Combined Effects of Repeated Administration of 2,3,7,8-Tetrachlorodibenzo-p-dioxin and Polychlorinated Biphenyls on Kidneys of Male Rats

  • Chun-Feng Lu
  • Yi-Mei Wang
  • Shuang-Qing Peng
  • Li-Bo Zou
  • De-Hong Tan
  • Gang Liu
  • Ze Fu
  • Qiao-Xu Wang
  • Jing Zhao
Article

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) are persistent environmental contaminants that exist as complex mixtures in the environment, but the possible interactions of TCDD and PCBs have not been systematically investigated. The main objective of this study was to investigate the combined nephrotoxic effects of TCDD and PCBs on rats and to reveal the potential interactions between TCDD and PCBs. Male Sprague–Dawley rats were intragastrically administered TCDD (10 μg/kg), PCBs (Aroclor 1254, 10 mg/kg), or the combination (10 μg/kg TCDD + 10 mg/kg Aroclor 1254). After 12 consecutive days of exposure, all treatments induced nephrotoxicity, as evidenced by significant increases in the levels of serum creatinine and blood urea nitrogen, changes of kidney histopathology, and significant renal oxidative stress. Most of these effects were more remarkable in the combined-exposure group. Furthermore, all treatments induced renal cytochrome P450 1A1 (CYP1A1) protein expression, and the induction was more conspicuous in the combined-exposure group. These findings suggested that the nephrotoxicity induced by TCDD and PCBs in the present study might be attributable to the high expression of CYP1A1. In addition, the result of the two-way analysis of variance revealed that the combined effects of TCDD and PCBs were complicated, being additive, synergistic, or antagonistic depending on the selection of toxicity end points under the present experimental condition. This study demonstrates that combined exposure to TCDD and PCBs induced significant nephrotoxicity in rats, and there were complicated interactions between the two pollutants on the nephrotoxicity.

Keywords

PCBs TCDD Nephrotoxicity Combine Group Aryl Hydrocarbon Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgment

This work was supported by the China National Scientific Supporting Program (2006BAK02A02).

References

  1. Ahmed S, Shibazaki M, Takeuchi T, Kikuchi H (2005) Protein kinase Ctheta activity is involved in the 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced signal transduction pathway leading to apoptosis in L-MAT, a human lymphoblastic T-cell line. FEBS J 272:903–915. doi: 10.1111/j.1742-4658.2004.04519.x CrossRefGoogle Scholar
  2. Alsharif NZ, Lawson T, Stohs SJ (1994) Oxidative stress induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin is mediated by the aryl hydrocarbon (Ah) receptor complex. Toxicology 92:39–51. doi: 10.1016/0300-483X(94)90166-X CrossRefGoogle Scholar
  3. Baba T, Mimura J, Nakamura N, Harada N, Yamamoto M, Morohashi K, Fujii-Kuriyama Y (2005) Intrinsic function of the aryl hydrocarbon (dioxin) receptor as a key factor in female reproduction. Mol Cell Biol 25:10040–10051. doi: 10.1128/MCB.25.22.10040-10051.2005 CrossRefGoogle Scholar
  4. Bertazzi PA, Consonni D, Bachetti S, Rubagotti M, Baccarelli A, Zocchetti C, Pesatori AC (2001) Health effects of dioxin exposure: a 20-year mortality study. Am J Epidemiol 153:1031–1044. doi: 10.1093/aje/153.11.1031 CrossRefGoogle Scholar
  5. Birnbaum LS (1994) Evidence for the role of the Ah receptor in response to dioxin. Prog Clin Biol Res 387:139–154Google Scholar
