title: Individual and combined cytotoxic effects of aflatoxin B1, zearalenone, deoxynivalenol and fumonisin B1 on BRL 3A rat liver cells.
abstract: This study was performed to determine the individual and combined cytotoxic effects of Aflatoxin B1 (AFB1), zearalenone (ZEA), deoxynivalenol (DON) and fumonisin B1 (FB1) on BRL 3A rat liver cells. After the mycotoxins treated the BRL 3A cells for 12, 24 and 48 h, cell viability was determined using the MTT assay. The cytotoxicity of individual mycotoxins on BRL 3A cell viability in decreasing order were DON > AFB1 > ZEA > FB1. The central composite design (CCD) was used to assess the toxicity of binary and ternary mixtures of these mycotoxins. The mixtures of AFB1+ZEA and AFB1+DON showed the synergetic toxic effects on BRL 3A cells. These toxins decreased the viability of cells by inducing intracellular reactive oxygen species (ROS) production and promoting apoptosis in the BRL 3A cells. This effect was mediated by an upregulation of the stress and apoptotic genes Hsp70, p53, Bax, Caspase-3 and Caspase-8, along with a downregulation of the antiapoptotic gene Bcl-2. In conclusion, our results suggested that the coexistence of AFB1 and ZEA or DON in agricultural products could be more hepatotoxic than individually, suggests that the toxicological interactions of these toxins need to be better understood to assess health risks.
authors.affiliation: Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Lv-Hui
authors.initials: LH
authors.lastname: Sun
authors.affiliation: Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Ming-Yan
authors.initials: MY
authors.lastname: Lei
authors.affiliation: Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Ni-Ya
authors.initials: NY
authors.lastname: Zhang
authors.affiliation: Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Animal Science, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Christopher Steven
authors.initials: CS
authors.lastname: Krumm
authors.affiliation: Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China. Electronic address: qds@mail.hzau.edu.cn.
authors.forename: De-Sheng
authors.initials: DS
authors.lastname: Qi
mesh_terms: D016604:Aflatoxin B1 / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D037341:Fumonisins / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014255:Trichothecenes / Q000633:toxicity*; D015025:Zearalenone / Q000633:toxicity*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D037341:Fumonisins; D017382:Reactive Oxygen Species; D014255:Trichothecenes; D051028:bcl-2-Associated X Protein; C056933:fumonisin B1; D015025:Zearalenone; D016604:Aflatoxin B1; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; D053148:Caspase 3; D053181:Caspase 8; C007262:deoxynivalenol
keywords: Aflatoxin B(1); BRL 3A rat liver cells; Cytotoxicity; Deoxynivalenol; Fumonisin B(1); Zearalenone