Zearalenone nephrotoxicity: DNA fragmentation, apoptotic gene expression and oxidative stress protected by Lactobacillus plantarum MON03

Zearalenone nephrotoxicity: DNA fragmentation, apoptotic gene expression and oxidative stress protected by Lactobacillus plantarum MON03
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DOI:
10.1016/j.toxicon.2019.12.004
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发表时间:
2020-02-01
期刊:
影响因子:
2.8
通讯作者:
Abbes, Samir
Abbes, Samir
中科院分区:
医学4区
文献类型:
--
作者:
Ben Salah-Abbes, Jalila;Belgacem, Hela;Abbes, Samir

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本研究旨在检测乳杆菌活菌MON03细胞在液体培养中降解玉米赤霉烯酮(Zen)的能力,并探讨其对受Zen污染的Balb/c小鼠肾脏损伤的预防作用。观察肾组织DNA片段化、Bcl2、Bax基因表达、caspase 3活性、炎症调节因子基因表达水平及组织学变化。将雌性Balb/c小鼠随机分为4组(10只/组),每天灌胃乳酸菌(植物乳杆菌MON03)2×10(9)cfu/L(相当于2 mg/kg体重)、单用Zen(40 mg/kgbw)、Zen(40 mg/kgbw)+乳酸菌(L.ants MON03,2×10(9)cfu/L,相当于2 mg/kg)。对照组接受车辆接送。实验结束后,测定肾脏DNA片段化、Bcl2和Bax基因表达、caspase-3活性、丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-Px)含量,以及总抗氧化活性(TAC)和炎症调节细胞因子(IL-10、IL-6、TNF-α)mRNA水平的变化。结果表明,Zen可导致肾细胞caspase-3活性、MDA和IL-10、IL-6、TNF-α和Bax mRNA水平升高。但可降低TAC含量,下调GSH-Px、CAT和Bcl-2mRNA的表达。Zen加LP联合治疗可抑制肾组织DNA片段化,使肾组织丙二醛(MDA)和过氧化氢酶(CAT)水平正常化,GSH-Px和CAT表达上调,所分析细胞因子的mRNA水平正常化。结论:Zen可能对肾脏有毒性作用。此外,可以看出,使用LP可以诱导对ZEN的氧化应激和肾脏毒性的保护作用,部分是通过粘连(因此可能会降低生物利用度)。
The present study was conducted to determine the abilities of the living Lactobacillus plantation MON03 cells to degrade Zearalenone (ZEN) in liquid medium, and to elucidate the preventive effect in ZEN-contaminated balb/c mice showing kidney damage. The DNA fragmentation, Bcl-2 and Bax gene expression, caspase-3 activity, mRNA level of inflammation-regulating cytokines and histology of kidney tissues were examined. Female Balb/c mice were divided into four groups (10/group) and treated daily for 2 wk by oral gavage with lactic acid bacteria (L. plantarum MON03) 2 x 10(9) CFU/L, similar to 2 mg/kg only, ZEN (40 mg/kg BW) only, ZEN (40 mg/kg BW) + lactic acid bacteria (L. plantarum MON03, 2 x 10(9) CFU/L, similar to 2 mg/kg). Control group received vehicle. At the end of experiment, the kidney was collected for the determination of DNA fragmentation, Bcl-2 and Bax gene expression,caspase-3 activity, Malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) content, as well as for any alterations in expression of total antioxidant activity (TAC) and mRNA levels of inflammation-regulating cytokines (e.g., IL-10, IL-6, TNF-alpha).The results indicated that, kidney cells exposure to ZEN led to increased caspase-3 activity, MDA, and IL-10, IL-6, TNF-alpha and Bax mRNA levels, but decreased TAC content and down-regulated expression of GSH-Px and CAT and Bcl-2 mRNA. Co-treatment with ZEN plus LP suppressed the levels of DNA fragmentation; normalized kidney MDA and increased CAT levels, up-regulated expression of GSH-Px and CAT, and normalized mRNA levels of the analyzed cytokines. It's concluded that ZEN might have toxic effects in kidney. Further, it can be seen that use of LP induced protective effects against the oxidative stress and kidney toxicity of ZEN in part through adhesion (and so likely diminished bioavailability).