Different apoptotic pathways induced by zearalenone, T-2 toxin and ochratoxin A in human hepatoma cells

Mycotoxins, secondary metabolites produced by moulds, have been shown to cause diverse toxic effects in animals and are also suspected of disease causation in humans. The present study compares the molecular mechanisms of the toxicity of zearalenone (ZEN), T-2 toxin and ochratoxin A (OTA) in human hepatoma cells HepG2. The three mycotoxins-induced a caspase-dependent mitochondrial apoptotic pathway. The mitochondrial alterations include: bax relocalisation into the mitochondrial outer membrane, loss of the mitochondrial transmembrane potential, PTPC opening, and cytochrome c (but not AIF) release. In the presence of ZEN and T-2 toxin, reactive oxygen species (ROS) level was highly increased at an early stage even before mitochondrial alterations were observed, whereas OTA-induced only O(2)(-) generation among total ROS. This ROS production appears as a consequence of mitochondrial alterations. HepG2 cell treatment with the p53 inhibitor pifithrin-alpha (PFT) and western blot analysis suggested that both ZEN and OTA, but not T-2 toxin, trigger a p53-dependent apoptotic pathway. These results clearly point to a central role of mitochondria in the apoptotic process induced by ZEN, T-2 toxin and OTA and provide new insights into the molecular mechanisms by which these mycotoxins might promote hepatotoxicty.     

Cactus (Opuntia ficus-indica) cladodes prevent oxidative damage induced by the mycotoxin zearalenone in Balb/C mice.

Zearalenone (ZEN) is one of the most widely distributed fusarial mycotoxins which is encountered at high incidence in many foodstuffs. ZEN was associated with different reproductive disorders in animals. Several in vivo studies have shown that ZEN is hepatotoxic, haematotoxic and causes several alterations of immunological parameters. Furthermore, evidence of its cytotoxicity and genotoxicity has recently emerged from several reports. The aim of the current study was (i) to find out whether oxidative stress could be relevant for ZEN induced toxicity in vivo using Balb/c mice and (ii) to evaluate the safety and efficacy of cactus cladodes Opuntia ficus to prevent the deleterious effects of ZEN. To this end, the effect of a single dose of ZEN (40 mg/kg b.w.) alone and with extract of cactus cladodes (25, 50 and 100 mg/kg b.w.) on the induction of oxidative stress was monitored in kidney and liver by measuring the MDA level, the protein carbonyls generation, the catalase activity and the expression of the heat shock proteins (Hsp). Our results clearly showed that ZEN induced significant alterations in all tested oxidative stress markers. Oxidative damage seems to be a key determinant of ZEN induced toxicity in both liver and kidney of Balb/c mice. The combined treatment of ZEN with the lowest tested dose of cactus extracts (25 mg/kg b.w.) showed a total reduction of ZEN induced oxidative damage for all tested markers. It could be concluded that cactus cladodes extract was effective in the protection against ZEN hazards. This could be relevant, particularly with the emergent demand for natural products which may counteract the detrimental effects of oxidative stress and therefore prevent multiple human diseases.     

School retardation in a suburban community of Tunisian Sahel

This study tries to assess the prevalence of the school retardation in a suburban community of the Tunision Sahel, to identify its determinants factors and to propose a preventive strategy. It is a transverse investigation having interested 540 registered pupils at the 6th year in six randomly chosen primary schools of Kalaa Kebira (Sousse-Tunisia). Showed that the prevalence of the school retardation is 29%. It appears therefore that the school retardation is especially a complex problem dominated by the socio-educational factors requiring the orientation of the school health team toward a multi sectorial intervention integrating teachers, social workers and representatives of parents.     

Individual and combined effects of ochratoxin A and citrinin on viability and DNA fragmentation in cultured Vero cells and on chromosome aberrations in mice bone marrow cells

Ochratoxin A (OTA) and citrinin (CTN) are two common contaminant mycotoxins which can occur jointly in a wide range of food commodities. Both mycotoxins have several toxic effects but share a significant nephrotoxic and carcinogenic potential since OTA and CTN were reported to be responsible for naturally occurring human and animal kidney diseases and tumors. Considering the concomitant production of OTA and CTN, it is very likely that humans and animals are always exposed to the mixture rather than to individual compounds. Therefore, the aim of the present study was to investigate, in vivo and in vitro, whether DNA damage is enhanced by combination of both mycotoxins as compared to their effect separately. To this end, we have assessed their effects individually or combined on cell proliferation and DNA fragmentation in cultured Vero cells and in vivo by monitoring the induction of chromosome aberrations. Our results clearly showed that cultured renal cells respond to OTA and CTN exposure by a moderate and weak inhibition of cell proliferation, respectively. However, when combined, they exert a significant increase in inhibition of cell viability. Similar results were found for the investigated genotoxicity endpoints (DNA fragmentation and chromosome aberrations). Altogether, our study showed that OTA and CTN combination effects are clearly synergistic. The synergistic induction of DNA damage observed with OTA and CTN taken concomitantly could be relevant to explain the molecular basis of the renal diseases and tumorogenesis induced by naturally occurring mycotoxins.     

Detection of ica genes and slime production in a collection of Staphylococcus epidermidis strains from catheter-related infections in neutropenic patients

Slime production, principal virulence factor of Staphylococcus epidermidis associated with catheter-related infections is mediated by icaADBC operon wich expression is subject to phase variation. Reversible transposition of IS256 element into this operon is one of the most important mechanisms of biofilm phenotypic variation. Our study compared 28 S. epidermidis strains from catheter-related infection to 28 strains from nasal carriage concerning slime production on Congo red agar plate and ica genes and IS256 presence by PCR. ica operon was present among all slime-producing strains, and was absent among slime-negative strains. Only 79% of ica-positive strains were slime producers and no insertion of IS256 element was detected inside ica genes. A significative difference was found between catheter-related infections strains and commensal ones in terms of oxacillin (67,8 versus 35,7%) and ofloxacin resistance (75 versus 35,7%), slime production (64,2 versus 28,5%), phase variability (46,4 versus 7,1%) and ica genes presence (82,1 versus 35,7%). Our study demonstrates the role of ica genes, of phenotypic variability of slime production and antibiotic multiresistance as virulence factors of S. epidermidis associated with catheter-related infections; it confirms also the complexity and the diversity of regulation mechanisms implicated in biofilm formation.