  6. Boutros PC, Moffat ID, Franc MA, Tijet N, Tuomisto J, Pohjanvirta R, Okey AB (2004) Dioxin-responsive AHRE-II gene battery: identification by phylogenetic footprinting. Biochem Biophys Res Commun 321:707–715. doi: 10.1016/j.bbrc.2004.06.177 CrossRefGoogle Scholar
  7. Boverhof DR, Burgoon LD, Tashiro C, Sharratt B, Chittim B, Harkema JR, Mendrick DL, Zacharewski TR (2006) Comparative toxicogenomic analysis of the hepatotoxic effects of TCDD in Sprague Dawley rats and C57BL/6 mice. Toxicol Sci 94:398–416. doi: 10.1093/toxsci/kfl100 CrossRefGoogle Scholar
  8. Chen ZH, Hurh YJ, Na HK, Kim JH, Chun YJ, Kim DH, Kang KS, Cho MH, Surh YJ (2004) Resveratrol inhibits TCDD-induced expression of CYP1A1 and CYP1B1 and catechol estrogen-mediated oxidative DNA damage in cultured human mammary epithelial cells. Carcinogenesis 25:2005–2013. doi: 10.1093/carcin/bgh183 CrossRefGoogle Scholar
  9. Chu I, Lecavalier P, Hakansson H, Yagminas A, Valli VE, Poon P, Feeley M (2001) Mixture effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and polychlorinated biphenyls congeners in rats. Chemosphere 43:807–814. doi: 10.1016/S0045-6535(00)00437-9 CrossRefGoogle Scholar
  10. Chubb LS, Andersen ME, Broccardo CJ, Legare ME, Billings RE, Dean CE, Hanneman WH (2004) Regional induction of CYP1A1 in rat liver following treatment with mixtures of PCB 126 and PCB 153. Toxicol Pathol 32:467–473. doi: 10.1080/01926230490483306 CrossRefGoogle Scholar
  11. Cole P, Trichopoulos D, Pastides H, Starr T, Mandel JS (2003) Dioxin and cancer: a critical review. Regul Toxicol Pharmacol 38:378–388. doi: 10.1016/j.yrtph.2003.08.002 CrossRefGoogle Scholar
  12. Desaulniers D, Cooke GM, Leingartner K, Soumano K, Cole J, Yang J, Wade M, Yagminas A (2005) Effects of postnatal exposure to a mixture of polychlorinated biphenyls, p,p′-dichlorodiphenyltrichloroethane, and p-p′-dichlorodiphenyldichloroethene in prepubertal and adult female Sprague-Dawley rats. Int J Toxicol 24:111–127. doi: 10.1080/10915810590936382 CrossRefGoogle Scholar
  13. Domingo JL, Agramunt MC, Nadal M, Schuhmacher M, Corbella J (2002) Health risk assessment of PCDD/PCDF exposure for the population living in the vicinity of a municipal waste incinerator. Arch Environ Contam Toxicol 43:461–465. doi: 10.1007/s00244-002-1280-6 CrossRefGoogle Scholar
  14. Fletcher N, Wahlström D, Lundberg R, Nilsson CB, Nilsson KC, Stockling K, Hellmold H, Hakansson H (2005) 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters the mRNA expression of critical genes associated with cholesterol metabolism, bile acid biosynthesis, and bile transport in rat liver: a microarray study. Toxicol Appl Pharmacol 207:1–24. doi: 10.1016/j.taap.2004.12.003 CrossRefGoogle Scholar
  15. Fujii-Kuriyama Y, Mimura J (2005) Molecular mechanisms of AhR functions in the regulation of cytochrome P450 genes. Biochem Biophys Res Commun 338:311–317. doi: 10.1016/j.bbrc.2005.08.162 CrossRefGoogle Scholar
  16. Gauger KJ, Giera S, Sharlin DS, Bansal R, Iannacone E, Zoeller RT (2007) Polychlorinated biphenyls 105 and 118 form thyroid hormone receptor agonists after cytochrome P4501A1 activation in rat pituitary GH3 cells. Environ Health Perspect 115:1623–1630Google Scholar
  17. Hassoun EA, Wang H, Abushaban A, Stohs SJ (2002) Induction of oxidative stress in the tissues of rats after chronic exposure to TCDD, 2,3,4,7,8-pentachlorodibenzofuran, and 3,3′,4,4′,5-pentachlorobiphenyl. J Toxicol Environ Health A 65:825–842. doi: 10.1080/00984100290071054 CrossRefGoogle Scholar
