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野鸦椿油,一种食用油掺杂物,在口服 28 天重复剂量毒性研究中可诱导 Balb/c 小鼠的全身性免疫抑制。

Argemone oil, an edible oil adulterant, induces systemic immunosuppression in Balb/c mice in an oral 28 days repeated dose toxicity study.

机构信息

Food, Drugs and Chemical Toxicology Group, CSIR- Indian Institute of Toxicology Research, India; Academy of Scientific and Innovative Research (AcSIR) CSIR-IITR Campus, Lucknow, India.

Central Pathology Laboratory, CSIR- Indian Institute of Toxicology Research, India.

出版信息

Chem Biol Interact. 2018 May 1;287:57-69. doi: 10.1016/j.cbi.2018.04.013. Epub 2018 Apr 12.

DOI:10.1016/j.cbi.2018.04.013
PMID:29655912
Abstract

Consumption of edible oils contaminated with Argemone oil (AO) leads to a clinical condition called "Epidemic dropsy". Earlier studies have reported that metabolism and oxidative stress primarily contributes to AO toxicity, however, the involvement of immune system has not been assessed so far. Therefore, the present study was undertaken to systematically assess the effect of AO exposure on the function of immune system in Balb/c mice. The repeated exposure of AO for 28 days caused prominent regression of spleen and thymus; severe inflammatory changes in spleen depicted by the loss of distinct follicles, increased megakaryocyte infiltration, and enhanced expression levels of inflammatory markers (iNOS & COX-2). At the functional level, AO exposure significantly abrogated the mixed lymphocyte reaction and mitogen-stimulated lymphoproliferative activity of T and B cells, which is reflective of profound lymphocyte dysfunction upon antigen exposure. In concordance with the loss in functional activity of lymphocytes in AO exposed animals, it was found the AO altered the relative percentage of CD3, CD4, and CD28  T cells. Further, there was a marked decrease in the relative distribution of cells with prominent MHC I and CD1d expression in AO exposed splenocytes. Moreover, reduced levels of immune stimulatory cytokines (TNF-α, IFN-γ, IL-2, IL-4, and IL-6), and increased levels of immunosuppressive cytokine IL-10 were detected in the serum of AO treated mice. Along with T and B cells, AO exposure also affected the phenotype and activation status of macrophages suggesting the inclination towards "alternative activation of macrophages". Altogether, these functional changes in the immune cells are contributing factors in AO induced immunosuppression.

摘要

食用油受到野鸦椿油(AO)污染,会导致一种被称为“流行性水肿”的临床症状。早期研究报告称,代谢和氧化应激是 AO 毒性的主要原因,但迄今为止尚未评估免疫系统的参与。因此,本研究旨在系统评估 AO 暴露对 Balb/c 小鼠免疫系统功能的影响。重复暴露于 AO 28 天会导致脾脏和胸腺明显退化;脾脏严重的炎症变化表现为明显的滤泡丧失、巨核细胞浸润增加以及炎症标志物(iNOS 和 COX-2)的表达水平增强。在功能水平上,AO 暴露显著削弱了混合淋巴细胞反应和 T 和 B 细胞有丝分裂原刺激的淋巴增生活性,这反映了抗原暴露后淋巴细胞功能严重受损。与 AO 暴露动物中淋巴细胞功能活性丧失一致,发现 AO 改变了 CD3、CD4 和 CD28 T 细胞的相对百分比。此外,AO 暴露的脾细胞中 MHC I 和 CD1d 表达明显的细胞相对分布显著减少。此外,在 AO 处理的小鼠血清中检测到免疫刺激性细胞因子(TNF-α、IFN-γ、IL-2、IL-4 和 IL-6)水平降低,而免疫抑制性细胞因子 IL-10 水平升高。与 T 和 B 细胞一样,AO 暴露还影响了巨噬细胞的表型和激活状态,表明巨噬细胞倾向于“替代激活”。总之,这些免疫细胞的功能变化是 AO 诱导免疫抑制的因素之一。

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