Table of Contents Author Guidelines Submit a Manuscript
Evidence-Based Complementary and Alternative Medicine
Volume 2015, Article ID 202874, 18 pages
http://dx.doi.org/10.1155/2015/202874
Research Article

Tualang Honey Protects against BPA-Induced Morphological Abnormalities and Disruption of ERα, ERβ, and C3 mRNA and Protein Expressions in the Uterus of Rats

1Department of Anatomy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
2Department of Environmental Sciences, Faculty of Environmental Studies, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
3Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia

Received 8 September 2015; Accepted 12 November 2015

Academic Editor: Omer Kucuk

Copyright © 2015 Siti Sarah Mohamad Zaid et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. N. Von Goetz, M. Wormuth, M. Scheringer, and K. Hungerbühler, “Bisphenol a: How the most relevant exposure sources contribute to total consumer exposure,” Risk Analysis, vol. 30, no. 3, pp. 473–487, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. Y. B. Wetherill, B. T. Akingbemi, J. Kanno et al., “In vitro molecular mechanisms of bisphenol A action,” Reproductive Toxicology, vol. 24, no. 2, pp. 178–198, 2007. View at Publisher · View at Google Scholar · View at Scopus
  3. A. Suzuki, A. Sugihara, K. Uchida et al., “Developmental effects of perinatal exposure to bisphenol-A and diethylstilbestrol on reproductive organs in female mice,” Reproductive Toxicology, vol. 16, no. 2, pp. 107–116, 2002. View at Publisher · View at Google Scholar · View at Scopus
  4. Y. J. Yang, Y.-C. Hong, S.-Y. Oh et al., “Bisphenol A exposure is associated with oxidative stress and inflammation in postmenopausal women,” Environmental Research, vol. 109, no. 6, pp. 797–801, 2009. View at Publisher · View at Google Scholar · View at Scopus
  5. H.-W. Kuo and W.-H. Ding, “Trace determination of bisphenol A and phytoestrogens in infant formula powders by gas chromatography-mass spectrometry,” Journal of Chromatography A, vol. 1027, no. 1-2, pp. 67–74, 2004. View at Publisher · View at Google Scholar · View at Scopus
  6. Y. Sun, M. Wada, O. Al-Dirbashi, N. Kuroda, H. Nakazawa, and K. Nakashima, “High-performance liquid chromatography with peroxyoxalate chemiluminescence detection of bisphenol A migrated from polycarbonate baby bottles using 4-(4,5-diphenyl-1H-imidazol-2-yl)benzoyl chloride as a label,” Journal of Chromatography B: Biomedical Sciences and Applications, vol. 749, no. 1, pp. 49–56, 2000. View at Publisher · View at Google Scholar
  7. C. Brede, P. Fjeldal, I. Skjevrak, and H. Herikstad, “Increased migration levels of bisphenol A from polycarbonate baby bottles after dishwashing, boiling and brushing,” Food Additives & Contaminants, vol. 20, no. 7, pp. 684–689, 2003. View at Publisher · View at Google Scholar · View at Scopus
  8. J. C. Gould, L. S. Leonard, S. C. Maness et al., “Bisphenol A interacts with the estrogen receptor α in a distinct manner from estradiol,” Molecular and Cellular Endocrinology, vol. 142, no. 1-2, pp. 203–214, 1998. View at Publisher · View at Google Scholar · View at Scopus
  9. M. V. Maffini, B. S. Rubin, C. Sonnenschein, and A. M. Soto, “Endocrine disruptors and reproductive health: the case of bisphenol-A,” Molecular and Cellular Endocrinology, vol. 254-255, pp. 179–186, 2006. View at Publisher · View at Google Scholar · View at Scopus
  10. C. M. Markey, P. R. Wadia, B. S. Rubin, C. Sonnenschein, and A. M. Soto, “Long-term effects of fetal exposure to low doses of the xenoestrogen bisphenol-A in the female mouse genital tract,” Biology of Reproduction, vol. 72, no. 6, pp. 1344–1351, 2005. View at Publisher · View at Google Scholar · View at Scopus
