to cellular DNA. Mutat Res 459:211–218

    PubMed  CAS  Google Scholar 

  48. Twaroski TP, O’Brien ML, Robertson LW (2001) Effects of selected polychlorinated biphenyl (PCB) congeners on hepatic glutathione, glutathione-related enzymes, and selenium status: implications or oxidative stress. Biochem Pharmacol 62:273–281

    Article  PubMed  CAS  Google Scholar 

  49. Kass GE, Orrenius S (1999) Calcium signaling and cytotoxicity. Environ Health Persp 107:25–35

    CAS  Google Scholar 

  50. Tilson HA, Kodavanti PR (1998) The neurotoxicity of polychlorinated biphenyls. Neurotoxicology 19:571–576

    Google Scholar 

  51. Baliga BC, Kumar S (2002) Role of Bcl-2 family of proteins in malignancy. Hematol Oncol 20:63–74

    Article  PubMed  Google Scholar 

  52. Gross A, McDonnell JM, Korsmeyer SJ (1999) BCL-2 family members and the mitochondria in apoptosis. Gen Develop 13:1899–1911

    Article  CAS  Google Scholar 

  53. Kreuz S, Siegmund D, Rumpf JJ et al (2004) NFkappaB activation by Fas is mediated through FADD, caspase-8, and RIP and is inhibited by FLIP. J Cell Biol 166:369–380

    Article  PubMed  CAS  Google Scholar 

  54. Kaur P, Kaur G, Bansal MP (2006) Tertiary-butyl hydroperoxide induced oxidative stress and male reproductive activity in mice: role of transcription factor NF-kappaB and testicular antioxidant enzymes. Reprod Toxicol 22:479–484

    Article  PubMed  CAS  Google Scholar 

  55. Hofmann MA, Schiekofer S, Isermann B et al (1999) Peripheral blood mononuclear cells isolated from patients with diabetic nephropathy show increased activation of the oxidative stress-sensitive transcription factor NF-kB. Diabetologia 42:222–232

    Article  PubMed  CAS  Google Scholar 

  56. Peet GW, Li J (1999) I KappaB kinases alpha and beta show a random sequential kinetic mechanism and are inhibited by staurosporin and quercetin. J Biol Chem 274:32655–32661

    Article  PubMed  CAS  Google Scholar 

  57. Sánchez-Alonso JA, López-Aparicio P, Recio MN et al (2004) Polychlorinated biphenyl mixtures (Aroclors) induce apoptosis via Bcl-2, Bax and caspase-3 proteins in neuronal cell cultures. Toxicol Lett 153:311–326

    Article  PubMed  Google Scholar 

  58. Venkataraman P, Selvakumar K, Krishnamoorthy G et al (2010) Effect of melatonin on PCB (Aroclor 1254) induced neuronal damage and changes in Cu/Zn superoxide dismutase and glutathione peroxidase-4 mRNA expression in cerebral cortex, cerebellum and hippocampus of adult rats. Neurosci Res 66:189–197

    Article  PubMed  CAS  Google Scholar 

  59. Nagata S (1999) Fas ligand-induced apoptosis. Ann Rev Gene 33:29–55

    Article  CAS  Google Scholar 

  60. Gurel A, Coskun O, Armutcu F et al (2005) Vitamin E against oxidative damage caused by formaldehyde in frontal cortex and hippocampus: biochemical and histological studies. J Chem Neuroanat 29:173–178

    Article  PubMed  CAS  Google Scholar 

  61. Jovanovic SV, Steenkan S, Simic MG et al (1998) Antioxidant properties of flavonoids: reduction potentials and electron transfer reactions of flavonoid radicals. In: Rice Evans C, Packer L (eds) Flavonoids in health and disease. Marcel Dekker, New York, pp 137–161

    Google Scholar 

  62. Kawada N, Seki S, Inoue M et al (1998) Effect of antioxidants, resveratrol, quercetin, and N-acetylcysteine, on the functions of cultured rat hepatic stellate cells and Kupffer cells. Hepatology 27:1265–1274

    Article  PubMed  CAS  Google Scholar 

  63. Huk I, Brovkovich V, Nanobash VJ et al (1998) Bioflavonoid quercetin scavenges superoxide and increases nitric oxide concentration in ischaemia-reperfusion injury: an experimental study. British J Surg 85:1080–1085

    Article  CAS  Google Scholar 

  64. Kumar P, Sharma S, Khanna M et al (2003) Effect of quercetin on lipid peroxidation and changes in lung morphology in experimental influenza virus infection. Int J Exp Pathol 3:127–133

    Article  Google Scholar 

  65. Gschwendt M, Horn F, Kittstein W et al (1983) Inhibition of the calcium- and phospholipid-dependent protein kinase activity from mouse brain cytosol by quercetin. Biochem Biophy Res Comm 117:444–447

    Article  CAS  Google Scholar 

  66. Nishino H, Nishino A, Iwashima A et al (1984) Quercetin interacts with cadmodulin, a calcium regulatory protein. Experientia 40:184–185

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The financial assistance to Mr. K. Selvakumar, Department of Endocrinology from UGC RFSMS programme, New Delhi is gratefully acknowledged.

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The author(s) declared no potential conflicts of interest with respect to the authorship and/or publication of this article.

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Correspondence to Jagadeesan Arunakaran.

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Selvakumar, K., Bavithra, S., Suganthi, M. et al. Protective Role of Quercetin on PCBs-Induced Oxidative Stress and Apoptosis in Hippocampus of Adult Rats. Neurochem Res 37, 708–721 (2012). https://doi.org/10.1007/s11064-011-0661-5

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