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A López de Cerain

Publications and source records attributed to A López de Cerain.

11 recordsLinked to original sources
PubMed2006

Phenazine 5,10-dioxide derivatives as hypoxic selective cytotoxins: Part II. Structure-activity relationship studies.

The synthesis and evaluation as hypoxic selective cytotoxins of new derivatives of 2-amino or 2-hydroxyphenazine 5,10-dioxide are described. The compounds were developed as structural analogs of other bioreductive compounds and its in vitro cytotoxicities on V79 cells under hypoxic and aerobic conditions were determined. To gain insight into its mechanism of action electrochemical behavior, interaction with DNA experiments and QSAR studies were performed.

Animals↗
PubMed2005

Occurrence of ochratoxin A in cocoa beans: effect of shelling.

The aim of this study was to investigate the influence of the shelling process on the presence of ochratoxin A (OTA) in cocoa samples. Twenty-two cocoa samples were analysed for the determination of OTA before (cocoa bean) and after undergoing manual shelling process (cocoa nib). In order to determine OTA contamination in cocoa samples, a validated high-performance liquid chromatography (HPLC) method with fluorescence detection was used for the quantitative analysis of ochratoxin A (OTA). In both types of samples, OTA was extracted with methanol-3% sodium hydrogen carbonate solution and then purified using immunoaffinity columns prior to HPLC analysis. Due to the fact that different recovery values were obtained for OTA from both types of samples, a revalidation of the method in the case of cocoa nibs was needed. Revalidation was based on the following criteria: Selectivity, limits of detection and quantification (0.03 and 0.1 microg kg(-1), respectively), precision (within-day and between-day variability) and recovery 84.2% (RSD = 7.1%), and uncertainty (30%). Fourteen of the twenty-two cocoa bean samples (64%) suffered a loss of OTA of more than 95% due to shelling, six samples suffered a loss of OTA in the range 65-95%, and only one sample presented a reduction of less than 50%. The principal conclusion derived from this study is that OTA contamination in cocoa beans is concentrated in the shell; therefore, improvements of the industrial shelling process could prevent OTA occurrence in cocoa final products.

Cacao↗
PubMed2005

Alterations induced in vitro by ochratoxin A in rat lymphoid cells.

Ochratoxin A (OTA) is a nephrotoxic mycotoxin produced by species of the genus Penicillium and Aspergillus that is present in food and feed as a natural contaminant. It modifies the immune function in animals and inhibits the proliferative response of lymphocytes in vitro. The toxic effect of OTA (0.5, 2, 20 microM) in lympho-proliferative response, natural killer (NK) cell activity, cytotoxic T lymphocytes (CTL) activity and macrophages' bacteriolytic capability was studied in vitro after 1 hour of treatment. The proliferative response of lymphocytes to concanavalin A and lipopolysaccharide was not affected by OTA; the cytotoxic activity of NK cells was dose-dependent decreased; the CTL activity was significantly decreased at the lowest concentration; the bacteriolytic activity of macrophages varied only slightly. These in vitro results reproduced, at least in part, some effects detected previously in vivo. The protein synthesis inhibition and the oxidative metabolism of OTA coupled to the prostaglandin synthesis are probably implicated in NK cells' toxicity, because the effects were reverted by the addition of phenylalanine or piroxicam to the culture medium. The induction of apoptosis seems to be the principal mechanism of action in the CTL effect. The intracellular concentration of OTA after 1 hour was analysed by HPLC and was found to be proportional to the quantity of OTA added to the culture medium for the three cell types; the presence of phenylalanine and piroxicam on the culture medium did not change the intracellular OTA concentration.

Animals↗
PubMed2004

Determination of ochratoxin A in wine using liquid-phase microextraction combined with liquid chromatography with fluorescence detection.

A liquid-liquid microextraction technique (LPME) has been applied to the extraction of ochratoxin A (OTA) from wine prior to its quantification by HPLC-fluorescence detection. OTA was extracted from wine, through 1-octanol immobilized in the pores of a porous hollow fiber, and introduced into 1-octanol inside the fiber. Recovery was 77%. The method was adequate for quantification of OTA in wine at levels within the range 0.25-10 ng/ml with a LOD of 0.2 ng/ml, and can be a simple and inexpensive alternative to the use of inmunoaffinity columns in order to quantify OTA levels in wine.

Chromatography, High Pressure Liquid↗
PubMed2004

Immunotoxic effects of Ochratoxin A in Wistar rats after oral administration.

Ochratoxin A (OTA) is a mycotoxin produced by species of the genus Aspergillus and Penicillium. Human exposure has been demonstrated worldwide and its origin seems to be the intake of contaminated foods. The kidneys are the target organ of this mycotoxin. Immunotoxic and genotoxic effects of OTA were investigated in Wistar male rats (aged 12 weeks), treated by gavage with 50, 150 or 450 microg OTA/kg body weight for 28 days, in the context of a general toxicity study, which was designed following the recommendations of OECD guideline 407. At the end of the study, the mean plasma concentration of the mycotoxin was determined, several immune function assays were performed and bone marrow smears were obtained and stained in order to analyse micronuclei in polychromatic erytrocytes. Mean plasma concentration was found to be 187, 600 and 807 microg/L, respectively. At the highest dose, a decrease in body weight gain was observed. Histopathological investigations revealed tubulonephrosis and acute tubular necrosis in the kidneys of the animals treated with OTA. The frequency and severity of the lesions increased with the dose. The response of splenocytes to sheep red blood cells was decreased in a dose-dependent manner; however, nonstatistically significant differences were obtained. The natural killer cell activity was strongly affected by OTA treatment. Cytotoxic T lymphocyte activity was lower in the animals exposed to 50 microg OTA/kg b.w. but was not modified in the groups exposed to 150 and 450 microg OTA/ kg b.w. The bacteriolytic capability of macrophages was significantly reduced in groups exposed to 50 and 450 microg OTA/ kg b.w. The number of micronuclei in bone marrow polychromatic erytrocytes did not vary significantly with respect to the control at any dose, but a false negative result can not be ruled out because the exposure doses were much lower than those recommended in OECD guideline 474.

