802
Views
17
CrossRef citations to date
0
Altmetric
Articles

Mechanisms of cell death induction by food-borne mycotoxins

, , &

References

  • Abbès, S., Ben Salah-Abbès, J., Jebali, R., Younes, R. B. and Oueslati, R. (2016). Interaction of aflatoxin B1 and fumonisin B1 in mice causes immunotoxicity and oxidative stress: possible protective role using lactic acid bacteria. J. Immunotoxicol. 13:46–54.
  • Abdel-Wahhab, M. A., Salman, A. S., Ibrahim, M. I., El-Kady, A. A., Abdel-Aziem, S. H., Hassan, N. S. and Waly, A. I. (2016). Curcumin nanoparticles loaded hydrogels protects against aflatoxin B1-induced genotoxicity in rat liver. Food Chem. Toxicol. 94:159–171.
  • Agrawal, M., Bhaskar, A. S. and Lakshmana Rao, P. V. (2015). Involvement of mitogen-activated protein kinase pathway in T-2 toxin-induced cell cycle alteration and apoptosis in human neuroblastoma cells. Mol. Neurobiol. 51:1379–1394.
  • Aguileta, M. A., Rojas-Rivera, D., Goossens, V., Estornes, Y., Van Isterdael, G., Vandenabeele, P. and Bertrand, M. J. (2016). A siRNA screen reveals the prosurvival effect of protein kinase A activation in conditions of unresolved endoplasmic reticulum stress. Cell Death Differ. 23:1670–1680.
  • Alizadeh, A. M., Mohammadghasemi, F., Zendehdel, K., Kamyabi-Moghaddam, Z., Tavassoli, A., Amini-Najafi, F. and Khosravi, A. (2015). Apoptotic and proliferative activity of mouse gastric mucosa following oral administration of fumonisin B1. Iran J. Basic Med. Sci. 18:8–13.
  • Assaf, H., Azouri, H. and Pallardy, M. (2004). Ochratoxin A induces apoptosis in human lymphocytes through down regulation of Bcl-xL. Toxicol Sci. 79:335–344.
  • Ayed-Boussema, I., Bouaziz, C., Rjiba, K., Valenti, K., Laporte, F., Bacha, H. and Hassen, W. (2008). The mycotoxin Zearalenone induces apoptosis in human hepatocytes (HepG2) via p53-dependent mitochondrial signaling pathway. Toxicol In Vitro. 22:1671–1680.
  • Banjerdpongchai, R., Kongtawelert, P., Khantamat, O., Srisomsap, C., Chokchaichamnankit, D., Subhasitanont, P. and Svasti, J. (2010). Mitochondrial and endoplasmic reticulum stress pathways cooperate in zearalenone-induced apoptosis of human leukemic cells. J. Hematol Oncol. 3:1–16.
  • Ben Salem, I., Prola, A., Boussabbeh, M., Guilbert, A., Bacha, H., Abid-Essefi, S. and Lemaire, C. (2015). Crocin and quercetin protect HCT116 and HEK293 cells from Zearalenone-induced apoptosis by reducing endoplasmic reticulum stress. Cell Stress Chaperones. 20:927–938.
  • Bennett, J. W. and Klich, M. (2003). Mycotoxins. Clin Microbiol Rev. 16:497–516.
  • Bouaziz, C., Sharaf el dein, O., Martel, C., El Golli, E., Abid-Essefi, S., Brenner, C., Lemaire, C. and Bacha, H. (2011). Molecular events involved in ochratoxin A induced mitochondrial pathway of apoptosis, modulation by Bcl-2 family members. Environ. Toxicol. 26:579–590.
  • Boussabbeh, M., Ben Salem, I., Belguesmi, F., Neffati, F., Najjar, M. F., Abid-Essefi, S. and Bacha, H. (2016a). Crocin protects the liver and kidney from patulin-induced apoptosis in vivo. Environ. Sci. Pollut Res. Int. 23:9799–9808.
  • Boussabbeh, M., Ben Salem, I., Prola, A., Guilbert, A., Bacha, H., Abid-Essefi, S. and Lemaire, C. (2015). Patulin induces apoptosis through ROS-mediated endoplasmic reticulum stress pathway. Toxicol Sci. 144:328–337.
