title: Analysis of individual and combined effects of ochratoxin A and zearalenone on HepG2 and KK-1 cells with mathematical models.
abstract: Ochratoxin A (OTA) and Zearalenone (ZEA) are widespread mycotoxins that contaminate foodstuffs simultaneously, but sufficient data regarding their mixed toxicities are lacking. This study aims to analyze the style of combined effects of OTA and ZEA on cells of their target organs. For this purpose, cytotoxicity was determined in HepG2 and KK-1 cells treated with single and combined forms of OTA and ZEA. Furthermore, we have analyzed the data using two mathematical models based on the concepts of concentration addition (CA) and independent addition (IA). By analyzing data with nonlinear regression, toxins applied singly showed classic sigmoid dose-response curves in HepG2 cells whereas in KK-1 cells hormetic responses were observed. Exposure to equieffective mixtures of OTA and ZEA showed additive effects, irrespective of different nonlinear regression models used. Our results demonstrate that IA is an appropriate concept to account for mixture effects of OTA and ZEA. The results in ROS generation indicate a departure from additivity to antagonism or synergism at different concentrations, probably due to potential interaction during ROS production. This study shows that a risk assessment of mycotoxins should account for mixture effects, and prediction models are valuable tools for mixture assessment.
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. liyuzhe611@163.com.
authors.forename: Yuzhe
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. boyang0214@126.com.
authors.forename: Boyang
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. raininghe@163.com.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Food Science, Nutrition and Health Promotion, Mississippi State University, Mississippi State, MS 39762, USA. wcheng@fsnhp.msstate.edu.
authors.forename: Wen-Hsing
authors.initials: WH
authors.lastname: Cheng
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. xuwentaoboy@sina.com.
authors.forename: Wentao
authors.initials: W
authors.lastname: Xu
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. liyuzhe611@163.com.
authors.forename: Yunbo
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. renee.lr@qq.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Liang
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. luohaoshu@cau.edu.cn.
authors.forename: Haoshu
authors.initials: H
authors.lastname: Luo
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
authors.forename: Kunlun
authors.initials: K
authors.lastname: Huang
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D017711:Nonlinear Dynamics; D009793:Ochratoxins / Q000633:toxicity*; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D018570:Risk Assessment; D015025:Zearalenone / Q000633:toxicity*
chemical_list: D009793:Ochratoxins; D017382:Reactive Oxygen Species; C025589:ochratoxin A; D015025:Zearalenone