Lactobacillus plantarum MON03 counteracts zearalenone génotoxicty in mice: Chromosome aberrations, micronuclei, DNA fragmentation and apoptotique gene expression

Abstract

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 × 109 CFU/L, ∼2 mg/kg and 4 × 109 CFU/L, ∼4 mg/kg) was added alone or in combination with a toxic intragastric ZEN (40 mg/kg representing 8% of LD50) 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.