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E E Creppy

Publications and source records attributed to E E Creppy.

At least 19 recordsLinked to original sources
PubMed2006

Preliminary survey of ochratoxin A in millet, maize, rice and peanuts in Côte d'Ivoire from 1998 to 2002.

In a preliminary study, samples of millet (n =33) maize (n=41), rice (n=10) and peanuts (n=10) from Côte d'Ivoire were analysed for ochratoxin A (OTA) by HPLC with fluorimetric detection, followed by confirmation by cleavage of the OTA molecule using carboxypeptidase with HPLC separation and fluorimetric quantification of the released ochratoxin alpha (OTh). With the exception of four samples of peanuts, all samples showed OTA contamination, ranging from 3 to 1738 microg/kg. All cereals were contaminated and the OTA concentrations were in the range of 17-204 microg/kg for millet, 3-1738 microg/kg for maize, 9-92 microg/kg for rice and 0.6-64 microg/kg for peanuts, depending on the year of harvest. Most of the samples would not be accepted according to the EU regulatory limits for this mycotoxin. Following this survey, research for other mycotoxins and the evaluation of the exposure of the population is underway.

Algorithms↗
PubMed2005

Micronucleus test in mussels Perna perna fed with the toxic dinoflagellate Prorocentrum lima.

Micronucleus (MN) and other nuclear abnormalities have been measured in the hemocytes of mussels Perna perna to verify whether feeding mussels with different concentrations of Prorocentrum lima results in accumulation of levels of okadaic acid (OA) capable of inducing genotoxic effects at the chromosome level, as evidenced by micronuclei and nuclear abnormalities. Four groups of 12 mussels housed individually in aquaria containing filtered seawater were fed with different concentrations of P. lima. Another group collected directly from the production area served as outdoor control. A significantly higher frequency of MN and nuclear lesions was observed in hemocytes from the groups fed P. lima.

Animals↗
PubMed2005

Zearalenone induces chromosome aberrations in mouse bone marrow: preventive effect of 17beta-estradiol, progesterone and Vitamin E.

The cytogenetic effect of zearalenone (ZEN), a non-steroidal estrogenic mycotoxin, was evaluated in vivo, in mouse bone marrow cells, by assessing the percentage of cells bearing different chromosome aberrations. The studies included different conditions for animal treatment, as follows: (1) single intraperitoneal (ip) injection, (2) repeated ip injections, (3) pre-treatment for 24h with Vitamin E (Vit E), and (4) pre-treatment for 4h with 17beta-estradiol (17beta-Est) or progesterone (Prog). ZEN induced different types of chromosome aberrations, which was concentration-dependent (2-20 mg/kg bw). These doses corresponded to 0.4-4% of the LD50 in the mouse. Interestingly, when the dose of ZEN (40 mg/kg) was fractionated into four equivalent doses (4 x 10 mg/kg bw), into three doses (15 + 10 + 15 mg/kg bw), or into two equivalent doses (2 x 20 mg/kg bw), given every 24 h, the percentage of chromosome aberrations increased significantly. This finding suggests that ZEN proceeds by reversible binding on receptors that could become saturated, and that it damages the chromosomes in a 'hit and go' manner. Furthermore, pre-treatment of animals with 17beta-estradiol or progesterone significantly decreased the percentage of chromosome aberrations, suggesting that (i) these hormones bind to the same cytoplasmic receptors transported into the nucleus to elicit DNA damage, (ii) they may play a role in preventing chromosome aberrations induced by ZEN. Similarly, Vit E prevented these chromosome aberrations indicating that Vit E, previously reported to prevent most of the toxic effects induced by ZEN, may also bind to the same receptors.

Animals↗
PubMed2003

Micronucleus induction in mussels exposed to okadaic acid.

Some toxins present in the marine environment are capable of inducing mutagenicity and/or carcinogenicity. Among these toxins, okadaic acid (OA) is gaining considerable interest since it induces DNA based modifications at low concentrations and accumulates in filter-feeding marine animals, including those used for human consumption. This study aims to evaluate the genotoxicity of OA in the haemocytes of the mussel Perna perna, using the micronucleus assay. Fifty-four mussels were separated into three groups of 18 animals. One group received 0.3 microg of OA diluted in 10 microl of ethanol and ultrapure water while the other groups were considered as controls and were exposed to a solvent plus seawater mixture. A significantly higher frequency of micronuclei was observed in haemocytes from the OA-exposed group. There were no statistical differences between the two control groups.

