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脱氧雪腐镰刀菌烯醇和黄曲霉毒素 B1 联合作用的无可见不良反应水平在体内和体外诱导免疫抑制和细胞凋亡。

No-observed adverse effect levels of deoxynivalenol and aflatoxin B1 in combination induced immune inhibition and apoptosis in vivo and in vitro.

机构信息

College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China; Institute of Animal Nutritional Health, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China.

College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China; Institute of Animal Nutritional Health, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China.

出版信息

Food Chem Toxicol. 2024 Jul;189:114745. doi: 10.1016/j.fct.2024.114745. Epub 2024 May 17.

DOI:10.1016/j.fct.2024.114745
PMID:38763499
Abstract

Mycotoxins are toxic metabolites produced by fungal species, commonly exist in animal feeds, and pose a serious risk to human as well as animal health. But limited studies have focused on combined effects of no-observed adverse effect levels. In vivo study, 6 weeks old twenty-four mice were individually exposed to Deoxynivalenol (DON) at 0.1 mg/kg BW, Aflatoxin B1 (AFB1) at 0.01 mg/kg BW, and mixture of DON and AFB1 (0.1 mg/kg BW and 0.01 mg/kg BW, respectively) for 28 days. Then, DON at 0.5 μg/mL, AFB1 at 0.04 μg/mL, and mixtures of DON and AFB1 (0.5 μg/mL, 0.04 μg/mL, respectively) were applied to porcine alveolar macrophages (PAMs) in vitro study. Our in vivo results revealed that the combined no-observed adverse effect levels of DON and AFB1 administration decreased IgA and IgG levels in the serum, the splenic TNF-α, IFN-γ, IL-2 and IL-6 mRNA expression and T-lymphocyte subset levels (CD4 and CD8) in the spleen. Additionally, the combined administration increased caspase-3, caspase-9, Bax, Cyt-c, and decreased Bcl-2 protein expression. Taken together, the combined no-observed adverse effect levels of DON and AFB1 could induce immunosuppression, which may be related to apoptosis. This study provides new insights into the combined immune toxicity (DON and AFB1).

摘要

真菌毒素是真菌产生的有毒代谢物,通常存在于动物饲料中,对人类和动物健康构成严重威胁。但目前的研究主要集中在无观察到不良效应水平的联合效应上。在体内研究中,将 6 周龄的 24 只小鼠分别暴露于脱氧雪腐镰刀菌烯醇(DON)0.1mg/kg BW、黄曲霉毒素 B1(AFB1)0.01mg/kg BW 和 DON 和 AFB1 的混合物(分别为 0.1mg/kg BW 和 0.01mg/kg BW)28 天。然后,将 DON 0.5μg/mL、AFB1 0.04μg/mL 和 DON 和 AFB1 的混合物(分别为 0.5μg/mL、0.04μg/mL)应用于体外猪肺泡巨噬细胞(PAMs)。我们的体内研究结果表明,DON 和 AFB1 联合无观察到不良效应水平给药降低了血清中的 IgA 和 IgG 水平,脾脏中 TNF-α、IFN-γ、IL-2 和 IL-6mRNA 表达以及脾中 T 淋巴细胞亚群水平(CD4 和 CD8)。此外,联合给药增加了 caspase-3、caspase-9、Bax、Cyt-c,降低了 Bcl-2 蛋白表达。综上所述,DON 和 AFB1 的联合无观察到不良效应水平可诱导免疫抑制,这可能与细胞凋亡有关。本研究为 DON 和 AFB1 的联合免疫毒性提供了新的见解。

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