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Environmental Science and Pollution Research

, Volume 24, Issue 34, pp 26724–26733 | Cite as

Protective effect of proanthocyanidin on mice Sertoli cell apoptosis induced by zearalenone via the Nrf2/ARE signalling pathway

  • Miao Long
  • Shu-Hua Yang
  • Wei Shi
  • Peng Li
  • Yang Guo
  • Jiayi Guo
  • Jian-Bin He
  • Yi ZhangEmail author
Research Article

Abstract

This study evaluated the protective effect of proanthocyanidin (PC) on the cytotoxicity of the Sertoli cell TM4 of mice, as induced by zearalenone (ZEA). Flow cytometry was used to detect the apoptosis rate of cells in each group. The activities of antioxidant enzymes and the content of antioxidant substances were detected by using a proprietary kit; the RT-PCR method was used to detect the expression level of mRNA, the related genes of Nrf2/ARE signal pathway, the nuclear factor E2 related factor 2 (Nrf2), heme oxygenase 1 (HO-1), glutathione peroxidase (GSH-Px), quinone oxidoreductase 1 (NQO1), γ-glutamylcysteine synthetase (γ-GCS) and the expression level of mRNA, the apoptosis-related genes, Bcl-2 and Bax; the Western-blot method was used to detect the protein expression levels of Nrf2, GSH-Px, HO-1, γ-GCS and NQO1 in each group. Our results showed that PC could reduce the apoptosis rate of the TM4 cells exposed to ZEA (p < 0.01); PC could enhance the decrease in the activities of T-SOD and GSH-Px induced by ZEA (p < 0.05), reduce the increase in the content of MDA, as caused by ZEA; PC could significantly up-regulate the down-regulation levels of the mRNA and protein of Nrf2, GSH-Px, HO-1, γ-GCS and NQO1 induced by ZEA. PC could enhance the decrease in the mRNA expression level of Bcl-2 and down-regulate the mRNA expression of Bax induced by ZEA (p < 0.05). These results demonstrated that PC conferred protective effects against oxidative damage and apoptosis of TM4 cells induced by ZEA. The protection mechanism of PC on TM4 cells might act through the activation of the Nrf2/ARE signalling pathway.

Keywords

Proanthocyanidins Zearalenone TM4 cell Cell apoptosis Oxidative damage Nrf2/ARE signalling pathway 

Notes

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (grant No. 31640084; grant No. 31772809; grant No. 31302152; grant No. 31201961)