  11. P. Diel, T. Schulz, K. Smolnikar, E. Strunck, G. Vollmer, and H. Michna, “Ability of xeno- and phytoestrogens to modulate estrogen-sensitive genes in rat uterus: estrogenicity profiles and uterotrophic activity,” Journal of Steroid Biochemistry and Molecular Biology, vol. 73, no. 1-2, pp. 1–10, 2000. View at Publisher · View at Google Scholar · View at Scopus
  12. G. Schönfelder, K. Friedrich, M. Paul, and I. Chahoud, “Developmental effects of prenatal exposure to bisphenol A on the uterus of rat offspring,” Neoplasia, vol. 6, no. 5, pp. 584–594, 2004. View at Publisher · View at Google Scholar · View at Scopus
  13. D. Seidlová-Wuttke, H. Jarry, and W. Wuttke, “Pure estrogenic effect of benzophenone-2 (BP2) but not of bisphenol a (BPA) and dibutylphtalate (DBP) in uterus, vagina and bone,” Toxicology, vol. 205, no. 1-2, pp. 103–112, 2004. View at Publisher · View at Google Scholar · View at Scopus
  14. S. Xiao, H. Diao, M. A. Smith, X. Song, and X. Ye, “Preimplantation exposure to bisphenol A (BPA) affects embryo transport, preimplantation embryo development, and uterine receptivity in mice,” Reproductive Toxicology, vol. 32, no. 4, pp. 434–441, 2011. View at Publisher · View at Google Scholar · View at Scopus
  15. T. Kurosawa, H. Hiroi, O. Tsutsumi et al., “The activity of bisphenol A depends on both the estrogen receptor subtype and the cell type,” Endocrine Journal, vol. 49, no. 4, pp. 465–471, 2002. View at Publisher · View at Google Scholar · View at Scopus
  16. H. Kabuto, S. Hasuike, N. Minagawa, and T. Shishibori, “Effects of bisphenol A on the metabolisms of active oxygen species in mouse tissues,” Environmental Research, vol. 93, no. 1, pp. 31–35, 2003. View at Publisher · View at Google Scholar · View at Scopus
  17. O. O. Erejuwa, S. A. Sulaiman, M. S. Wahab, K. N. S. Sirajudeen, M. S. M. D. Salleh, and S. Gurtu, “Antioxidant protection of Malaysian tualang honey in pancreas of normal and streptozotocin-induced diabetic rats,” Annales d'Endocrinologie, vol. 71, no. 4, pp. 291–296, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. S. S. M. Zaid, S. A. Sulaiman, K. N. M. Sirajudeen, and N. H. Othman, “The effects of Tualang honey on female reproductive organs, tibia bone and hormonal profile in ovariectomised rats—animal model for menopause,” BMC Complementary and Alternative Medicine, vol. 10, article 82, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. S. S. Zaid, S. A. Sulaiman, N. H. Othman et al., “Protective effects of Tualang honey on bone structure in experimental postmenopausal rats,” Clinics, vol. 67, no. 7, pp. 779–784, 2012. View at Publisher · View at Google Scholar · View at Scopus
  20. M. Mohamed, S. A. Sulaiman, H. Jaafar, and K. N. Salam, “Antioxidant protective effect of honey in cigarette smoke-induced testicular damage in rats,” International Journal of Molecular Sciences, vol. 12, no. 9, pp. 5508–5521, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. A. A. Ghashm, N. H. Othman, M. N. Khattak, N. M. Ismail, and R. Saini, “Antiproliferative effect of Tualang honey on oral squamous cell carcinoma and osteosarcoma cell lines,” BMC Complementary and Alternative Medicine, vol. 10, article 49, 2010. View at Publisher · View at Google Scholar · View at Scopus
  22. S. N. S. Mohamad, S. H. Ahmad, and H. G. Siew, “Antiproliferative effect of methanolic extraction of Tualang honey on human keloid fibroblasts,” BMC Complementary and Alternative Medicine, vol. 11, no. 82, pp. 1–8, 2011. View at Publisher · View at Google Scholar
