The combination of T-2 toxin and acrylamide synergistically induces hepatotoxicity and nephrotoxicity via the activation of oxidative stress and the mitochondrial pathway
The combination of T-2 toxin and acrylamide synergistically induces hepatotoxicity and nephrotoxicity via the activation of oxidative stress and the mitochondrial pathway
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DOI：
10.1016/j.toxicon.2020.11.007
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发表时间：
2021-01-15
期刊：
影响因子：
2.8
通讯作者：
Yin, Shutao
中科院分区：
文献类型：
--
作者：
Hou, Lirui;Liu, Shuo;Yin, Shutao
T - 2毒素是一种常见的真菌毒素，不仅广泛存在于小麦、大麦、玉米等粮食作物及其相关产品中，也存在于各种动物饲料中。丙烯酰胺（ACR）主要由游离氨基酸天冬酰胺和还原糖（如葡萄糖和果糖）形成，常见于薯片、薯条、烤面包、咖啡等食品中。因此，人们很可能通过日常饮食摄入同时被T - 2毒素和ACR污染的食物。由于肝脏和肾脏可能是T - 2毒素和ACR的毒性作用靶点，本研究利用细胞培养和动物模型评估联合暴露是否会增加肝毒性和肾毒性。我们使用L02和MARC - 145细胞，分别用T - 2毒素（5 - 15 nM）和ACR（1 - 3 mM）单独处理，或按照1 : 200（T - 2毒素/ACR）的固定比例联合处理。使用ACR（50 mg/kg，灌胃，5天）和T - 2毒素（5 mg/kg，灌胃，5天）来评估C57BL/6N小鼠的生化、蛋白质和组织学变化。结果显示，联合处理在体外导致协同细胞毒性，同时在体内显著增加肝脏和肾脏毒性。从机制上讲，T - 2毒素降低了锰超氧化物歧化酶的表达，而ACR降低了过氧化氢酶的表达。这两种机制在联合作用时相互汇聚，导致氧化应激产生增强。这些研究结果强调了在对这些食源污染物进行安全性评估时考虑联合毒性的必要性。
T-2 toxin is a common fungal toxin, which is not only widely found in wheat, barley, corn, and other food crops and their related products, but also in various animal feeds. Acrylamide (ACR) is mainly formed by the free amino acid, asparagine and reducing sugars, such as glucose and fructose, and is commonly found in potato chips, French fries, toast, coffee, and other foods. Therefore, people are highly likely to consume food via their daily diets that are contaminated with both T-2 toxin and ACR. Since liver and kidneys were possible toxic targets of both T-2 toxin and ACR, this study assessed whether combined exposure could increase hepatotoxicity and nephrotoxicity using both cell cultures and animal models. We used L02 and MARC-145 cells and treated with T-2 toxin (5-15 nM) and ACR (1-3 mM) alone or in combination with a fixed ratio of 1:200 (T-2 toxin/ACR). ACR (50 mg/kg, i.g., 5d) and T-2 toxin (5 mg/kg, i.g., 5d) were used to assess the biochemical, proteins and histplogical changes in C57BL/6N mice. Results showed the combination resulted in synergistic cytotoxicity in vitro, while significantly increasing liver and kidney toxicity in vivo. Mechanistically, T-2 toxin decreased Manganese superoxide dismutase expression, while ACR reduced catalase expression. These two mechanisms were converged in response to the combination, leading to enhanced oxidative stress generation. The findings highlighted the necessity to consider the combined toxicity during the safety assessment of these food-borne contaminants.