Belgacem Hela, Ben Salah-Abbès Jalila, Ezzdini Khawla, A Abdel-Wahhab Mosaad, Zinedine Abdellah, Abbès Samir
Laboratory of Genetic, Biodiversity and Bio-Ressources Valorization, University of Monastir, Monastir, Tunisia.
Food Toxicology & Contaminants Department, National Research Center, Dokki, Cairo, Egypt.
Mutat Res Genet Toxicol Environ Mutagen. 2019 Apr;840:11-19. doi: 10.1016/j.mrgentox.2018.12.008. Epub 2018 Dec 15.
Zearalenone (ZEN) is a potent estrogenic metabolite produced by some Fusarium species. No treatment has been successfully employed to get rid against ZEN contained in foods and/or mitigates its genotoxicity. This study was conducted to evaluate the ability of lactic acid bacteria, isolated from Tunisia traditional butter, Lactobacillus plantarum MON03 (LP) to protect mice against cytotoxicity and genotoxicity induced by ZEN. Two doses of LP (2 × 10 CFU/L, ∼2 mg/kg and 4 × 10 CFU/L, ∼4 mg/kg) was added alone or in combination with a toxic intragastric ZEN (40 mg/kg representing 8% of LD) dose daily for 2 wk by oral gavage. The control group received distilled water. The positive control groups received Colchicin (4 mg/kg bw) for the micronucleus assay and mitomycin C (1 mg/kg bw) for the chromosome aberrations assay. 48 h after treatment, the small intestines, femur and tibia are dissected out. Small intestines were collected for the determination of DNA fragmentation, genes expression and target proteins content. The results show that ZEN was cytotoxic and genotoxic to mice as indicated by the increase in frequencies of polychromatic erythrocytes micronucleated (PCEMN) and chromosomal aberrations in bone marrow cells. In the small intestine ZEN was increased DNA fragmentation, down regulated the expressions of caspase-3, caspase-9, and Bax as well as up-regulated the expression of Bcl-2 and their target proteins. The simultaneous intragastric administration of LP with ZEN resulted in a decrease of PCEMN number and chromosomal aberrations frequency and in an increase of polychromatic erythrocytes (PCE) in bone marrow cells compared with the group treated with ZEN alone. In addition, LP succeeded to alleviate the disturbances in DNA fragmentation and the expression of these genes and their target proteins. It could be concluded that the use of LP induced protective effects against genotoxicity of ZEN in part through adhesion and so likely diminished its bio-availability in gastro-intestinal tract.
玉米赤霉烯酮（ZEN）是某些镰刀菌属产生的一种强效雌激素代谢产物。目前尚未成功采用任何治疗方法来去除食品中所含的ZEN和/或减轻其遗传毒性。本研究旨在评估从突尼斯传统黄油中分离出的植物乳杆菌MON03（LP）保护小鼠免受ZEN诱导的细胞毒性和遗传毒性的能力。通过口服灌胃，单独添加两剂LP（2×10⁹CFU/L，约2mg/kg和4×10⁹CFU/L，约4mg/kg）或与有毒的胃内ZEN（40mg/kg，占LD的8%）剂量联合，每日给药2周。对照组接受蒸馏水。阳性对照组在微核试验中接受秋水仙碱（4mg/kg体重），在染色体畸变试验中接受丝裂霉素C（1mg/kg体重）。治疗48小时后，取出小肠、股骨和胫骨。收集小肠用于测定DNA片段化、基因表达和靶蛋白含量。结果表明，多染红细胞微核（PCEMN）频率和骨髓细胞染色体畸变增加，表明ZEN对小鼠具有细胞毒性和遗传毒性。在小肠中，ZEN增加了DNA片段化，下调了半胱天冬酶-3、半胱天冬酶-9和Bax的表达，同时上调了Bcl-2及其靶蛋白的表达。与单独用ZEN处理的组相比，LP与ZEN同时胃内给药导致PCEMN数量减少和染色体畸变频率降低，骨髓细胞中多染红细胞（PCE）增加。此外，LP成功减轻了DNA片段化以及这些基因及其靶蛋白表达的紊乱。可以得出结论，使用LP部分通过黏附诱导了对ZEN遗传毒性的保护作用，因此可能降低了其在胃肠道中的生物利用度。