  23. S. Ahmed and N. H. Othman, “Review of the medicinal effects of tualang honey and a comparison with Manuka honey,” Malaysian Journal of Medical Sciences, vol. 20, no. 3, pp. 6–13, 2013. View at Google Scholar · View at Scopus
  24. M. Mahaneem, K. N. S. Sirajudeen, M. Swamy, and S. Y. Nik, “Studies on antioxidant properties of Tualang honey,” African Journal of Traditional, Complementary and Alternative Medicines, vol. 7, no. 1, pp. 59–63, 2010. View at Google Scholar
  25. M. I. Khalil, N. Alam, M. Moniruzzaman, S. A. Sulaiman, and S. H. Gan, “henolic acid composition and antioxidant properties of Malaysian honeys,” Journal of Food Science, vol. 76, no. 6, pp. C921–C928, 2011. View at Publisher · View at Google Scholar · View at Scopus
  26. S. Anjum, S. Rahman, M. Kaur et al., “Melatonin ameliorates bisphenol A-induced biochemical toxicity in testicular mitochondria of mouse,” Food and Chemical Toxicology, vol. 49, no. 11, pp. 2849–2854, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. K. Okuda, M. Takiguchi, and S. Yoshihara, “In vivo estrogenic potential of 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene, an active metabolite of bisphenol A, in uterus of ovariectomized rat,” Toxicology Letters, vol. 197, no. 1, pp. 7–11, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. Y. Li, W. Zhang, J. Liu et al., “Prepubertal bisphenol A exposure interferes with ovarian follicle development and its relevant gene expression,” Reproductive Toxicology, vol. 44, pp. 33–40, 2014. View at Publisher · View at Google Scholar · View at Scopus
  29. H. H. Draper and M. Hadley, “Malondialdehyde determination as index of lipid peroxidation,” Methods in Enzymology, vol. 186, pp. 421–431, 1990. View at Publisher · View at Google Scholar · View at Scopus
  30. K. J. Livak and T. D. Schmittgen, “Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method,” Methods, vol. 25, no. 4, pp. 402–408, 2001. View at Publisher · View at Google Scholar · View at Scopus
  31. E. Spreafico, E. Bettini, G. Pollio, and A. Maggi, “Nucleotide sequence of estrogen receptor cDNA from Sprague-Dawley rat,” European Journal of Pharmacology: Molecular Pharmacology, vol. 227, no. 3, pp. 353–356, 1992. View at Publisher · View at Google Scholar · View at Scopus
  32. G. G. J. M. Kuiper, E. Enmark, M. Pelto-Huikko, S. Nilsson, and J.-Å. Gustafsson, “Cloning of a novel estrogen receptor expressed in rat prostate and ovary,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 12, pp. 5925–5930, 1996. View at Publisher · View at Google Scholar · View at Scopus
  33. Y. Misumi, M. Sohda, and Y. Ikehara, “Nucleotide and deduced amino acid sequence of rat complement C3,” Nucleic Acids Research, vol. 18, no. 8, p. 2178, 1990. View at Publisher · View at Google Scholar · View at Scopus
  34. G. G. J. M. Kuiper, B. Carlsson, K. Grandien et al., “Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta,” Endocrinology, vol. 138, no. 3, pp. 863–870, 1997. View at Publisher · View at Google Scholar · View at Scopus
  35. B. Yi, H. Kasai, H.-S. Lee, Y. Kang, J. Y. Park, and M. Yang, “Inhibition by wheat sprout (Triticum aestivum) juice of bisphenol A-induced oxidative stress in young women,” Mutation Research/Genetic Toxicology and Environmental Mutagenesis, vol. 724, no. 1-2, pp. 64–68, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. M. J. Wolfsegger, T. Jaki, B. Dietrich, J. A. Kunzler, and K. Barker, “A note on statistical analysis of organ weights in non-clinical toxicological studies,” Toxicology and Applied Pharmacology, vol. 240, no. 1, pp. 117–122, 2009. View at Publisher · View at Google Scholar · View at Scopus