Animals↗
PubMed2003

Magnesium content in seminal fluid as an indicator of chronic prostatitis.

Magnesium and zinc are both involved in a high number of enzymic activities vital for mammals. They are found in prostate in remarkably high concentrations and released into seminal fluid. Furthermore, drastic reduction of Zn and Mg concentrations in the semen fluid may lead to disorders in male fertility. We aimed to analyse the differences in Mg and Zn levels in the seminal plasma of 213 males including 48 normozoospermic, 30 azoospermic, 28 oligoasthenozoospermic, 22 asthenozoospermic and 85 chronic prostatitis. Mg and Zn concentrations were measured using an atomic absorption spectrophotometer. While zinc levels did not show correlation either with the volume of the sperm or the percentage of pathological forms, magnesium concentrations in seminal plasma were significantly decreased in chronic prostatitis patients as compared to other groups or normozoospermic patients (p<0.001). We propose therefore magnesium as a marker of prostatitis.

Chronic Disease↗
PubMed2002

Ochratoxin A in human plasma in Morocco: a preliminary survey.

Available epidemiological information seems to indicate that Balkan endemic nephropathy is associated with consumption patterns involving foodstuffs contaminated with ochratoxin A (OTA) and with a higher frequency of OTA-positive blood samples. The aim of this preliminary study was to assess OTA concentrations in human plasma in Morocco. Therefore, samples from 309 healthy volunteers (213 males, 96 females) were analysed. The analyses revealed that 60% of the human plasma sampled was positive for OTA (61.5% in the male and 56% in the female population), and an average concentration of 0.29 ng/mL (0.31 ng/mL in males, 0.26 ng/mL in females). The highest concentration found was 6.59 ng/mL. The results suggest that the Moroccan population is exposed to OTA, even though the OTA plasma levels are lower than that reported in some North African countries.

Adolescent↗
PubMed2001

DNA breaks and cell cycle arrest induced by okadaic acid in Caco-2 cells, a human colonic epithelial cell line.

Okadaic acid (OA) is a shellfish toxin produced by dinoflagellates, in mussels. It is a potent tumour promoter and represents a potential threat to human health even at low concentrations. OA targets mainly the gastrointestinal tract in acute poisoning, causing diarrhoea. Therefore the present investigations were designed to study the ability of okadaic acid to induce cytotoxicity and DNA lesions in a human colonic cell line (Caco-2). Incubation of Caco-2 cells with OA (3.75-60 ng/ml, i.e. 4.6 x 10(-3)-7.5 x 10(-2) microM) causes a significant reduction in cell viability. Moreover, okadaic acid inhibits protein and DNA synthesis with, respectively, IC50 of 16 and 6.5 ng/ml after 24 h incubation. It also provokes cell cycle arrest, characterised by an increase in the number of S phase cells, correlated with a significant decrease in G0/G1 phase cells at high concentration. One of the main results obtained in these investigations is the apoptosis induced by OA in Caco-2 cells of intestinal origin, shown by DNA laddering in agarose gel electrophoresis (250-1000 base pairs). OA also induces clastogenic effects evaluated by DNA fragmentation analysis using the method of Higuchi and Aggarwal (52% for 60 ng/ml) and comet assay (increase of the frequency of comets and their tails length). Therefore, the cell death induced by OA seems clearly to be concentration-dependent after 24 h of incubation. The cytotoxic properties of okadaic acid and its ability to damage DNA result in cell death, mainly by apoptosis. Since consumption of shellfish contaminated with acceptable okadaic acid concentrations exposes colonic cells to harmful concentrations of this toxin, the possibility that OA would display its toxic effects on intestinal cells in vivo should be evaluated in human primary intestinal cells and human intestinal slices for cytotoxic effects, DNA fragmentation and apoptosis.

Caco-2 Cells↗
PubMed2001

Toxicokinetics of ochratoxin A in vervet monkeys (Cercopithecus aethiops).

The toxicokinetics of ochratoxin A were investigated in vervet monkeys (Cercopithecus aethiops). Three female monkeys were treated intravenously with ochratoxin A at doses, respectively, of 0.8, 1.5 and 2 mg/ kg body weight (BW). Blood and urine samples were collected over a period of 21 days. Plasma and urine extracts were analysed by high-performance liquid chromatography (HPLC) with either fluorescence or negative ion electrospray ionization mass spectrometric detection. The clearance of ochratoxin A from plasma followed a two-compartment model. The elimination half-life of ochratoxin A in the monkeys was determined to be 19-21 days and the average total body clearance was 0.22 +/- 0.07 ml/h per kg and the average apparent distribution volume of the central compartment was 59 +/- 9 ml/kg and the peripheral compartment was 59 +/- 20 ml/kg. No evidence was found for any metabolic conversion of ochratoxin A.