  18. Jin MH, Ko HK, Hong CH, Han SW (2008) In utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin affects the development of reproductive system in mouse. Yonsei Med J 49:843–850. doi: 10.3349/ymj.2008.49.5.843 CrossRefGoogle Scholar
  19. Kannan N, Tanabe S, Ono M, Tatsukawa R (1989) Critical evaluation of polychlorinated biphenyl toxicity in terrestrial and marine mammals: increasing impact of non-ortho and mono-ortho coplanar polychlorinated biphenyls from land to ocean. Arch Environ Contam Toxicol 18:850–857. doi: 10.1007/BF01160300 CrossRefGoogle Scholar
  20. Kern PA, Fishman RB, Song W, Brown AD, Fonseca V (2002) The effect of 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) on oxidative enzymes in adipocytes and liver. Toxicology 171:117–125. doi: 10.1016/S0300-483X(01)00564-9 CrossRefGoogle Scholar
  21. Knerr S, Schaefer J, Both S, Mally A, Dekant W, Schrenk D (2006) 2,3,7,8-Tetrachlorodibenzo-p-dioxin induced cytochrome P450 s alter the formation of reactive oxygen species in liver cells. Mol Nutr Food Res 50:378–384. doi: 10.1002/mnfr.200500183 CrossRefGoogle Scholar
  22. Korenaga T, Fukusato T, Ohta M, Asaoka K, Murata N, Arima A, Kubota S (2007) Long-term effects of subcutaneously injected 2,3,7,8-tetrachlorodibenzo-p-dioxin on the liver of rhesus monkeys. Chemosphere 67:S399–S404. doi: 10.1016/j.chemosphere.2006.05.135 CrossRefGoogle Scholar
  23. Latchoumycandane C, Chitra KC, Mathur PP (2002) The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the antioxidant system in mitochondrial and microsomal fractions of rat testis. Toxicology 171:127–135. doi: 10.1016/S0300-483X(01)00563-7 CrossRefGoogle Scholar
  24. Leung YK, Lau KM, Mobley J, Jiang Z, Ho SM (2005) Overexpression of cytochrome P450 1A1 and its novel spliced variant in ovarian cancer cells: alternative subcellular enzyme compartmentation may contribute to carcinogenesis. Cancer Res 65:3726–3734. doi: 10.1158/0008-5472.CAN-04-3771 CrossRefGoogle Scholar
  25. Lin PH, Lin CH, Huang CC, Chuang MC, Lin P (2007) 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces oxidative stress, DNA strand breaks, and poly (ADP-ribose) polymerase-1 activation in human breast carcinoma cell lines. Toxicol Lett 172:146–158. doi: 10.1016/j.toxlet.2007.06.003 CrossRefGoogle Scholar
  26. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275Google Scholar
  27. Marlowe JL, Puga A (2005) Aryl hydrocarbon receptor, cell cycle regulation, toxicity, and tumorigenesis. J Cell Biochem 96:1174–1184. doi: 10.1002/jcb.20656 CrossRefGoogle Scholar
  28. McLean MR, Twaroski TP, Robertson LW (2000) Redox cycling of 2-(x′-mono, -di, -trichlorophenyl)-1,4-benzoquinones, oxidation products of polychlorinated biphenyls. Arch Biochem Biophys 376:449–455. doi: 10.1006/abbi.2000.1754 CrossRefGoogle Scholar
  29. Moennikes O, Loeppen S, Buchmann A, Andersson P, Ittrich C, Poellinger L, Schwarz M (2004) A constitutively active dioxin/aryl hydrocarbon receptor promotes hepatocarcinogenesis in mice. Cancer Res 64:4707–4710. doi: 10.1158/0008-5472.CAN-03-0875 CrossRefGoogle Scholar
  30. Moron MS, Depierre JW, Mannervik B (1979) Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta 582:67–78Google Scholar
  31. Morrissey RE, Harris MW, Diliberto JJ, Birnbaum LS (1992) Limited PCB antagonism of TCDD-induced malformations in mice. Toxicol Lett 60:19–25. doi: 10.1016/0378-4274(92)90043-J CrossRefGoogle Scholar