  • Boussabbeh, M., Ben Salem, I., Rjiba-Touati, K., Bouyahya, C., Neffati, F., Najjar, M. F., Bacha, H. and Abid-Essefi, S. (2016b). The potential effect of patulin on mice bearing melanoma cells: an anti-tumour or carcinogenic effect? Tumour Biol. 37:6285–6295.
  • Cagnol, S. and Chambard, J. C. (2010). ERK and cell death: mechanisms of ERK-induced cell death–apoptosis, autophagy and senescence. FEBS J. 277:2–21.
  • Cariddi, L. N., Escobar, F. M., Sabini, M. C., Campra, N. A., Bagnis, G., Decote-Ricardo, D., Freire-de-Lima, C. G., Mañas, F., Sabini, L. I. and Dalcero, A. M. (2016). Phenolic acid protects of renal damage induced by ochratoxin A in a 28-days-oral treatment in rats. Environ. Toxicol Pharmacol. 43:105–111.
  • Chang, C. H., Yu, F. Y., Wang, L. T., Lin, Y. S. and Liu, B. H. (2009). Activation of ERK and JNK signaling pathways by mycotoxin citrinin in human cells. Toxicol Appl. Pharmacol. 237:281–287.
  • Chang, C. H., Yu, F. Y., Wu, T. S., Wang, L. T. and Liu, B. H. (2011). Mycotoxin citrinin induced cell cycle G2/M arrest and numerical chromosomal aberration associated with disruption of microtubule formation in human cells. Toxicol Sci. 119:84–92.
  • Chang, H. T., Chou, C. T., Chen, I. S., Yu, C. C., Lu, T., Hsu, S. S., Shieh, P., Jan, C. R. and Liang, W. Z. (2016). Mechanisms underlying effect of the mycotoxin cytochalasin B on induction of cytotoxicity, modulation of cell cycle, Ca2+ homeostasis and ROS production in human breast cells. Toxicology. 370:1–19.
  • Chen, C. C. and Chan, W. H. (2009). Inhibition of citrinin-induced apoptotic biochemical signaling in human hepatoma G2 cells by resveratrol. Int. J. Mol. Sci. 10:3338–3357.
  • Chen, F., Li, Q., Zhang, Z., Lin, P., Lei, L., Wang, A. and Jin, Y. (2015). Endoplasmic reticulum stress cooperates in zearalenone-induced cell death of RAW 264.7 macrophages. Int. J. Mol. Sci. 16:19780–19795.
  • Chen, Y. R. and Tan, T. H. (1998). Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway by curcumin. Oncogene. 17:173–178.
  • Chopra, M., Link, P., Michels, C. and Schrenk, D. (2010). Characterization of ochratoxin A-induced apoptosis in primary rat hepatocytes. Cell Biol. Toxicol. 26:239–254.
  • Corcuera, L. A., Vettorazzi, A., Arbillaga, L., Pérez, N., Gil, A. G., Azqueta, A., González-Peñas, E., García-Jalón, J. A. and López de Cerain, A. (2015). Genotoxicity of aflatoxin B1 and ochratoxin A after simultaneous application of the in vivo micronucleus and comet assay. Food Chem. Toxicol. 76:116–124.
  • Cui, J., Liu, J., Wu, S., Wang, Y., Shen, H., Xing, L., Wang, J., Yan, X. and Zhang, X. (2013). Oxidative DNA damage is involved in ochratoxin A-induced G2 arrest through ataxia telangiectasia-mutated (ATM) pathways in human gastric epithelium GES-1 cells in vitro. Arch. Toxicol. 87:1829–1840.
  • Dai, Q., Zhao, J., Qi, X., Xu, W., He, X., Guo, M., Dweep, H., Cheng, W. H., Luo, Y., Xia, K., Gretz, N. and Huang, K. (2014). MicroRNA profiling of rats with ochratoxin A nephrotoxicity. BMC Genomics. 15:333.
  • Darif, Y., Mountassif, D., Belkebir, A., Zaid, Y., Basu, K., Mourad, W. and Oudghiri, M. (2016). Ochratoxin A mediates MAPK activation, modulates IL-2 and TNF-α mRNA expression and induces apoptosis by mitochondria-dependent and mitochondria-independent pathways in human H9 T cells. J. Toxicol Sci. 41:403–416.