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

References

  1. Alshannaq A, Yu JH (2017) Occurrence, toxicity, and analysis of major mycotoxins in food. Int J environ res public health. 14(6). Pii: E632.  https://doi.org/10.3390/ijerph14060632
  2. Aruoma OI, Sun B, Fujii H, Neergheen VS, Bahorun T, Kang KS (2006) Low molecular proanthocyanidin dietary biofactor Oligonol: its modulation of oxidative stress, bioefficacy, neuroprotection, food application and chemoprevention potentials. Biofactors 27(1–4):245–265CrossRefGoogle Scholar
  3. Avelar MM, Gouvêa CM (2012) Procyanidin b2 cytotoxicity to mcf-7 human breast adenocarcinoma cells. Indian J Pharm Sci 74(4):351–355CrossRefGoogle Scholar
  4. Bagchi D, Garg A, Krohn RL, Bagchi M, Tran MX, Stohs SJ (1997) Oxygen free radical scavenging abilities of vitamins C and E, and a grape seed proanthocyanidin extract in vitro. Res Commun Mol Pathol Pharmacol 95:179–189Google Scholar
  5. Belhassen H, Jiménez-Díaz I, Arrebola JP, Ghali R, Ghorbel H, Olea N (2015) Zearalenone and its metabolites in urine and breast cancer risk: a case-control study in Tunisia. Chemosphere 128:1–6CrossRefGoogle Scholar
  6. Ben Salem I, Prola A, Boussabbeh M, Guilbert A, Bacha H, Lemaire CAbid-Essefi S (2016) Activation of ER stress and apoptosis by α- and β-zearalenol in HCT116 cells, protective role of quercetin. Neurotoxicology 53:334–342Google Scholar
  7. Chang P, Mo B, Cauvi DM, Yu Y, Guo Z, Zhou J (2017) Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis. Peer J 5:e3108CrossRefGoogle Scholar
  8. Chojnacka K, Zarzycka M, Mruk DD (2016) Biology of the Sertoli cell in the fetal, pubertal, and adult mammalian testis. Results Probl Cell Differ 58:225–251CrossRefGoogle Scholar
  9. Chu P, Li H, Luo R, Ahsan A, Qaed E, Shopit A (2017) Oleanolic acid derivative SZC014 inhibit cell proliferation and induce apoptosis of human breast cancer cells in a ROS-dependent way. Neoplasma.  https://doi.org/10.4149/neo_2017_505 [Epub ahead of print]
  10. Fan W, Shen T, Ding Q, Lv Y, Li L, Huang K (2017) Zearalenone induces ROS-mediated mitochondrial damage in porcine IPEC-J2 cells. J Biochem Mol Toxicol.  https://doi.org/10.1002/jbt.21944 [Epub ahead of print]
  11. Gajecdi M, Przybylowicz M, Zielonka L, Zwierzchowski W, Obremski K, Skorska-Wyszyńska E (2004) Preliminary results of manitoring research on zearalenone presence in blood of women with neoplastic lesions in reproductive system. Pol J Vet Sei 7(2): 153–156Google Scholar
  12. Hou F, Xiao M, Li J, Cook DW, Zeng W, Zhang C (2016) Ameliorative effect of grape seed proanthocyanidin extract on cadmium-induced meiosis inhibition during oogenesis in chicken embryos. Anat Rec (Hoboken) 299(4):450–460CrossRefGoogle Scholar
  13. Hu J, Xu M, Dai Y, Ding X, Xiao C, Ji H (2016) Exploration of Bcl-2 family and caspases-dependent apoptotic signaling pathway in zearalenone-treated mouse endometrial stromal cells. Biochem Biophys Res Commun 476(4):553–559CrossRefGoogle Scholar
  14. Kakeya H, Takahashi-Ando N, Kimura M, Onose R, Yamaguchi I, Osada H (2002) Biotransformation of the mycotoxin, zearalenone, to a non-esrtogenic compound by a fungal strain of Clonostachys sp. Biosci Biotechnol Biochem 66(12):2723–2726CrossRefGoogle Scholar
  15. Kordic B, Pribicevic S, Munt anola-Cvetkovic M, Nikolić P, Nikolić B (1992) Experimental study of the effects of known quantities of zearalenone on swine reproduction. J Environ Pathol Toxicol Oncol 11(2):53–55Google Scholar
  16. Kowalska K, Habrowska-Górczyńska DE, Domińska K, Piastowska-Ciesielska AW (2017) The dose-dependent effect of zearalenone on mitochondrial metabolism, plasma membrane permeabilization and cell cycle in human prostate cancer cell lines. Chemosphere 180:455–466CrossRefGoogle Scholar
  17. Li S, Xu M, Niu Q, Xu S, Ding Y, Yan Y (2015) Efficacy of procyanidins against in vivo cellular oxidative damage: a systematic review and meta-analysis. PLoS One 10:e0139455CrossRefGoogle Scholar
  18. Lin P, Chen F, Sun J, Zhou J, Wang X, Wang N (2015) Mycotoxin zearalenone induces apoptosis in mouse Leydig cells via an endoplasmic reticulum stress-dependent signalling pathway. Reprod Toxicol 52:71–77CrossRefGoogle Scholar
  19. Ling XM, Zhang XH, Tan Y, Yang JJ, Ji B, Wu XR (2017) Protective effects of oviductus ranae on oxidative stress-induced apoptosis in rat ovarian granulosa cells. J Ethnopharmacol pii S0378-8741(16):31984–31985Google Scholar
  20. Long M, Liu Y, Cao Y, Wang N, Dang M, He J (2016) Proanthocyanidins attenuation of chronic lead-induced liver oxidative damage in Kunming mice via the Nrf2/ARE pathway. Nutrients. 8(10). Pii: E656Google Scholar
  21. Long M, Yang S, Zhang Y, Li P, Han J, Dong S (2017) Proanthocyanidin protects against acute zearalenone-induced testicular oxidative damage in male mice. Environ Sci Pollut Res 24(1):938–946CrossRefGoogle Scholar