Animals↗
PubMed2001

Aspartame prevents the karyomegaly induced by ochratoxin A in rat kidney.

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus ochraceus as well as other moulds. This mycotoxin contaminates animal feed and food. OTA is immunosuppressive, genotoxic, teratogenic, carcinogenic and is nephrotoxic in all animal species studied so far. OTA inhibits protein synthesis and induces lipid peroxidation. Since it seems impossible to avoid completely contamination of foodstuffs by toxigenic fungi, it is necessary to investigate the possible ways of limiting such toxicity. An attempt to prevent OTA-induced nephrotoxic and genotoxic effects, mainly the karyomegaly, has been made in vivo using aspartame (L-aspartyl-L-phenylalanine methyl ester), a structural analogue of both OTA and phenylalanine. Aspartame (25 mg/kg body weight) prevented most of the nephrotoxic effects induced by OTA (289 microg/kg body weight). It also showed some utility in preventing morphological and histological damage, mainly the karyomegaly. The protective effects of aspartame on OTA-induced nephrotoxicity could be based on several mechanisms related to competitive binding to plasma proteins, to transport or tissue distribution in the kidney or to the elimination of the toxin in the urine.

Animals↗
PubMed2001

Experimental mycotoxic nephropathy in pigs provoked by a diet containing ochratoxin A and penicillic acid.

Mycotoxic nephropathy was induced in 18 young pigs by diets contaminated with strains of Aspergillus ochraceus containing ochratoxin A (OTA) and penicillic acid (PA) at levels corresponding to those naturally encountered in animal feeds in Bulgaria. Haematological and biochemical parameters, as well as the morphological and ultrastructural changes in various internal organs, and especially in the kidneys, were examined at different stages of development of the disease. A mottled surface of the kidneys was only seen in pigs exposed to a mouldy diet containing 180 ppb OTA for 3 months, but microscopic lesions, as well as changes in various haematological and biochemical parameters, were observed in all groups exposed to the same mouldy diet containing only 90 or 180 ppb OTA. Histological examination showed two types of change: degenerative changes affecting the epithelial cells of the proximal tubules, which predominated at the initial stage, and proliferative changes in the interstitium, which predominated at the later stage of the disease. Telangiectasis and lymph stasis were also seen, as well as degenerative changes in the capillary endothelium. The characteristic renal lesions were similar to those observed in spontaneous cases of mycotoxic porcine nephropathy in Bulgaria, but they were a little different from the classic Danish porcine nephropathy. The enhanced toxicity of OTA in our study may be due to a synergistic effect between OTA and PA or to some other unknown metabolites produced by the same ochratoxinogenic strains of A. ochraceus.

Animal Feed↗
PubMed2001

Ochratoxin A in beverages from Morocco: a preliminary survey.

In a preliminary study, samples of Moroccan wines (n = 30), beers (n = 5) and fruit juices (n = 14) were assayed for ochratoxin A (OTA) by HPLC with fluorimetric detection, followed by confirmation by cleavage of the OTA molecule using carboxypeptidase with HPLC-fluorimetric determination of ochratoxin alpha (OT alpha). All the wine samples were contaminated, and the overall median OTA concentration was 0.65 microg/l (range 0.028-3.24 microg/l). One of the 14 samples of fruit juices was contaminated with a concentration of 1.16 microg/l, whereas none of the five beer samples was contaminated. This is the first report on the occurrence of OTA in various beverages from Morocco.

Beer↗
PubMed2001

Lipid peroxidation as pathway of aluminium cytotoxicity in human skin fibroblast cultures: prevention by superoxide dismutase+catalase and vitamins E and C.

Lipid peroxidation is one of the main manifestations of oxidative damage and has been found to play an important role in the toxicity and carcinogenicity of many xenobiotics. In the present study, we investigated the possible induction of lipid peroxidation by aluminium in human foreskin fibroblast cultures by assaying the malondialdehyde (MDA) produced inside the cells. The MDA-thiobarbituric acid (TBA) adduct was assayed by HPLC using fluorometric quantification after extraction in n-butanol. Lactate dehydrogenase (LDH) release was used as a marker of aluminium toxicity. MDA production was significantly increased after 24 h incubation with aluminium and paralleled LDH release. Superoxide dismutase (SOD)+catalase and vitamins C and E added in the culture medium as oxygen radical and free radical scavengers were efficient in preventing MDA production by aluminium, indicating that oxidative processes are one of the main pathways whereby this metal induces cytotoxicity. The latter is also largely prevented, thus confirming the link between oxidative stress induced by aluminium and its cytotoxicity in human skin fibroblasts.