  37. J. Ashby, H. Tinwell, P. A. Lefevre, R. Joiner, and J. Haseman, “The effect on sperm production in adult Sprague-Dawley rats exposed by gavage to bisphenol A between postnatal days 91–97,” Toxicological Sciences, vol. 74, no. 1, pp. 129–138, 2003. View at Publisher · View at Google Scholar · View at Scopus
  38. C. M. Markey, M. A. Coombs, C. Sonnenschein, and A. M. Soto, “Mammalian development in a changing environment: exposure to endocrine disruptors reveals the developmental plasticity of steroid-hormone target organs,” Evolution and Development, vol. 5, no. 1, pp. 67–75, 2003. View at Publisher · View at Google Scholar · View at Scopus
  39. B. S. Rubin, M. K. Murray, D. A. Damassa, J. C. King, and A. M. Soto, “Perinatal exposure to low doses of bisphenol A affects body weight, patterns of estrous cyclicity, and plasma LH levels,” Environmental Health Perspectives, vol. 109, no. 7, pp. 675–680, 2001. View at Publisher · View at Google Scholar · View at Scopus
  40. K. L. Howdeshell, A. K. Hotchkiss, K. A. Thayer, J. G. Vandenbergh, and F. S. Vom Saal, “Environmental toxins: exposure to bisphenol A advances puberty,” Nature, vol. 401, no. 6755, pp. 763–764, 1999. View at Publisher · View at Google Scholar · View at Scopus
  41. M. Güney, B. Oral, H. Demirin et al., “Evaluation of caspase-dependent apoptosis during methyl parathion-induced endometrial damage in rats: ameliorating effect of vitamins E and C,” Environmental Toxicology and Pharmacology, vol. 23, no. 2, pp. 221–227, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. R. Aslan, M. R. Sekeroglu, M. Tarakcioglu, and H. Koylu, “Investigation of malondialdehyde formation and antioxidant enzyme activity in stored blood,” Haematologia, vol. 28, no. 4, pp. 233–237, 1997. View at Google Scholar · View at Scopus
  43. T. Suzuki, N. Sugino, T. Fukaya et al., “Superoxide dismutase in normal cycling human ovaries: immunohistochemical localization and characterization,” Fertility and Sterility, vol. 72, no. 4, pp. 720–726, 1999. View at Publisher · View at Google Scholar · View at Scopus
  44. M. Jozwik, S. Wolczynski, M. Jozwik, and M. Szamatowicz, “Oxidative stress markers in preovulatory follicular fluid in humans,” Molecular Human Reproduction, vol. 5, no. 5, pp. 409–413, 1999. View at Publisher · View at Google Scholar · View at Scopus
  45. Y. Wang, J. Goldberg, R. K. Sharma, A. Agarwal, and T. Falcone, “Importance of reactive oxygen species in the peritoneal fluid of women with endometriosis or idiopathic infertility,” Fertility and Sterility, vol. 68, no. 5, pp. 826–830, 1997. View at Publisher · View at Google Scholar · View at Scopus
  46. G. Polak, M. Koziol-Montewka, M. Gogacz, I. Blaszkowska, and J. Kotarski, “Total antioxidant status of peritoneal fluid in infertile women,” European Journal of Obstetrics Gynecology and Reproductive Biology, vol. 94, no. 2, pp. 261–263, 2001. View at Publisher · View at Google Scholar · View at Scopus
  47. N. Shafin, Z. Othman, R. Zakaria, and N. H. Nik Hussain, “Tualang honey supplementation reduces blood oxidative stress levels/activities in postmenopausal women,” ISRN Oxidative Medicine, vol. 2014, Article ID 364836, 4 pages, 2014. View at Publisher · View at Google Scholar
  48. A. Atkinson and D. Roy, “In vivo DNA adduct formation by bisphenol A,” Environmental and Molecular Mutagenesis, vol. 26, no. 1, pp. 60–66, 1995. View at Publisher · View at Google Scholar · View at Scopus
