Department of Pharmaceutical and Biomedical Sciences, School of Pharmacy, University of Salerno, via Ponte Don Melillo, 11/c Fisciano (SA), Italy.
Toxicon. 2012 May;59(6):644-50. doi: 10.1016/j.toxicon.2012.02.010. Epub 2012 Mar 3.
Aflatoxins are natural contaminants frequently found both in food and feed. Many of them exert immunomodulatory properties in mammals; therefore, the aim of the current study was to investigate immune-effects of AFB1, AFB2, AFM1 and AFM2, alone and differently combined, in J774A.1 murine macrophages. MTT assay showed that AFB1, alone and combined with AFB2, possess antiproliferative activity only at the highest concentration; such effect was not shown by their hydroxylated metabolites, AFM1 and AFM2, respectively. However, the immunotoxic effects of the aflatoxins evaluated in the current study may be due to the inhibition of production of active oxygen metabolites such as NO. Cytofluorimetric assay in macrophages exposed to aflatoxins (10-100 μM) revealed that their cytoxicity is not related to apoptotic pathways. Nevertheless, a significant increase of the S phase cell population accompanied by a decrease in G0/G1 phase cell population was observed after AFB1 treatment. In conclusion, the results of the current study suggest that aflatoxins could compromise the macrophages functions; in particular, co-exposure to AFB1, AFB2, AFM1 and AFM2 may exert interactions which can significantly affect immunoreactivity.
黄曲霉毒素是一种常见的食品和饲料污染物。它们中的许多物质在哺乳动物中具有免疫调节特性；因此，本研究旨在研究 AFB1、AFB2、AFM1 和 AFM2 单独及不同组合对 J774A.1 巨噬细胞的免疫效应。MTT 检测表明，AFB1 及其与 AFB2 的组合仅在最高浓度下具有抗增殖活性；其羟基代谢物 AFM1 和 AFM2 则没有表现出这种作用。然而，本研究评估的黄曲霉毒素的免疫毒性作用可能是由于抑制了活性氧代谢物（如 NO）的产生。细胞荧光检测显示，在接触黄曲霉毒素（10-100 μM）的巨噬细胞中，其细胞毒性与凋亡途径无关。然而，在用 AFB1 处理后，观察到 S 期细胞群体显著增加，同时 G0/G1 期细胞群体减少。总之，本研究结果表明，黄曲霉毒素可能会损害巨噬细胞的功能；特别是，AFB1、AFB2、AFM1 和 AFM2 的共同暴露可能会产生相互作用，从而显著影响免疫反应性。