  • De Ruyck, K., De Boevre, M., Huybrechts, I. and De Saeger, S. (2015). Dietary mycotoxins, co-exposure, and carcinogenesis in humans: Short review. Mutat Res. Rev. Mutat Res. 766:32–41.
  • Deng, C., Ji, C., Qin, W., Cao, X., Zhong, J., Li, Y., Srinivas, S., Feng, Y. and Deng, X. (2016). Deoxynivalenol inhibits proliferation and induces apoptosis in human umbilical vein endothelial cells. Environ. Toxicol Pharmacol. 43:232–241.
  • Doi, K. and Uetsuka, K. (2011). Mechanisms of mycotoxin-induced neurotoxicity through oxidative stress-associated pathways. Int. J. Mol. Sci. 12:5213–5237.
  • Eletto, D., Chevet, E., Argon, Y. and Appenzeller-Herzog, C. (2014). Redox controls UPR to control redox. J. Cell Sci. 127:3649–3658.
  • El-Nekeety, A. A., El-Kholy, W., Abbas, N. F., Ebaid, A., Amra, H. A. and Abdel-Wahhab, M. A. (2007). Efficacy of royal jelly against the oxidative stress of fumonisin in rats. Toxicon. 50:256–269.
  • Fang, H., Wu, Y., Guo, J., Rong, J., Ma, L., Zhao, Z., Zuo, D. and Peng, S. (2012). T-2 toxin induces apoptosis in differentiated murine embryonic stem cells through reactive oxygen species-mediated mitochondrial pathway. Apoptosis. 17:895–907.
  • Fliege, R. and Metzler, M. (2000). Electrophilic properties of patulin. N-acetylcysteine and glutathione adducts. Chem. Res. Toxicol. 13:373–381.
  • Green, D. R. and Kroemer, G. (2009). Cytoplasmic functions of the tumour suppressor p53. Nature. 458:1127–1130.
  • Guo, X., Dong, Y., Yin, S., Zhao, C., Huo, Y., Fan, L. and Hu, H. (2013). Patulin induces pro-survival functions via autophagy inhibition and p62 accumulation. Cell Death Dis. 4:e822.
  • Han, J., Wang, Q. C., Zhu, C. C., Liu, J., Zhang, Y., Cui, X. S., Kim, N. H. and Sun, S. C. (2016). Deoxynivalenol exposure induces autophagy/apoptosis and epigenetic modification changes during porcine oocyte maturation. Toxicol Appl. Pharmacol. 300:70–76.
  • Hao, S., Pan, S., Hu, J., Qian, G., Gan, F. and Huang, K. (2015). Aflatoxin B1 suppressed T-cell response to anti-pig-CD3 monoclonal antibody stimulation in primary porcine splenocytes: a role for the extracellular regulated protein kinase (ERK1/2) MAPK signaling pathway. J. Agric. Food Chem. 63:6094–6101.
  • He, K., Zhou, H. R. and Pestka, J. J. (2012a). Mechanisms for ribotoxin-induced ribosomal RNA cleavage. Toxicol Appl. Pharmacol. 265:10–18.
  • He, K., Zhou, H. R. and Pestka, J. J. (2012b). Targets and intracellular signaling mechanisms for deoxynivalenol-induced ribosomal RNA cleavage. Toxicol Sci. 127:382–390.
  • Hitomi, J., Christofferson, D. E., Ng, A., Yao, J., Degterev, A., Xavier, R. J. and Yuan, J. (2008). Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway. Cell. 135:1311–1323.
  • Hou, H., Zhou, R., Li, A., Li, C., Li, Q., Liu, J. and Jiang, B. (2014). Citreoviridin inhibits cell proliferation and enhances apoptosis of human umbilical vein endothelial cells. Environ. Toxicol Pharmacol. 37:828–836.
  • Hu, J., Xu, M., Dai, Y., Ding, X., Xiao, C., Ji, H. and Xu, Y. (2016). Exploration of Bcl-2 family and caspases-dependent apoptotic signaling pathway in Zearalenone-treated mouse endometrial stromal cells. Biochem. Biophys. Res. Commun. 476:553–559.
  • Huang, Y. T., Lai, C. Y., Lou, S. L., Yeh, J. M. and Chan, W. H. (2009). Activation of JNK and PAK2 is essential for citrinin-induced apoptosis in a human osteoblast cell line. Environ. Toxicol. 24:343–356.