Aluminum↗
PubMed2000

Implications of oxidative stress and inflammatory process in the cytotoxicity of capsaicin in human endothelial cells: lack of DNA strand breakage.

Capsaicin, a natural product of Capsicum species is known to induce excitation of nociceptive terminals involved in pain perception. Nevertheless, it is utilized by topical application in humans, giving rise to blood capsaicin concentration up to 10-20 microM. The effect of capsaicin on human endothelial cells ECV 304 has been investigated. The cytotoxicity and inflammatory properties of capsaicin were evaluated by measuring the capsaicin-stimulated release of soluble intercellular adhesion molecule-1 levels (sICAM-1) into the culture medium; production of reactive oxygen species measured by quantification of lipoperoxidation in endothelial cell membranes; and genotoxicity measured using the comet assay and the DNA fragmentation assay. The concentration inhibiting protein synthesis by 50% after 24-h incubation was found to be 175 microM. Capsaicin induced an increase of sICAM-1 release into the culture medium at concentration >/=100 microM. Lipoperoxidation measured by malondialdehyde production increased at capsaicin concentration >/=200 microM. The comet test and DNA fragmentation assay clearly suggested that capsaicin does not induce significant DNA strand breaks within the range of concentrations used. Because the inflammatory reaction and lipid peroxidation may affect cellular functions and lead to cell death, the present data may have important implications for the possible health threats of capsaicin, specially in the case of unreasonable use of capsaicin preparations in pathological situations.

Capsaicin↗
PubMed2000

Epigenetic properties of fumonisin B(1): cell cycle arrest and DNA base modification in C6 glioma cells.

Fumonisin B(1) produced by the fungus Fusarium moniliforme is a member of a new class of sphinganine analogue mycotoxins that occur widely in the food chain. Epidemiological studies associate FB(1) with human oesophageal cancer in China and South Africa. FB(1) also causes acute pulmonary edema in pigs and equine leucoencephalomalacia. This disease is thought to be a consequence of inhibition by FB(1) of cellular ceramide synthesis in cells. To investigate further on this pathogenesis, the effect of FB(1) was studied on cell viability (3 to 54 microM of FB(1)), protein (2.5 to 20 microM of FB(1)) and DNA syntheses (2.5 to 50 microM of FB(1)), and cellular cycle (3 to 18 microM of FB(1)) of rat C6 glioma cells after 24 h incubation. The results of the viability test show that FB(1) induces 10 +/- 2% and 47 +/- 4% cell death with, respectively, 3 and 54 microM, in C6 cells. This cytotoxicity induced by FB(1) was efficiently prevented when the cells were preincubated 24 h with vitamin E (25 microM). FB(1) displays epigenetic properties since it induced hypermethylation of the DNA (9-18 microM). Inhibition of protein synthesis was observed with FB(1) with an IC(50) of 6 microM showing that C6 glioma cells are very sensitive to FB(1); however, the synthesis of DNA was only slightly inhibited, up to 20 microM of FB1. The flow cytometry showed that the number of cells in phase S decreased significantly as compared to the control p = 0.01 from 18. 7 +/- 2.5% to 8.1 +/- 1.1% for 9 microM FB(1). The number of cells in phase G(2)/M increased significantly as compared to the control (p </= 0.05) from 45.7 +/- 0.4% to 54.8 +/- 1.1% for 9 microM FB(1), whereas no change occurs in the number of cells in the phase G(0)/G(1). These results show that cytotoxic concentrations of FB(1) induce cellular cycle arrest in phase G(2)/M in rat C6 glioma cells possibly in relation with genotoxic events.

Animals↗
PubMed2000

Distribution of mapacalcine receptors in the central nervous system of rat using the [125I]-labeled mapacalcine derivative.

