Tunisian radish extract (Raphanus sativus) enhances the antioxidant status and protects against oxidative stress induced by zearalenone in Balb/c mice

Radish (Raphanus sativus) is a food plant known worldwide. From antiquity it has been used in folk medicine as a natural drug against many toxicants. Zearalenone (zen) is a non-steroidal estrogenic mycotoxin present in corn and food mixture for farm animals and it is hepatotoxic, hematotoxic, immunotoxic, nephrotoxic and genotoxic. The objectives of the present study were to assess the biological activity of radish extract and to evaluate the protective role of radish extract against the toxicity of zen in female Balb/c mice. Animals were divided into seven groups and treated orally for 10 days as follows: a control, an olive oil group, groups treated with radish extract alone (5, 10 and 15 mg kg(-1) b.w.), a group treated with zen (40 mg kg(-1) b.w.) and a group treated with zen plus the lowest dose of radish extract. The results indicate that radish extract improved the antioxidant status and had no significant effects on hematological and biochemical parameters tested or histology of the liver and kidney. Treatment with zen results in a significant increase in ALT, AST, ALP, BILT, BILD, CRE accompanied with significant changes in most of hematological parameters and the antioxidant enzyme activities, co-treatment of zen and the radish extract results in a significant reestablishment of hematological, serum biochemical parameters, and the histology of the liver and kidney. These findings suggest that radish extract is safe and can be overcome or, at least, significantly diminish zen effects.     

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.     

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.     

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.     

Effect of dairy products intake on breast cancer risk: A case-control study in Algeria

Objectives

The aim of this hospital-based case-control study is to evaluate the association between dairy products consumption and breast cancer risk. This relationship has not previously been studied in Algeria.

Proteasome inhibitors protect the steatotic and non-steatotic liver graft against cold ischemia reperfusion injury

Background

The dramatic shortage of organs leads to consider the steatotic livers for transplantation although their poor tolerance against ischemia reperfusion injury (IRI). Ubiquitin proteasome system (UPS) inhibition during hypothermia prolongs myocardial graft preservation. The role of UPS in the liver IRI is not fully understood. Bortezomib (BRZ) treatment at non-toxic doses of rats fed alcohol chronically has shown protective effects by increasing liver antioxidant enzymes. We evaluated and compared both proteasome inhibitors BRZ and MG132 in addition to University of Wisconsin preservation solution (UW) at low and non-toxic dose for fatty liver graft protection against cold IRI.

Experimental

Steatotic and non-steatotic livers have been stored in UW enriched with BRZ (100 nM) or MG132 (25 μM), for 24 h at 4 °C and then subjected to 2-h normothermic reperfusion (37 °C). Liver injury (AST/ALT), hepatic function (bile output; vascular resistance), mitochondrial damage (GLDH), oxidative stress (MDA), nitric oxide (NO) (e-NOS activity; nitrates/nitrites), proteasome chymotrypsin-like activity (ChT), and UPS (19S and 20S5 beta) protein levels have been measured.

Results

ChT was inhibited when BRZ and MG132 were added to UW. Both inhibitors prevented liver injury (AST/ALT), when compared to UW alone. BRZ increased bile production more efficiently than MG132. Only BRZ decreased vascular resistance in fatty livers, which correlated with an increase in NO generation (through e-NOS activation) and AMPK phosphorylation. GLDH and MDA were also prevented by BRZ. In addition, BRZ inhibited adiponectin, IL-1, and TNF alpha, only in steatotic livers.

Conclusion

MG132 and BRZ, administrated at low and non toxic doses, are very efficient to protect fatty liver grafts against cold IRI. The benefits of BRZ are more effective than those of MG132. This evidenced for the first time the potential use of UPS inhibitors for the preservation of marginal liver grafts and for future applications in the prevention of IRI.     

Geographical and social influences on genetic diversity within the Egyptian population: analyses of Alu insertion polymorphisms

Background: The geographical location of Egypt at the crossroads of several major cultural areas between North Africa and the Middle East has contributed to its population history.

Aim: To analyse the genetic structure of the population living in two geographical parts of Egypt.