  • Ihara, T., Sugamata, M., Sekijima, M., Okumura, H., Yoshino, N. and Ueno, Y. (1997). Apoptotic cellular damage in mice after T-2 toxin-induced acute toxicosis. Nat. Toxins. 5:141–145.
  • Islam, M. R., Roh, Y. S., Kim, J., Lim, C. W. and Kim, B. (2013). Differential immune modulation by deoxynivalenol (vomitoxin) in mice. Toxicol Lett. 221:152–163.
  • Islam, Z., Nagase, M., Yoshizawa, T., Yamauchi, K. and Sakato, N. (1998). T-2 toxin induces thymic apoptosis in vivo in mice. Toxicol Appl. Pharmacol. 148:205–214.
  • Jee, Y., Noh, E. M., Cho, E. S. and Son, H. Y. (2010). Involvement of the Fas and Fas ligand in testicular germ cell apoptosis by zearalenone in rat. J. Vet. Sci. 11:115–119.
  • Jin, H., Yin, S., Song, X., Zhang, E., Fan, L. and Hu, H. (2016). p53 activation contributes to patulin-induced nephrotoxicity via modulation of reactive oxygen species generation. Sci. Rep. 6:24455.
  • Kerr, J. F. (2002). History of the events leading to the formulation of the apoptosis concept. Toxicology. 27:471–474.
  • Kim, D. H., Lee, Y. S., Lee, Y. M., Oh, S., Yun, Y. P. and Yoo, H. S. (2007). Elevation of sphingoid base 1-phosphate as a potential contributor to hepatotoxicity in fumonisin B1-exposed mice. Arch. Pharm Res. 30:962–969.
  • Königs, M., Schwerdt, G., Gekle, M. and Humpf, H. U. (2008). Effects of the mycotoxin deoxynivalenol on human primary hepatocytes. Mol. Nutr. Food Res. 52:830–839.
  • Korn, A. K., Gross, M., Usleber, E., Thom, N., Köhler, K. and Erhardt, G. (2014). Dietary ergot alkaloids as a possible cause of tail necrosis in rabbits. Mycotoxin Res. 30:241–250.
  • Kumagai, S., Sugita-Konishi, Y., Hara-Kudo, Y., Ito, Y., Noguchi, Y., Yamamoto, Y. and Ogura, A. (1998). The fate and acute toxicity of aflatoxin B1 in the mastomys and rat. Toxicon. 36:179–188.
  • Kuroda, K., Hibi, D., Ishii, Y., Yokoo, Y., Takasu, S., Kijima, A., Matsushita, K., Masumura, K., Kodama, Y., Yanai, T., Sakai, H., Nohmi, T., Ogawa, K. and Umemura, T. (2015). Role of p53 in the progression from ochratoxin A-induced DNA damage to gene mutations in the kidneys of mice. Toxicol Sci. 144:65–76.
  • Kwon, O., Soung, N. K., Thimmegowda, N. R., Jeong, S. J., Jang, J. H., Moon, D. O., Chung, J. K., Lee, K. S., Kwon, Y. T., Erikson, R. L., Ahn, J. S. and Kim, B. Y. (2012). Patulin induces colorectal cancer cells apoptosis through EGR-1 dependent ATF3 up-regulation. Cell Signal. 24:943–950.
  • Li, D., Ma, H., Ye, Y., Ji, C., Tang, X., Ouyang, D., Chen, J., Li, Y. and Ma, Y. (2014). Deoxynivalenol induces apoptosis in mouse thymic epithelial cells through mitochondria-mediated pathway. Environ. Toxicol Pharmacol. 38:163–171.
  • Li, J., Yin, S., Dong, Y., Fan, L. and Hu, H. (2011). p53 activation inhibits ochratoxin A-induced apoptosis in monkey and human kidney epithelial cells via suppression of JNK activation. Biochem. Biophys. Res. Commun. 411:458–463.
  • Liang, R., Shen, X. L., Zhang, B., Li, Y., Xu, W., Zhao, C., Luo, Y. and Huang, K. (2015). Apoptosis signal-regulating kinase 1 promotes Ochratoxin A-induced renal cytotoxicity. Sci. Rep. 5:8078.