Mapacalcine is a dimeric protein of Mr 19041 extracted from the marine sponge Cliona vastifica. Electrophysiological and pharmacological approaches have demonstrated that mapacalcine was blocking a calcium channel different from N-, L-, P-, T- or Q-type calcium channels on mouse intestinal smooth muscle. Recently a [125I]-labeled derivative of mapacalcine has been synthesized and characterized as a tool usable as a probe to investigate mapacalcine receptors. On rat brain membranes, it binds to its receptor with a K(d)=0.35 nM and a maximal binding capacity of 706 fmol/mg protein. We use here [125I]-mapacalcine to study the mapping of its receptors in the rat brain. Data obtained show a practically homogeneous labeling of the brain. Our experiments suggest that mapacalcine receptors are present on neuronal and glial cells. Interestingly, choroid plexus demonstrates a high density of mapacalcine receptors. These data would suggest that mapacalcine sensitive calcium channels could be involved in the control of calcium homeostasis of the cerebrospinal fluid.

Animals↗
PubMed2000

Cytotoxicity of capsaicin in monkey kidney cells: lack of antagonistic effects of capsazepine and Ruthenium red.

Capsaicin is a natural product of Capsicum peppers, excitatory effects of which have been shown to be mediated by the recently cloned vanilloid receptor 1 (VR1). Since previous studies have shown that capsaicin inhibits protein synthesis, experiments were performed to investigate whether this effect is mediated by VR1 receptor on cultured monkey kidney cells (Vero cells). The capsaicin uptake was assessed in cellular homogenate and in medium by high-performance liquid chromatography (HPLC) separation and quantification on C18 reverse-phase column and fluorescence detection. Toxic effects were assessed by incorporation of [3H]L-leucine into cellular proteins in the presence of capsazepine, the VR1 vanilloid receptor antagonist and Ruthenium red or tyrosine or calcium. Capsazepine (1 to 256 microM) did not modify the uptake rate of capsaicin for incubation times up to 24 h and did not antagonize capsaicin-induced protein synthesis inhibition. It rather inhibited protein synthesis per se from 100 to 256 microM. Ruthenium red which blocks mitochondrial calcium uptake, inhibited protein synthesis and did not antagonise or increase synergistically the effects of capsaicin. Interestingly in a medium deprived of calcium and supplemented by calcium chloride (10-50 microM) the protein synthesis inhibition induced by capsaicin is antagonised somehow. There was no prevention of capsaicin diffusion into the cells. Tyrosine, which seems to be the best preventive agent of capsaicin inhibitory effects, prevents its metabolism but not its diffusion. Capsaicin might enter cells by diffusion and interfere with protein synthesis machinery by competition with tyrosine which in turn prevents the metabolism of capsaicin. The results of the present study suggest that cell responses to capsaicin may be transduced through at least two molecular pathways, one involving VR1, since the receptor antagonist capsazepine fails to prevent the inhibitory effect of capsaicin in Vero cells of renal origin.

Animals↗
PubMed2000

Combined effects of okadaic acid and cadmium on lipid peroxidation and DNA bases modifications (m5dC and 8-(OH)-dG) in Caco-2 cells.

Okadaic acid (OA) is a marine toxin, a tumour promoter and an inducer of apoptosis. It mainly inhibits protein-phosphatases, protein synthesis and enhances lipid peroxidation. Cadmium (Cd) is known to be carcinogenic in animals and humans (group 1 according to the International Agency for Research on Cancer (IARC) classification). Cd also induces oxidative stress in living organisms. Since they are sometimes found simultaneously in mussels, we have evaluated in the present investigation, the lipid peroxidation, as malondialdehyde (MDA) production, in the variation of the ratios of 8-(OH)-dG/10(5)dG and m5dC/(dC + m5dC) induced by OA and/or Cd in Caco-2 cells. When cells were treated exclusively by OA (15 ng/ml) or Cd (0.625 and 5 microg/ml) for 24 h, protein synthesis was inhibited (by 42 +/- 5%, 18 +/- 13%, and 90 +/- 4% respectively) while MDA production was 2,235 +/- 129, 1710 +/- 20, and 11,496 +/-1,624 pmol/mg protein respectively. In addition, each toxicant induced modified bases in DNA; increases in oxidised bases and methylated dC. The combination of OA and cadmium was more cytotoxic and caused more DNA base modifications; the ratio m(5)dC/(m(5)dC + dC) was increased from 3 +/- 0.15 to 9 +/- 0.15 and the ratio 8-(OH)-dG/10(5) dG also (from 36 +/- 2 to 76 +/- 6). The combination of OA and Cd also increased the level of MDA (1,6874 +/- 2,189 pmole/mg protein). The present results strongly suggest that DNA damage resulting from the oxidative stress induced by these two toxicants may significantly contribute to increasing their carcinogenicity via epigenetic processes.

5-Methylcytosine↗