  22. Lu MC, Ji JA, Jiang ZY, You QD (2016) The Keap1-Nrf2-ARE pathway as a potential preventive and therapeutic target: an update. Med Res Rev 36(5):924–963CrossRefGoogle Scholar
  23. Luan S, Yun X, Rao W, Xiao C, Xu Z, Lang J (2017) Emamectin benzoate induces ROS-mediated DNA damage and apoptosis in Trichoplusia Tn5B1-4 cells. Chem Biol Interact 273:90–98CrossRefGoogle Scholar
  24. Luo Y, Yoshizawa T, Katayama T (1990) Comparative study on the natural occurrence of Fusarium mycotoxins (trichothecenes and zearalenone) in corn and wheat from high- and low-risk areas for human esophageal cancer in China. Appl Environ Microbiol 56(12):3723–3726Google Scholar
  25. Naaz F, Abdin MZ, Javed S (2014) Protective effect of esculin against prooxidant aflatoxin B1-induced nephrotoxicity in mice. Mycotoxin Res. 30(1):25–32CrossRefGoogle Scholar
  26. Park IJ, Cha SY, Kang M, So YS, Go HG, Mun SP (2011) Effect of proanthocyanidin-rich extract from Pinus radiata bark on immune response of specific-pathogen-free White Leghorn chickens. Poult Sci 90(5):977–982CrossRefGoogle Scholar
  27. Park JC, Lee SH, Hong JK, Cho JH, Kim I.H., Park SK (2014) Effect of dietary supplementation of procyanidin on growth performance and immune response in pigs.Asian-Australas J Anim Sci 27(1):131–139Google Scholar
  28. Schoevers EJ, Santos RR, Colenbrander B, Fink-Gremmels J, Roelen BA (2012) Transgenerational toxicity of zearalenone in pigs. Reprod Toxicol 34(1):110–119CrossRefGoogle Scholar
  29. Schwartz P, Thorpe KL, Bucheli TD, Wettstein FE, Burkhardt-Holm P (2010) Short-term exposure to the environmentally relevant estrogenic mycotoxin zearalenone impairs reproduction in fish. Sci Total Environ 409(2):326–333CrossRefGoogle Scholar
  30. Shao ZH, Hsu CW, Chang WT, Waypa GB, Li J, Li D (2006) Cytotoxicity induced by grape seed proanthocyanidins: role of nitric oxide. Cell Biol Toxicol 22(3):149–158CrossRefGoogle Scholar
  31. Sies H, Berndt C, Jones DP (2017) Oxidative stress. Annu Rev Biochem 86:715–748Google Scholar
  32. Tatay E, Espín S, García-Fernández AJ, Ruiz M J (2017) Oxidative damage and disturbance of antioxidant capacity by zearalenone and its metabolites in human cells. Toxicol in vitro. Pii: S0887-2333(17)30111-XGoogle Scholar
  33. Tatay E, Font G, Ruiz MJ (2016) Cytotoxic effects of zearalenone and its metabolites and antioxidant cell defense in CHO-K1 cells. Food Chem Toxicol 96:43–49CrossRefGoogle Scholar
  34. Tiemann U, Viergutz T, Jonas L, Schneider F (2003) Influence of the myeotoxins alpha-and beta-zearalenol and dexoxynivalenonol on the cell of cycle of cutuled porcine endometrial cell. ReProd Toxiol 174(2):209–218CrossRefGoogle Scholar
  35. Van Le Thanh B, Lemay M, Bastien A, Lapointe J, Lessard M, Chorfi Y (2016) The potential effects of antioxidant feed additives in mitigating the adverse effects of corn naturally contaminated with Fusarium mycotoxins on antioxidant systems in the intestinal mucosa, plasma, and liver in weaned pigs. Mycotoxin Res 32(2):99–116CrossRefGoogle Scholar
  36. Wang ML, Suo X, Gu JH, Zhang WW, Fang Q, Wang X (2008) Influence of grape seed proanthocyanidin extract in broiler chickens: effect on chicken coccidiosis and antioxidant status. Poult Sci 87(11):2273–2280CrossRefGoogle Scholar
  37. Xu ML, Hu J, Guo BP, Niu YR, Xiao C, Xu YX (2016) Exploration of intrinsic and extrinsic apoptotic pathways in zearalenone-treated rat Sertoli cells. Environ Toxicol 31(12):1731–1739CrossRefGoogle Scholar
  38. Xu W, Li F, Xu Z, Sun B, Cao J, Liu Y (2017) Tert-butylhydroquinone protects PC12 cells against ferrous sulfateinduced oxidative and inflammatory injury via the Nrf2/ARE pathway. Chem Biol Interact 273:28–36CrossRefGoogle Scholar
  39. Yu M, Chen L, Peng Z, Wang D, Song Y, Wang H (2017) Embryotoxicity caused by DON-induced oxidative stress mediated by Nrf2/HO-1 pathway. Toxins (Basel). 9(6). Pii: E188.  https://doi.org/10.3390/toxins9060188
  40. Zhang GL, Sun XF, Feng YZ, Li B, Li YP, Yang F (2017) Zearalenone exposure impairs ovarian primordial follicle formation via down-regulation of Lhx8 expression in vitro. Toxicol Appl Pharmacol 317:33–40CrossRefGoogle Scholar
  41. Zhang Z, Zheng L, Zhao Z, Shi J, Wang X, Huang J (2014) Grape seed proanthocyanidins inhibit H2O2-induced osteoblastic MC3T3-E1 cell apoptosis via ameliorating H2O2-induced mitochondrial dysfunction. J Toxicol Sci 39(5):803–813CrossRefGoogle Scholar
  42. Zinedine A, Soriano JM, MoltóJ C, Mañes J (2007) Review on the toxicity, occurrence, metabolism, detoxification, regulations and intake of zearalenone: an oestrogenic mycotoxin. Food Chem Toxicol 45:1–1CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Miao Long
    • 1
  • Shu-Hua Yang
    • 1
  • Wei Shi
    • 1
  • Peng Li
    • 1
  • Yang Guo
    • 1
  • Jiayi Guo
    • 1
  • Jian-Bin He
    • 1
  • Yi Zhang
    • 1
    Email author
  1. 1.College of Animal Science and Veterinary MedicineShenyang Agricultural UniversityShenyangChina

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