  • Liao, S., Shi, D., Clemons-Chevis, C. L., Guo, S., Su, R., Qiang, P. and Tang, Z. (2014). Protective role of selenium on aflatoxin b1-induced hepatic dysfunction and apoptosis of liver in ducklings. Biol. Trace Elem. Res. 162:296–301.
  • Lim, C. W., Parker, H. M., Vesonder, R. F. and Haschek, W. M. (1996). Intravenous fumonisin B1 induces cell proliferation and apoptosis in the rat. Nat. Toxins. 4:34–41.
  • Lin, P., Chen, F., Sun, J., Zhou, J., Wang, X., Wang, N., Li, X., Zhang, Z., Wang, A. and Jin, Y. (2015). Mycotoxin zearalenone induces apoptosis in mouse Leydig cells via an endoplasmic reticulum stress-dependent signalling pathway. Reprod. Toxicol. 52:71–77.
  • Ling, K. H., Wan, M. L., El-Nezami, H. and Wang, M. (2016). Protective capacity of resveratrol, a natural polyphenolic compound, against deoxynivalenol-induced intestinal barrier dysfunction and bacterial translocation. Chem Res Toxicol. 29:823–833.
  • Liu, B. H., Wu, T. S., Yu, F. Y. and Su, C. C. (2007). Induction of oxidative stress response by the mycotoxin patulin in mammalian cells. Toxicol Sci. 95:340–347.
  • Liu, B. H., Wu, T. S., Yu, F. Y. and Wang, C. H. (2006). Mycotoxin patulin activates the p38 kinase and JNK signaling pathways in human embryonic kidney cells. Toxicol Sci. 89:423–430.
  • Liu, J., Wang, L., Guo, X., Pang, Q., Wu, S., Wu, C., Xu, P. and Bai, Y. (2014). The role of mitochondria in T-2 toxin-induced human chondrocytes apoptosis. PLoS One. 9:e108394.
  • Liu, Y. and Wang, W. (2016). Aflatoxin B1 impairs mitochondrial functions, activates ROS generation, induces apoptosis and involves Nrf2 signal pathway in primary broiler hepatocytes. Anim. Sci. doi: 10.1111/asj.12550.
  • Liu, Y. N., Wang, Y. X., Liu, X. F., Jiang, L. P., Yang, G., Sun, X. C., Geng, C. Y., Li, Q. J., Chen, M. and Yao, X. F. (2015). Citreoviridin induces ROS-dependent autophagic cell death in human liver HepG2 cells. Toxicon. 95:30–37.
  • Long, M., Yang, S. H., Han, J. X., Li, P., Zhang, Y., Dong, S., Chen, X., Guo, J., Wang, J. and He, J. B. (2016). The protective effect of grape-seed proanthocyanidin extract on oxidative damage induced by zearalenone in kunming mice liver. Int. J. Mol. Sci. 17:pii: E808.
  • Lu, J., Yu, J. Y., Lim, S. S., Son, Y. O., Kim, D. H., Lee, S. A., Shi, X. and Lee, J. C. (2013). Cellular mechanisms of the cytotoxic effects of the zearalenone metabolites α-zearalenol and β-zearalenol on RAW264.7 macrophages. Toxicol In Vitro. 27(3):1007–1017.
  • Maillet, A. and Pervaiz, S. (2012). Redox regulation of p53, redox effectors regulated by p53: a subtle balance. Antioxid Redox Signal. 16:1285–1294.
  • Mary, V. S., Theumer, M. G., Arias, S. L. and Rubinstein, H. R. (2012). Reactive oxygen species sources and biomolecular oxidative damage induced by aflatoxin B1 and fumonisin B1 in rat spleen mononuclear cells. Toxicology. 302:299–307.
  • Meki, A. R., Abdel-Ghaffar, S. K. and El-Gibaly, I. (2001). Aflatoxin B1 induces apoptosis in rat liver: protective effect of melatonin. Neuro Endocrinol Lett. 22:417–426.
  • Mulac, D. and Humpf, H. U. (2011). Cytotoxicity and accumulation of ergot alkaloids in human primary cells. Toxicology. 282:112–121.