  49. J. S. Edmonds, M. Nomachi, M. Terasaki, M. Morita, B. W. Skelton, and A. H. White, “The reaction of bisphenol A 3,4-quinone with DNA,” Biochemical and Biophysical Research Communications, vol. 319, no. 2, pp. 556–561, 2004. View at Publisher · View at Google Scholar · View at Scopus
  50. R. K. Kishore, A. S. Halim, M. S. N. Syazana, and K. N. S. Sirajudeen, “Tualang honey has higher phenolic content and greater radical scavenging activity compared with other honey sources,” Nutrition Research, vol. 31, no. 1, pp. 322–325, 2011. View at Publisher · View at Google Scholar · View at Scopus
  51. B. Oral, M. Guney, H. Demirin et al., “Endometrial damage and apoptosis in rats induced by dichlorvos and ameliorating effect of antioxidant vitamins E and C,” Reproductive Toxicology, vol. 22, no. 4, pp. 783–790, 2006. View at Publisher · View at Google Scholar · View at Scopus
  52. S. S. M. Zaid, S. Othman, and N. M. Kassim, “Potential protective effect of Tualang honey on BPA-induced ovarian toxicity in prepubertal rat,” BMC Complementary and Alternative Medicine, vol. 14, article 509, 12 pages, 2014. View at Publisher · View at Google Scholar
  53. H. W. G. Baker, J. Brindle, D. S. Irvine, and R. J. Aitken, “Protective effect of antioxidants on the impairment of sperm motility by activated polymorphonuclear leukocytes,” Fertility and Sterility, vol. 65, no. 2, pp. 411–419, 1996. View at Google Scholar · View at Scopus
  54. V. Kumar, A. Rani, A. K. Dixit, D. Pratap, and D. Bhatnagar, “A comparative assessment of total phenolic content, ferric reducing-anti-oxidative power, free radical-scavenging activity, vitamin C and isoflavones content in soybean with varying seed coat colour,” Food Research International, vol. 43, no. 1, pp. 323–328, 2010. View at Publisher · View at Google Scholar · View at Scopus
  55. A. S. A. Harabawy and Y. Y. I. Mosleh, “The role of vitamins A, C, E and selenium as antioxidants against genotoxicity and cytotoxicity of cadmium, copper, lead and zinc on erythrocytes of Nile tilapia, Oreochromis niloticus,” Ecotoxicology and Environmental Safety, vol. 104, no. 1, pp. 28–35, 2014. View at Publisher · View at Google Scholar · View at Scopus
  56. A. S. Y. Hounkpatin, R. C. Johnson, P. Guedenon et al., “Protective effects of vitamin C on haematological parameters in intoxicated wistar rats with cadmium, mercury and combined cadmium and mercury,” International Research Journal of Biological Sciences, vol. 1, no. 8, pp. 76–81, 2012. View at Google Scholar
  57. M. Shaban El-Neweshy and Y. Said El-Sayed, “Influence of vitamin C supplementation on lead-induced histopathological alterations in male rats,” Experimental and Toxicologic Pathology, vol. 63, no. 3, pp. 221–227, 2011. View at Publisher · View at Google Scholar · View at Scopus
  58. A. Wattel, S. Kamel, R. Mentaverri et al., “Potent inhibitory effect of naturally occurring flavonoids quercetin and kaempferol on in vitro osteoclastic bone resorption,” Biochemical Pharmacology, vol. 65, no. 1, pp. 35–42, 2003. View at Publisher · View at Google Scholar · View at Scopus
  59. M. Chevallet, E. Wagner, S. Luche, A. Van Dorsselaer, E. Leize-Wagner, and T. Rabilloud, “Regeneration of peroxiredoxins during recovery after oxidative stress: only some overoxidized peroxiredoxins can be reduced during recovery after oxidative stress,” Journal of Biological Chemistry, vol. 278, no. 39, pp. 37146–37153, 2003. View at Publisher · View at Google Scholar · View at Scopus
  60. L. Vigezzi, V. L. Bosquiazzo, L. Kass, J. G. Ramos, M. Muñoz-de-Toro, and E. H. Luque, “Developmental exposure to bisphenol A alters the differentiation and functional response of the adult rat uterus to estrogen treatment,” Reproductive Toxicology, vol. 52, no. 1, pp. 83–92, 2015. View at Publisher · View at Google Scholar