Subjects and methods: A sample of 112 Egyptians from the North African part of Egypt (Ismailia sample) and a sample of 52 Egyptians from the Asian part Sinai, have been analysed using 10 Alu insertion polymorphisms.

Results: The results of the present study showed a significant genetic difference between the Sinai and Ismailia samples. The latter showed an evident genetic affinity with North African populations; whereas the Sinai sample was found to be genetically closer to the Middle East populations. The Sinai sample showed a low average heterozygosity, unlike that found in the Ismailia sample.

Conclusion: This study provides new insights into the genetic structure of the Egyptian population living in a land bridge between Africa and Asia. Results suggest a genetic discontinuity between the Sinai population and that of the North African part of Egypt. This discontinuity would have been maintained thanks to geo-climatic and social factors.     

Citrinin induces apoptosis in human HCT116 colon cancer cells through endoplasmic reticulum stress

The mycotoxin citrinin (CTN) is a natural contaminant of various human foods that may produce serious adverse health problems. Several studies demonstrated that citrinin exerts cytotoxic and genotoxic effects in both in vivo and in vitro systems. However, the precise mechanisms of action (MOA), particularly in intestinal cells remain unclear. The aim of the present study was to examine the precise MOA of citrinin in vitro. Data demonstrated that CTN significantly decreased the number of viable human intestinal HCT116 cells and induced apoptotic events including (1) decrease in Δ?m indicative of mitochondrial membrane permeabilization, (2) activation of caspase 3, (3) elevated production of reactive oxygen species (ROS) and (4) relative persistence of plasma membrane integrity. Further, the genetic deficiency of the pro-apoptotic protein Bax protected cells against CTN-induced apoptosis, indicating that Bax is required for CTN-mediated toxicity. It was also found that CTN triggered endoplasmic reticulum (ER) stress and activated different arms of the unfolded protein response (UPR) as demonstrated by increase in expression of GRP78 (glucose-regulated protein-78), GRP94 (glucose-regulated protein-94), GADD34 (growth arrest and DNA damage-inducible protein-34), the protein disulfide isomerase associated 6 (PDIA6), CHOP (C/EBP-homologous protein) and the splicing of XBP1 (X-Box Binding Protein 1). Pretreatment of cells with the chemical chaperone 4-phenylbutyrate (PBA), known to alleviate ER stress, prevented significantly the apoptotic process triggered by CTN. Taken together, these results suggest that CTN exerts its cytotoxic effects in HCT116 cells by inducing apoptosis, at least in part, through induction of ER stress.     

Could the Tokyo guidelines on the management of acute cholecystitis be adopted in developing countries? Experience of one center

Purpose

The Tokyo guidelines for diagnostic criteria and severity assessment of acute cholecystitis (AC), published in 2007, recommend early laparoscopic cholecystectomy (ELC) be done as soon as possible after the onset of symptoms. We conducted this study to analyze the changes in the therapeutic strategy for AC in a surgical center in Tunisia after the Tokyo guidelines were published.

Methods

Between January, 2005 and January, 2013, 649 patients underwent cholecystectomy for AC at the Department of Surgery, Mohamed Tahar Maamouri Hospital in Nabeul, Tunisia. The study period was subdivided into before (n = 192) and after (n = 457) the publication of the Tokyo guidelines, that is, prior to and including 2007, and from 2008 onward, respectively. We reviewed patient records retrospectively to collect demographic data, biochemical data, radiological findings, and postoperative outcomes. All these factors were compared between the groups.

Results

The duration of symptoms before surgery was significantly longer before 2008 (p = 0.018). ELC was significantly more frequent after 2008 (p = 0.001). Laparoscopic surgery was converted to open surgery in 16.1 % of patients before 2008 vs. 7.8 % of patients after 2008 (p = 0.02). There were no significant differences in bile duct injury or postoperative complications between the groups. The length of preoperative, postoperative, and total hospital stay was longer before 2008.

Conclusions

ELC is a safe and effective therapeutic strategy for AC. The Tokyo guidelines resulted in a significant increase in the number of ELCs being performed and significantly reduced preoperative and total hospital stay without increasing intra- and postoperative complications. Importantly, ELC reduced medical costs, which is crucial for a country with limited resources, such as Tunisia.