  • Mulder, J. E., Bondy, G. S., Mehta, R. and Massey, T. E. (2015). The impact of chronic Aflatoxin B1 exposure and p53 genotype on base excision repair in mouse lung and liver. Mutat Res. 773:63–68.
  • Naaz, F., Abdin, M. Z. and Javed, S. (2014). Protective effect of esculin against prooxidant aflatoxin B1-induced nephrotoxicity in mice. Mycotoxin Res. 30:25–32.
  • Osuchowski, M. F. and Sharma, R. P. (2005). Fumonisin B1 induces necrotic cell death in BV-2 cells and murine cultured astrocytes and is antiproliferative in BV-2 cells while N2A cells and primary cortical neurons are resistant. Neurotoxicology. 26:981–992.
  • Özcan, Z., Gül, G. and Yaman, I. (2015). Ochratoxin A activates opposing c-MET/PI3K/Akt and MAPK/ERK 1-2 pathways in human proximal tubule HK-2 cells. Arch. Toxicol. 89:1313–1327.
  • Patil, R. D., Dwivedi, P. and Sharma, A. K. (2006). Critical period and minimum single oral dose of ochratoxin A for inducing developmental toxicity in pregnant Wistar rats. Reprod Toxicol. 22:679–687.
  • Paul, S., Jakhar, R., Bhardwaj, M. and Kang, S. C. (2015). Glutathione-S-transferase omega 1 (GSTO1-1) acts as mediator of signaling pathways involved inaflatoxin B1-induced apoptosis-autophagy crosstalk in macrophages. Free Radic Biol. Me. 89:1218–1230.
  • Peng, X., Chen, K., Chen, J., Fang, J., Cui, H., Zuo, Z., Deng, J., Chen, Z., Geng, Y. and Lai, W. (2015). Aflatoxin B1 affects apoptosis and expression of Bax, Bcl-2, and Caspase-3 in thymus and bursa of fabricius in broiler chickens. Environ. Toxicol. 31:1113–1120.
  • Peng, X., Yu, Z., Liang, N., Chi, X., Li, X., Jiang, M., Fang, J., Cui, H., Lai, W., Zhou, Y. and Zhou, S. (2016). The mitochondrial and death receptor pathways involved in the thymocytes apoptosis induced by aflatoxin B1. Oncotarget. 7:12222–12234.
  • Peraica, M., B., R., A., L. and Pavlovic, M. (1999). Toxic effects of mycotoxins in humans. Bull. World Health Organ. 77:754–766.
  • Petrik, J., Zanić-Grubisić, T., Barisić, K., Pepeljnjak, S., Radić, B., Ferencić, Z. and Cepelak, I. (2003). Apoptosis and oxidative stress induced by ochratoxin A in rat kidney. Arch. Toxicol. 77:685–693.
  • Ramyaa, P. and Padma, V. V. (2013). Ochratoxin-induced toxicity, oxidative stress and apoptosis ameliorated by quercetin–modulation by Nrf2. Food Chem. Toxicol. 62:205–216.
  • Rumora, L., Domijan, A. M., Grubisić, T. Z., Peraica and M. (2007). Mycotoxin fumonisin B1 alters cellular redox balance and signalling pathways in rat liver and kidney. Toxicology. 242:31–38.
  • Rumora, L., Domijan, A. M., Zanić Grubišić, T. and Segvić Klarić, M. (2014). Differential activation of MAPKs by individual and combined ochratoxin A and citrinin treatments in porcine kidney PK15 cells. Toxicon. 90:174–183.
  • Rumora, L., Kovacić, S., Rozgaj, R., Cepelak, I., Pepeljnjak, S. and Zanić Grubisić, T. (2002). Cytotoxic and genotoxic effects of fumonisin B1 on rabbit kidney RK13 cell line. Arch. Toxicol. 76:55–61.
  • Salem, I. B., Boussabbeh, M., Neffati, F., Najjar, M. F., Abid-Essefi, S. and Bacha, H. (2016). Zearalenone-induced changes in biochemical parameters, oxidative stress and apoptosis in cardiac tissue: protective role of crocin. Hum Exp. Toxicol. 35:623–634.
  • Santos, C. X., Tanaka, L. Y., Wosniak, J. and Laurindo, F. R. (2009). Mechanisms and implications of reactive oxygen species generation during the unfolded protein response: roles of endoplasmic reticulum oxidoreductases, mitochondrial electron transport, and NADPH oxidase. Antioxid Redox Signal. 11:2409–2427.
