Biomedical subjects

Marcel Castegnaro

Publications and source records attributed to Marcel Castegnaro.

6 recordsLinked to original sources

PubMed2006

Balkan endemic nephropathy: role of ochratoxins A through biomarkers.

Several studies implicated mycotoxins, in endemic kidney disease geographically limited to Balkan region (Balkan endemic nephropathy (BEN)). In Bulgaria, much higher prevalence of ochratoxin A (OTA), exceeding 2 microg/L, was observed in the blood of affected population. OTA is found more often in the urine of people living in BEN-endemic villages. To confirm and quantify exposure to OTA in Vratza district, we followed up OTA intake for 1 month, OTA in blood and urine from healthy (20-30 years old) volunteers, from two villages with high risk for BEN disease. Food samples were collected daily, blood and urine at the beginning of each week. Relations between increasing OTA intake, blood concentration and elimination of OTA in urine have been studied in rats. Average weekly intake of OTA varies from 1.9 to 206 ng/kg body weight, twice tolerable weekly intake recommended by JECFA. OTA blood concentrations are in the same range as previously reported in this region with concentrations reaching 10 microg/L. Weekly OTA food intake is not directly correlated with blood and urine concentrations. Biomarkers of biological effects such as DNA adducts were detected in patients affected by urinary tract tumours (UTT) and in rat study. All these plead for the implication of OTA, in BEN and UTT.

Adult↗

PubMed2006

Evidence of a new dechlorinated ochratoxin A derivative formed in opossum kidney cell cultures after pretreatment by modulators of glutathione pathways: correlation with DNA-adduct formation.

Ochratoxin A (OTA), a nephrotoxic mycotoxin probably implicated in human Balkan endemic nephropathy and associated urothelial tumors, induces renal carcinomas in rodents and nephrotoxicity in pigs. OTA induces DNA-adduct formation, but the structure of the adducts and their role in nephrotoxicity and carcinogenicity have only partly been elucidated. In vivo, 2-mercaptoethane sulfonate (MESNA) protects rats against OTA-induced nephrotoxicity but not against carcinogenicity, indicating two different mechanisms leading to nephrotoxicity or carcinogenicity. To better understand how DNA-adduct could be generated, opossum kidney cells (OK) have been treated by OTA alone or in presence of several compounds such as MESNA or N-acetylcysteine (another agent that, like MESNA, reduces oxidative stress by increasing of free thiols in kidney), buthionine sulfoximine (BSO) (an inhibitor of glutathione-synthase), and alpha amino-3-chloro-4,5-dihydro-5-isoxazole acetic acid (ACIVICIN) (an inhibitor of gamma glutamyl transpeptidase). Cytotoxicity of OTA on OK cells was evaluated by applying the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. None of the listed agents diminished OTA cytotoxicity significantly; ACIVICIN even increases OTA cytotoxicity. In contrast, analysis of the HPLC profiles of OTA metabolites produced during these incubations indicated that the pattern, the quantity of metabolites, and the nature of the derivatives were modulated by these agents. Ochratoxin B (OTB), open-ring ochratoxin A (OP-OA), 4 hydroxylated OTA, 10 hydroxylated OTA, OTA without phenylalanine, OTB without phenylalanine, and a dechlorinated OTA metabolite could be identified by nano-ESI-IT-MS.

Acetylcysteine↗

PubMed2006

Advantages and drawbacks of immunoaffinity columns in analysis of mycotoxins in food.

A number of countries are setting legislations on mycotoxins. In order to reduce dispute between importing and exporting countries, the analytical data should be as comparable as possible, especially when levels are close to the regulatory limits. The present trend in the analysis of mycotoxins is to use immunoaffinity column (IAC) as a clean-up and enrichment technique, and Association of Official Analytical Chemists and European Union have validated methods which address a few food commodities. This study describes our experience using both conventional and IAC approaches in the analysis of three mycotoxins. Aflatoxins (AFs): Aflatoxin G1 has been detected by liquid-liquid partitioning methods with HPLC detection as false-positive in some maize. On IACs, this compound behaves as an AF, lowering the amount of the AFs trapped. The problem was solved using either TLC or HPLC with detection in the Kobra cell. Depending on the additives to food during the processing and cooking, the AFs might appear as an opened ring not recognised by the antibody. Fumonisins (FB): Compounds interfering with the FB's antibodies were also observed while analysing breakfast cereals leading to underestimation of FB. Ochratoxin A (OTA): Depending on the food composition and extraction techniques, OTA is underestimated with IAC in some breakfast cereals and coffee. These data strengthen the necessity to validate methods using IAC for each complex matrix.

Aflatoxin B1↗

PubMed2004

Ochratoxin study.

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Administration, Oral↗

PubMed2004

Analysis of ochratoxin A in foods consumed by inhabitants from an area with balkan endemic nephropathy: a 1 month follow-up study.

In the 1950s, a series of publications from Bulgaria, Yugoslavia, and Romania locally described a kidney disease called Balkan Endemic Nephropathy (BEN). In Bulgaria, the exposure of populations to ochratoxin A (OTA) was supported by analysis of individual food items demonstrating a higher prevalence and higher levels of OTA in food from the high-incidence areas of BEN. In this work, food consumption from a series of individuals from two villages of the BEN area during 1 month was followed using the duplicate diet method. Meals consumed by volunteers from both villages showed uneven OTA contents, spreading from below the limit of quantification (<0.07 microg/kg) to 2.6 microg/kg. The average weekly intake of OTA varies from 1.86 to 92.7 ng/kg of body weight. Some of these levels approach the provisional tolerable weekly intake (PTWI) established by the JECFA at 100 ng/kg of body weight. These results confirm previous studies performed in the same area and demonstrate the high exposure of this population to OTA, thus strengthening the hypothesis of the involvement of this mycotoxin in BEN etiology.

Adult↗

PubMed2004

Evidence for covalent DNA adduction by ochratoxin A following chronic exposure to rat and subacute exposure to pig.

Ochratoxin A (OTA) is a nephrotoxic mycotoxin that is a potent renal carcinogen in male rats and is suspected of being the etiological agent of Balkan endemic nephropathy (BEN) and its associated urinary tract cancers. Conflicting results have been obtained regarding the genotoxicity of OTA and its ability to react directly with DNA upon oxidative bioactivation to yield covalent DNA adducts. To characterize DNA adduction by OTA, the present study utilizes the photooxidative properties of the toxin to generate authentic C8 OTA-3'-monophosphate-deoxyguanosine (3'-dGMP) adducts for use as cochromatographic standards for (32)P-postlabeling detection of OTA-mediated DNA adduction in the kidney of rat and pig. Our results show evidence for the photooxidation of OTA to yield carbon (C)- and oxygen (O)-bonded C8-3'-dGMP adducts (C-C8 and O-C8) that have been isolated and characterized by LC/MS with in-line UV and electrospray negative ionization (ES(-)) detection. A comparison to previously published work on related C8-dG adducts supports C8 attachment by OTA. The C-C8 OTA-3'-dGMP adduct standard is shown by (32)P-postlabeling to comigrate with the major lesion detected in the kidney of rat following chronic exposure to OTA and with one of four adducts detected in the kidney of pig following subacute exposure to the toxin. The O-C8 OTA-3'-dGMP adduct standard is also shown to coelute with a lesion detected in rat kidney. These findings suggest a role for the OTA phenoxyl radical in OTA-mediated DNA adduction in vivo, provide a rationale for the tumorigenesis of OTA, and strengthen the OTA hypothesis in the etiology of BEN and the associated urinary tract tumors.

Animals↗