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首页> 外文期刊>Journal of Agricultural and Food Chemistry >Effect of Dioxins in Milk on the 3D Cultured Primary Buffalo Hepatocyte Model System
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Effect of Dioxins in Milk on the 3D Cultured Primary Buffalo Hepatocyte Model System

机译：二恶英在牛奶中对3D培养的原发性水牛肝细胞模型系统的影响

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Cow and human milk have been reported to contain dioxins ranging from 0.023 to 26.46 and 0.88 to 19 pg/g of fat, respectively. However, the toxic effects of the dioxins in the milk in this range of concentrations were not explored. Therefore, considering the outbred livestock tissues as better models than inbred laboratory animals, the present study targeted to study the effect of dioxins present in the milk on three-dimensionally (3D) cultured buffalo primary hepatocyte spheroids. The spheroids were treated with a model dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), directly and also through milk fat at different concentrations (i.e, 0.02-20 pg/mL) for 24 h. Among the liver-cell-specific (ALB, HNF4 alpha, and AFP) genes, a similar ALB and upregulated HNF4 alpha expression at all treatments indicated the functional and transcriptionally active hepatocyte spheroids. Supportingly, no significant difference in the antiapoptotic gene expression between the treatments of milk fat and milk fat containing dioxins indicated the survivability of the spheroids during dioxin treatments. Among the selected TCDD responsive (CYP1A1, CYP1A2, AHR, CYP1B1, and TIPARP) genes, a nonsignificant increasing trend of the CYP1A1 expression was observed from 0.2 to 10 pg/mL of TCDD concentration through milk fat. This pattern was similar to the reported insensitive response of human primary hepatocytes toward dioxins than that of rat primary hepatocytes. This may indicate that the buffalo hepatocyte spheroids could be better models than rats for TCDD hepatotoxic studies. Further, TCDD in the milk in the range of 0.02-20 pg/mL concentration may not be very hepatotoxic.
机译：据报道，牛和人乳含有分别为0.023至26.46和0.88至19 pg / g脂肪的二恶英。然而，未探索二恶英在这种浓度范围内牛奶中的二恶英的毒性作用。因此，考虑到剩余的牲畜组织作为更好的模型，而不是近铬实验动物，本研究旨在研究三维（3D）培养的水牛原发性肝细胞球体的二恶英存在于乳中的二恶英。将球状体用模型二恶英，2,3,7,8-四氯二氯胺-P-二恶蛋白（TCDD），并通过不同浓度（即0.02-20pg / ml）的乳脂处理24小时。在肝细胞特异性（ALB，HNF4α和AFP）基因中，在所有处理中类似的ALB和上调的HNF4α表达表明功能性和转录活性肝细胞球体。携带类乳脂和牛奶脂肪的处理与含二恶英的治疗之间的抗透露基因表达没有显着差异表明了二恶英处理期间的球状体的活力。在所选择的TCDD响应（CYP1A1，CYP1A2，AHR，CYP1B1和TIPARP）基因中，通过乳脂肪从0.2至10pg / ml的TCDD浓度观察到CYP1A1表达的不显着增加的趋势。这种模式类似于报告的人原发性肝细胞对二恶英的不敏感反应而不是大鼠原发性肝细胞。这可能表明，水牛肝细胞球体可能比TCDD肝毒性研究的大鼠更好。此外，牛奶中的TCDD在0.02-20pg / ml浓度范围内可能不是非常肝毒性的。

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