  • Sauvant, C., Holzinger, H. and Gekle, M. (2005). Proximal tubular toxicity of ochratoxin A is amplified by simultaneous inhibition of the extracellular signal-regulated kinases 1/2. J. Pharmacol. Exp. Ther. 313:234–241.
  • Saxena, N., Ansari, K. M., Kumar, R., Dhawan, A., Dwivedi, P. D. and Das, M. (2009). Patulin causes DNA damage leading to cell cycle arrest and apoptosis through modulation of Bax, p(53) and p(21/WAF1) proteins in skin of mice. Toxicol Appl. Pharmacol. 234:192–201.
  • Sharma, N., Suzuki, H., He, Q. and Sharma, R. P. (2005). Tumor necrosis factor alpha-mediated activation of c-Jun NH(2)-terminal kinase as a mechanism for fumonisin B(1) induced apoptosis in murine primary hepatocytes. J. Biochem. Mol. Toxicol. 19:359–367.
  • Shen, H., Liu, J., Wang, Y., Lian, H., Wang, J., Xing, L., Yan, X., Wang, J. and Zhang, X. (2013). Aflatoxin G1-induced oxidative stress causes DNA damage and triggers apoptosis through MAPK signaling pathway in A549 cells. Food Chem. Toxicol. 62:661–669.
  • Solhaug, A., Torgersen, M. L., Holme, J. A., Lagadic-Gossmann, D. and Eriksen, G. S. (2014). Autophagy and senescence, stress responses induced by the DNA-damaging mycotoxin alternariol. Toxicology. 326:119–129.
  • Song, E., Su, C., Fu, J., Xia, X., Yang, S., Xiao, C., Lu, B., Chen, H., Sun, Z., Wu, S. and Song, Y. (2014). Selenium supplementation shows protective effects against patulin-induced brain damage in mice via increases in GSH-related enzyme activity and expression. Life Sci. 109:37–43.
  • Sozmen, M., Devrim, A. K., Tunca, R., Bayezit, M., Dag, S. and Essiz, D. (2014). Protective effects of silymarin on fumonisin B₁-induced hepatotoxicity in mice. J. Vet. Sci. 15:51–60.
  • Stockmann-Juvala, H., Mikkola, J., Naarala, J., Loikkanen, J., Elovaara, E. and Savolainen, K. (2004). Fumonisin B1-induced toxicity and oxidative damage in U-118MG glioblastoma cells. Toxicology. 202:173–183.
  • Stockmann-Juvala, H., Naarala, J., Loikkanen, J., Vähäkangas, K. and Savolainen, K. (2006). Fumonisin B1-induced apoptosis in neuroblastoma, glioblastoma and hypothalamic cell lines. Toxicology. 225:234–241.
  • Tang, Y., Li, J., Li, F., Hu, C. A., Liao, P., Tan, K., Tan, B., Xiong, X., Liu, G., Li, T. and Yin, Y. (2015). Autophagy protects intestinal epithelial cells against deoxynivalenol toxicity by alleviating oxidative stress via IKK signaling pathway. Free Radic Biol. Med. 89:944–951.
  • Turner, P. C., Flannery, B., Isitt, C., Ali, M. and Pestka, J. (2012). The role of biomarkers in evaluating human health concerns from fungal contaminants in food. Nutr. Res. Rev. 25:162–179.
  • Vlata, Z., Porichis, F., Tzanakakis, G., Tsatsakis, A. and Krambovitis, E. (2006). A study of zearalenone cytotoxicity on human peripheral blood mononuclear cells. Toxicol Lett. 165(3):274–281.
  • Wang, K. and Klionsky, D. J. (2011). Mitochondria removal by autophagy. Autophagy. 7:297–300.
  • Wang, M. and Kaufman, R. J. (2016). Protein misfolding in the endoplasmic reticulum as a conduit to human disease. Nature. 529:326–335.
  • Wang, W., Jones, C., Ciacci-Zanella, J., Holt, T., Gilchrist, D. G. and Dickman, M. B. (1996). Fumonisins and Alternaria alternata lycopersici toxins: sphinganine analog mycotoxins induce apoptosis in monkey kidney cells. Proc. Natl. Acad Sci. U S A. 93:3461–3465.
