Institute of Food Sciences, National Research Council (CNR-ISA), Via Roma 64, 83100, Avellino, Italy.
Institute of Biosciences and Bioresources, National Research Council (CNR-IBBR), Naples, Italy.
Eur J Nutr. 2016 Mar;55(2):729-740. doi: 10.1007/s00394-015-0893-2. Epub 2015 Apr 4.
The beneficial effects of conjugated linoleic acid (CLA) mixture (cis9, trans11, c9; trans10, cis12, t10) against gliadin-induced toxicity in HLA-DQ8-transgenic mice (DQ8) have been associated with improved duodenal cytoprotective mechanisms [nuclear factor-E2-related factor-2, Nrf2; acylpeptide hydrolase (APEH)/proteasome]. The present study was aimed at investigating the ability of individual CLA isomers to improve the efficacy of these defensive mechanisms and to protect against duodenal injury caused by the combined administration of gliadin and indomethacin (GI).
Gluten-mediated enteropathy was induced in DQ8 mice by three intra-gastric administration of gliadin (20 mg kg(-1)/bw) and indomethacin (15 mg L(-1)) in drinking water for 10 days (GI). C9 or t10 CLA (520 mg kg(-1)/bw/day) were orally administered for 2 weeks. Pro-oxidant and toxic effects associated with GI treatment, anti-oxidant/detoxifying ability of c9 or t10-CLA and the protective effect induced by c9 pre-treatment (c9 + GI) were evaluated in DQ8 mice duodenum by combining enzymatic, immunoblotting, histological evaluation and quantitative real-time PCR assays.
GI treatment produces the time-dependent decline of the considered detoxifying mechanisms thus leading to pro-apoptotic and pro-oxidant effects. APEH/proteasome pathway was not markedly affected by individual CLA isomers, but duodenal redox status and activity/mRNA levels of Nrf2-activated enzymes were significantly improved by c9 administration. c9 pre-treatment protects against GI-mediated accumulation of oxidative stress markers, and histological examination reveals the increase of goblet cells number in mouse duodenum but induces only a partial recovery of APEH/proteasome activity.
The activation of and adaptive response by low doses of c9 supplementation prevents distinct signs of gliadin-induced enteropathy in DQ8 mice.
共轭亚油酸（CLA）混合物（顺式 9，反式 11，c9；反式 10，顺式 12，t10）对 HLA-DQ8 转基因小鼠（DQ8）中麦胶诱导的毒性的有益作用与改善十二指肠细胞保护机制[核因子-E2 相关因子 2（Nrf2）；酰肽水解酶（APEH）/蛋白酶体]有关。本研究旨在研究单独的 CLA 异构体是否能够提高这些防御机制的功效，并保护十二指肠免受麦胶和吲哚美辛（GI）联合给药引起的损伤。
通过三次胃内给予麦胶（20mgkg(-1)/bw）和吲哚美辛（15mgL(-1)）在饮用水中 10 天（GI），诱导 DQ8 小鼠发生肠病。口服给予 C9 或 t10-CLA（520mgkg(-1)/bw/天）2 周。通过联合酶学、免疫印迹、组织学评价和定量实时 PCR 分析，评估与 GI 治疗相关的促氧化剂和毒性作用、C9 或 t10-CLA 的抗氧化/解毒能力以及 C9 预处理（c9+GI）诱导的保护作用。
GI 治疗导致所考虑的解毒机制的时间依赖性下降，从而导致促凋亡和促氧化剂作用。APEH/蛋白酶体途径未受单独 CLA 异构体的显著影响，但 C9 给药可显著改善十二指肠氧化还原状态和 Nrf2 激活酶的活性/mRNA 水平。C9 预处理可防止 GI 介导的氧化应激标志物的积累，组织学检查显示小鼠十二指肠杯状细胞数量增加，但仅部分恢复 APEH/蛋白酶体活性。
低剂量 C9 补充的激活和适应性反应可防止 DQ8 小鼠中明显的麦胶诱导的肠病。