  32. Murugesan P, Senthilkumar J, Balasubramanian K, Aruldhas MM, Arunakaran J (2005) Impact of polychlorinated biphenyl Aroclor 1254 on testicular antioxidant system in adult rats. Hum Exp Toxicol 24:61–66. doi: 10.1191/0960327105ht500oa CrossRefGoogle Scholar
  33. Muthuvel R, Venkataraman P, Krishnamoorthy G, Gunadharini DN, Kanagaraj P, Stanley AJ, Srinivasan N, Balasubramanian K, Aruldhas MM, Arunakaran J (2006) Antioxidant effect of ascorbic acid on PCB (Aroclor 1254) induced oxidative stress in hypothalamus of albino rats. Clin Chim Acta 365:297–303. doi: 10.1016/j.cca.2005.09.006 CrossRefGoogle Scholar
  34. Nagayama J, Tsuji H, Iida T, Nakagawa R, Matsueda T, Hirakawa H, Yanagawa T, Fukushige J, Watanabe T (2007) Immunologic effects of perinatal exposure to dioxins, PCBs and organochlorine pesticides in Japanese infants. Chemosphere 67:S393–S398. doi: 10.1016/j.chemosphere.2006.05.134 CrossRefGoogle Scholar
  35. Nebert DW, Dalton TP, Okey AB, Gonzalez FJ (2004) Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer. J Biol Chem 279:23847–23850. doi: 10.1074/jbc.R400004200 CrossRefGoogle Scholar
  36. Nebert DW, Roe AL, Dieter MZ, Solis WA, Yang Y, Dalton TP (2000) Role of the aromatic hydrocarbon receptor and [Ah] gene battery in the oxidative stress response, cell cycle control, and apoptosis. Biochem Pharmacol 59:65–85. doi: 10.1016/S0006-2952(99)00310-X CrossRefGoogle Scholar
  37. Ohbayashi H, Sasaki T, Matsumoto M, Noguchi T, Yamazaki K, Aiso S, Nagano K, Arito H, Yamamoto S (2007) Dose- and time-dependent effects of 2,3,7,8-tetrabromodibenzo-p-dioxin on rat liver. J Toxicol Sci 32:47–56. doi: 10.2131/jts.32.47 CrossRefGoogle Scholar
  38. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358. doi: 10.1016/0003-2697(79)90738-3 CrossRefGoogle Scholar
  39. Pollenz RS (2002) The mechanism of AH receptor protein down-regulation (degradation) and its impact on AH receptor-mediated gene regulation. Chem Biol Interact 141:41–61. doi: 10.1016/S0009-2797(02)00065-0 CrossRefGoogle Scholar
  40. Reichard JF, Dalton TP, Shertzer HG, Puga A (2005) Induction of oxidative stress responses by dioxin and other ligands of the aryl hydrocarbon receptor. Dose Response 3:306–331. doi: 10.2203/dose-response.003.03.003 CrossRefGoogle Scholar
  41. Safe S (1990) Polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and related compounds: environmental and mechanistic considerations which support the development of toxic equivalency factors (TEFs). Crit Rev Toxicol 21:51–88CrossRefGoogle Scholar
  42. Safe S (1993) Toxicology, structure-function relationship, and human and environmental health impacts of polychlorinated biphenyls: progress and problems. Environ Health Perspect 100:259–268. doi: 10.2307/3431532 CrossRefGoogle Scholar
  43. Safe SH (1994) Polychlorinated biphenyls (PCBs): environmental impact, biochemical and toxic responses, and implications for risk assessment. Crit Rev Toxicol 24:87–149. doi: 10.3109/10408449409049308 CrossRefGoogle Scholar
  44. Sridevi N, Venkataraman P, Senthilkumar K, Krishnamoorthy G, Arunakaran J (2007) Oxidative stress modulates membrane bound ATPases in brain regions of PCB (Aroclor 1254) exposed rats: protective role of alpha-tocopherol. Biomed Pharmacother 61:435–440CrossRefGoogle Scholar
  45. Star RA (1998) Treatment of acute renal failure. Kidney Int 54:1817–1831. doi: 10.1046/j.1523-1755.1998.00210.x CrossRefGoogle Scholar
  46. Tijet N, Boutros PC, Moffat ID, Okey AB, Tuomisto J, Pohjanvirta R (2006) Aryl hydrocarbon receptor regulates distinct dioxin-dependent and dioxin-independent gene batteries. Mol Pharmacol 69:140–153Google Scholar