  • Wang, Y., Liu, J., Cui, J., Xing, L., Wang, J., Yan, X. and Zhang, X. (2012). ERK and p38 MAPK signaling pathways are involved in ochratoxin A-induced G2 phase arrest in human gastric epithelium cells. Toxicol Lett. 209:186–192.
  • Wang, Y., Liu, Y., Liu, X., Jiang, L., Yang, G., Sun, X., Geng, C., Li, Q., Yao, X. and Chen, M. (2015). Citreoviridin induces autophagy-dependent apoptosis through lysosomal-mitochondrial axis in human liver HepG2 cells. Toxins (Basel). 7(8):3030–3044.
  • Wang, Y., Zheng, W., Bian, X., Yuan, Y., Gu, J., Liu, X., Liu, Z. and Bian, J. (2014). Zearalenone induces apoptosis and cytoprotective autophagy in primary Leydig cells. Toxicol Lett. 226:182–191.
  • Wätjen, W., Debbab, A., Hohlfeld, A., Chovolou, Y., Kampkötter, A., Edrada, R. A., Ebel, R., Hakiki, A., Mosaddak, M., Totzke, F., Kubbutat, M. H. and Proksch, P. (2009). Enniatins A1, B and B1 from an endophytic strain of Fusarium tricinctum induce apoptotic cell death in H4IIE hepatoma cells accompanied by inhibition of ERK phosphorylation. Mol. Nutr. Food Res. 53:431–440.
  • Wu, T. S., Liao, Y. C., Yu, F. Y., Chang, C. H. and Liu, B. H. (2008). Mechanism of patulin-induced apoptosis in human leukemia cells (HL-60). Toxicol Lett. 183:105–111.
  • Yang, S. H., Sharrocks, A. D. and Whitmarsh, A. J. (2013). MAP kinase signalling cascades and transcriptional regulation. Gene. 513:1–13.
  • Yin, S., Guo, X., Li, J., Fan, L. and Hu, H. (2016). Fumonisin B1 induces autophagic cell death via activation of ERN1-MAPK8/9/10 pathway in monkey kidney MARC-145 cells. Arch. Toxicol. 90:985–996.
  • Yu, J. Y., Zheng, Z. H., Son, Y. O., Shi, X., Jang, Y. O. and Lee, J. C. (2011). Mycotoxin zearalenone induces AIF- and ROS-mediated cell death through p53- and MAPK-dependent signaling pathways in RAW264.7 macrophages. Toxicol In Vitro. 25:1654–1663.
  • Yuan, S., Wu, B., Yu, Z., Fang, J., Liang, N., Zhou, M., Huang, C. and Peng, X. (2016). The mitochondrial and endoplasmic reticulum pathways involved in the apoptosis of bursa of Fabricius cells in broilers exposed to dietary aflatoxin B1. Oncotarget. 40:65295–65306.
  • Zhang, B., Peng, X., Li, G., Xu, Y., Xia, X. and Wang, Q. (2015). Oxidative stress is involved in Patulin induced apoptosis in HEK293 cells. Toxicon. 94:1–7.
  • Zhang, Z., Yang, X., Wang, Y., Wang, X., Lu, H., Zhang, X., Xiao, X., Li, S., Wang, X. and Wang, S. L. (2013). Cytochrome P450 2A13 is an efficient enzyme in metabolic activation of aflatoxin G1 in human bronchial epithelial cells. Arch. Toxicol. 87:1697–1707.
  • Zhu, C. C., Zhang, Y., Duan, X., Han, J. and Sun, S. C. (2016). Toxic effects of HT-2 toxin on mouse oocytes and its possible mechanisms. Arch. Toxicol. 90:1495–505.
  • Zhu, L., Yuan, H., Guo, C., Lu, Y., Deng, S., Yang, Y., Wei, Q., Wen, L. and He, Z. (2012). Zearalenone induces apoptosis and necrosis in porcine granulosa cells via a caspase-3- and caspase-9-dependent mitochondrial signaling pathway. J. Cell Physiol. 227:1814–1820.
  • Zhuang, Z., Yang, D., Huang, Y. and Wang, S. (2013). Study on the apoptosis mechanism induced by T-2 toxin. PLoS One. 8:e83105.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.