  61. C. M. Klinge, “Estrogen receptor interaction with estrogen response elements,” Nucleic Acids Research, vol. 29, no. 14, pp. 2905–2919, 2001. View at Publisher · View at Google Scholar · View at Scopus
  62. H. Hiroi, O. Tsutsumi, M. Momoeda, Y. Takai, Y. Osuga, and Y. Taketani, “Differential interactions of bisphenol A and 17beta-estradiol with estrogen receptor alpha (ERalpha) and ERbeta,” Endocrine Journal, vol. 46, no. 6, pp. 773–778, 1999. View at Publisher · View at Google Scholar · View at Scopus
  63. J. F. Couse and K. S. Korach, “Estrogen receptor null mice: what have we learned and where will they lead us?” Endocrine Reviews, vol. 20, no. 3, pp. 358–417, 1999. View at Publisher · View at Google Scholar · View at Scopus
  64. P. Pace, J. Taylor, S. Suntharalingam, R. C. Coombes, and S. Ali, “Human estrogen receptor β binds DNA in a manner similar to and dimerizes with estrogen receptor α,” Journal of Biological Chemistry, vol. 272, no. 41, pp. 25832–25838, 1997. View at Publisher · View at Google Scholar · View at Scopus
  65. K. Paech, P. Webb, G. G. J. M. Kuiper et al., “Differential ligand activation of estrogen receptors ERα and ERβ at AP1 sites,” Science, vol. 277, no. 5331, pp. 1508–1510, 1997. View at Publisher · View at Google Scholar · View at Scopus
  66. J. J. Voegel, M. J. S. Heine, C. Zechel, P. Chambon, and H. Gronemeyer, “TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors,” The EMBO Journal, vol. 15, no. 14, pp. 3667–3675, 1996. View at Google Scholar · View at Scopus
  67. E. J. Routledge, R. White, M. G. Parker, and J. P. Sumpter, “Differential effects of xenoestrogens on coactivator recruitment by estrogen receptor (ER) α and ERβ,” Journal of Biological Chemistry, vol. 275, no. 46, pp. 35986–35993, 2000. View at Publisher · View at Google Scholar · View at Scopus
  68. Z. Weihua, S. Saji, S. Mäkinen et al., “Estrogen receptor (ER) beta, a modulator of ERalpha in the uterus,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 11, pp. 5936–5941, 2000. View at Publisher · View at Google Scholar · View at Scopus
  69. J. M. Hall and D. P. McDonnel, “The estrogen receptor β-isoform (ERβ) of the human estrogen receptor modulates ERα transcriptional activity and is a key regulator of the cellular response to estrogens and antiestrogens,” Endocrinology, vol. 140, no. 12, pp. 5566–5578, 1999. View at Google Scholar · View at Scopus
  70. K. Pettersson, K. Grandien, G. G. J. M. Kuiper, and J.-Å. Gustafsson, “Mouse estrogen receptor β forms estrogen response element-binding heterodimers with estrogen receptor α,” Molecular Endocrinology, vol. 11, no. 10, pp. 1486–1496, 1997. View at Publisher · View at Google Scholar · View at Scopus
  71. A. Matsushima, Y. Kakuta, T. Teramoto et al., “Structural evidence for endocrine disruptor bisphenol A binding to human nuclear receptor ERRγ,” Journal of Biochemistry, vol. 142, no. 4, pp. 517–524, 2007. View at Publisher · View at Google Scholar · View at Scopus
  72. T. Nose and Y. Shimohigashi, “A docking modelling rationally predicts strong binding of bisphenol A to estrogen-related receptor γ,” Protein and Peptide Letters, vol. 15, no. 3, pp. 290–296, 2008. View at Publisher · View at Google Scholar · View at Scopus
  73. V. Giguère, “To ERR in the estrogen pathway,” Trends in Endocrinology and Metabolism, vol. 13, no. 5, pp. 220–225, 2002. View at Publisher · View at Google Scholar · View at Scopus