  47. Tilson HA, Kodavanti PR (1998) The neurotoxicity of polychlorinated biphenyls. Neurotoxicology 19:517–525Google Scholar
  48. Twaroski TP, O’Brien ML, Larmonier N, Glauert HP, Robertson LW (2001) Polychlorinated biphenyl-induced effects on metabolic enzymes, AP-1 binding, vitamin E, and oxidative stress in the rat liver. Toxicol Appl Pharmacol 171:85–93. doi: 10.1006/taap.2000.9114 CrossRefGoogle Scholar
  49. Van Birgelen AP, Van der Kolk J, Fase KM, Bol I, Poiger H, Brouwer A, Van den Berg M (1994a) Toxic potency of 3,3′,4,4′,5-pentachlorobiphenyl relative to and in combination with 2,3,7,8-tetrachlorodibenzo-p-dioxin in a subchronic feeding study in the rat. Toxicol Appl Pharmacol 127:209–221. doi: 10.1006/taap.1994.1155 CrossRefGoogle Scholar
  50. Van Birgelen AP, Van der Kolk J, Fase KM, Bol I, Poiger H, Van den Berg M, Brouwer A (1994b) Toxic potency of 2,3,3′,4,4′,5-hexachlorobiphenyl relative to and in combination with 2,3,7,8-tetrachlorodibenzo-p-dioxin in a subchronic feeding study in the rat. Toxicol Appl Pharmacol 126:202–213. doi: 10.1006/taap.1994.1109 CrossRefGoogle Scholar
  51. Venkataraman P, Muthuvel R, Krishnamoorthy G, Arunkumar A, Sridhar M, Srinivasan N, Balasubramanian K, Aruldhas MM, Arunakaran J (2007) PCB (Aroclor 1254) enhances oxidative damage in rat brain regions: protective role of ascorbic acid. Neurotoxicology 28:490–498. doi: 10.1016/j.neuro.2006.11.002 CrossRefGoogle Scholar
  52. Wade MG, Foster WG, Younglai EV, McMahon A, Leingartner K, Yagminas A, Blakey D, Fournier M, Desaulniers D, Hughes CL (2002) Effects of subchronic exposure to a complex mixture of persistent contaminants in male rats: systemic, immune, and reproductive effects. Toxicol Sci 67:131–143. doi: 10.1093/toxsci/67.1.131 CrossRefGoogle Scholar
  53. Walker NJ, Crockett PW, Nyska A, Brix AE, Jokinen MP, Sells DM, Hailey JR, Easterling M, Haseman JK, Yin M, Wyde ME, Bucher JR, Portier CJ (2005) Dose-additive carcinogenicity of a defined mixture of “dioxin-like compounds”. Environ Health Perspect 113:43–48CrossRefGoogle Scholar
  54. Wang BY (2001) Pathologic techniques. People’s Healthy Press, Beijing, pp 128–134; in ChineseGoogle Scholar
  55. Xu L, Li AP, Kaminski DL, Ruh MF (2000) 2,3,7,8 Tetrachlorodibenzo-p-dioxin induction of cytochrome P4501A in cultured rat and human hepatocytes. Chem Biol Interact 124:173–189. doi: 10.1016/S0009-2797(99)00149-0 CrossRefGoogle Scholar
  56. Zoeller RT, Dowling AL, Vas AA (2000) Developmental exposure to polychlorinated biphenyls exerts thyroid hormone-like effects on the expression of RC3/neurogranin and myelin basic protein messenger ribonucleic acids in the developing rat brain. Endocrinology 141:181–189. doi: 10.1210/en.141.1.181 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Chun-Feng Lu
    • 1
    • 2
    • 3
  • Yi-Mei Wang
    • 1
  • Shuang-Qing Peng
    • 1
  • Li-Bo Zou
    • 2
  • De-Hong Tan
    • 2
  • Gang Liu
    • 1
  • Ze Fu
    • 1
  • Qiao-Xu Wang
    • 1
  • Jing Zhao
    • 1
  1. 1.Evaluation and Research Center for ToxicologyInstitute of Disease Control and Prevention of PLA, Academy of Military Medical SciencesBeijingPeople’s Republic of China
  2. 2.Department of PharmacologyShenyang Pharmaceutical UniversityShenyangPeople’s Republic of China
  3. 3.Department of Pharmacology, Basic Medical CollegeJiamusi UniversityJiamusiPeople’s Republic of China

Personalised recommendations