  74. S. Takayanagi, T. Tokunaga, X. Liu, H. Okada, A. Matsushima, and Y. Shimohigashi, “Endocrine disruptor bisphenol A strongly binds to human estrogen-related receptor gamma (ERRgamma) with high constitutive activity,” Toxicology Letters, vol. 167, no. 2, pp. 95–105, 2006. View at Publisher · View at Google Scholar · View at Scopus
  75. J. Huppunen and P. Aarnisalo, “Dimerization modulates the activity of the orphan nuclear receptor ERRα,” Biochemical and Biophysical Research Communications, vol. 314, no. 4, pp. 964–970, 2004. View at Publisher · View at Google Scholar · View at Scopus
  76. A. Sahu and J. D. Lambris, “Structure and biology of complement protein C3, a connecting link between innate and acquired immunity,” Immunological Reviews, vol. 180, no. 1, pp. 35–48, 2001. View at Publisher · View at Google Scholar · View at Scopus
  77. S. S. Zaid, S. Othman, and N. M. Kassim, “Potential protective effect of Tualang honey on BPA-induced ovarian toxicity in prepubertal rat,” BMC Complementary and Alternative Medicine, vol. 14, article 509, 2014. View at Publisher · View at Google Scholar
  78. M. G. L. Hertog, P. C. H. Hollman, M. B. Katan, and D. Kromhout, “Intake of potentially anticarcinogenic flavonoids and their determinants in adults in The Netherlands,” Nutrition and Cancer, vol. 20, no. 1, pp. 21–29, 1993. View at Publisher · View at Google Scholar · View at Scopus
  79. D. Tiwari, J. Kamble, S. Chilgunde et al., “Clastogenic and mutagenic effects of bisphenol A: an endocrine disruptor,” Mutation Research: Genetic Toxicology and Environmental Mutagenesis, vol. 743, no. 1-2, pp. 83–90, 2012. View at Publisher · View at Google Scholar · View at Scopus
  80. T. Iso, T. Watanabe, T. Iwamoto, A. Shimamoto, and Y. Furuichi, “DNA damage caused by bisphenol A and estradiol through estrogenic activity,” Biological and Pharmaceutical Bulletin, vol. 29, no. 2, pp. 206–210, 2006. View at Publisher · View at Google Scholar · View at Scopus
  81. H.-J. Wu, C. Liu, W.-X. Duan et al., “Melatonin ameliorates bisphenol A-induced DNA damage in the germ cells of adult male rats,” Mutation Research, vol. 752, no. 1-2, pp. 57–67, 2013. View at Publisher · View at Google Scholar · View at Scopus
  82. N. S. Yaacob and N. F. Ismail, “Comparison of cytotoxicity and genotoxicity of 4-hydroxytamoxifen in combination with Tualang honey in MCF-7 and MCF-10A cells,” BMC Complementary and Alternative Medicine, vol. 14, article 106, 2014. View at Publisher · View at Google Scholar · View at Scopus
  83. I. Ahmad, H. Jimenez, N. S. Yaacob, and N. Yusuf, “Tualang honey protects keratinocytes from ultraviolet radiation-induced inflammation and DNA damage,” Photochemistry and Photobiology, vol. 88, no. 5, pp. 1198–1204, 2012. View at Publisher · View at Google Scholar · View at Scopus
  84. N. S. Yaacob, A. Nengsih, and M. N. Norazmi, “Tualang honey promotes apoptotic cell death induced by tamoxifen in breast cancer cell lines,” Evidence-Based Complementary and Alternative Medicine, vol. 2013, Article ID 989841, 9 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  85. J. Zhou, P. Li, N. Cheng et al., “Protective effects of buckwheat honey on DNA damage induced by hydroxyl radicals,” Food and Chemical Toxicology, vol. 50, no. 8, pp. 2766–2773, 2012. View at Publisher · View at Google Scholar · View at Scopus
  86. H. M. Habib, F. T. Al Meqbali, H. Kamal, U. D. Souka, and W. H. Ibrahim, “Bioactive components, antioxidant and DNA damage inhibitory activities of honeys from arid regions,” Food Chemistry, vol. 153, pp. 28–34, 2014. View at Publisher · View at Google Scholar · View at Scopus