Administration, Oral↗
PubMed2004

Validation of a high-performance liquid chromatography analytical method for ochratoxin A quantification in cocoa beans.

A validated high-performance liquid chromatography (HPLC) method with fluorescence detection for the quantitative analysis of ochratoxin A (OTA) in cocoa beans is described. OTA was extracted with methanol-3% sodium hydrogen carbonate solution and then purified with immunoaffinity columns before its analysis by HPLC. The validation of the analytical method was based on the following criteria: selectivity, linearity, limit of detection and quantification, precision (within- and between-day variability) and recovery, robustness and uncertainty. Detection and quantification limits were 0.04 and 0.1 mug kg(-1), respectively. Recovery was 88.9% (relative standard deviation = 4.0%). This method was successfully applied to the measurement of 46 cocoa bean samples of different origins. A total of 63% of cocoa bean samples was contaminated with a level greater than the limit of detection. The means and medians obtained for cocoa bean were 1.71 and 1.12 mug kg(-1), respectively. Surveillance controls should be set up in both crops and factories involved in transformation processes to avoid this mycotoxin in final products.

Cacao↗
PubMed2001

Determination of ochratoxin A in pig liver-derived pâtés by high-performance liquid chromatography.

A solid phase extraction procedure followed by HPLC analysis with fluorescence detection has been developed for ochratoxin A (OTA) in pâtés derived from pig liver. After a previous extraction of OTA with 60% acetonitrile, all the samples were purified through C8 columns. The percentage recovery was 85.7% and the lower limits calculated for accurate detection and quantitation were 0.56 ng/g and 0.84 ng/g respectively. The HPLC procedure showed a good linearity in the interval of equivalent OTA concentrations of 0.84 to 3 ng/g. Values <10% were obtained for precision in HPLC determinations performed (n = 3) and (n = 9). Stability of calibration standards and samples during the analytical procedure was also demonstrated. This method was successfully applied to 38 pig-derived pâtés and three samples were found to be positive with OTA levels above the detection limit. The highest concentration (1.77 ng/g) has been found in a home-made pâté.

Animals↗
PubMed1999

Carbonyl reductase and NADPH cytochrome P450 reductase activities in human tumoral versus normal tissues.

The use of bioreductive agents in enzyme-directed bioreductive therapy has been proposed to take advantage not only of hypoxia in tumours, but also of the presence of reductases that metabolise such compounds. In this study, we studied the activities of NADPH cytochrome P450 reductase (P450R) and carbonyl reductase (CR) in 17 human lung tumours and 18 human breast tumours, together with the corresponding normal tissues. For lung cancer but not for breast cancer there was a significant difference in the CR activity between normal and tumour tissue. CR activity was increased with respect to the normal tissue between 2-fold and 40-fold indicating heterogeneity in tumour samples. No relationship was found between CR activity and the histological type, tumoral grade or TNM stage of the tumours. Although some variation in P450R activity in tumoral versus normal tissues was found in the majority of the samples studied, no significant differences could be demonstrated.

Alcohol Oxidoreductases↗
PubMed1997

DT-diaphorase and cytochrome B5 reductase in human lung and breast tumours.

The level of expression of enzymes that can activate or detoxify bioreductive agents within tumours has emerged as an important feature in the development of these anti-tumour compounds. The levels of two such reductase enzymes have been determined in 19 human non-small-cell lung tumours and 20 human breast tumours, together with the corresponding normal tissue. DT-diaphorase (DTD) enzyme levels (both expression and activity) were determined in these samples. Cytochrome b5 reductase (Cytb5R) activity was also assessed. With the exception of six patients, the levels of DTD activity were below 45 nmol min(-1) mg(-1) in the normal tissues assayed. DTD tumour activity was extremely variable, distinguishing two different groups of patients, one with DTD activity above 79 nmol min(-1) mg(-1) and the other with levels that were in the same range as found for the normal tissues. In 53% of the lung tumour samples, DTD activity was increased with respect to the normal tissue by a factor of 2.4-90.3 (range 79-965 nmol min[-1] mg[-1]). In 70% of the breast tumour samples, DTD activity was over 80 nmol min(-1) mg(-1) (range 83-267 nmol min[-1] mg[-1]). DTD expression measured by Western blot correlated well with the enzyme activity measured in both tumour and normal tissues. The levels of the other reductase enzyme, Cytb5R, were not as variable as those for DTD, being in the same range in both tumour and normal tissue or slightly higher in the normal tissues. The heterogeneous nature of DTD activity and expression reinforces the need to measure enzyme levels in individual patients before therapy with DTD-activated bioreductive drugs.

Aged↗
PubMedDate not supplied

[Characteristics and value of chromosome aberrations induced by antitumor treatments in pediatric patients with cancer].

Cytogenetic studies were performed on 80 pediatric cancer patients to test the chromosomal damage induced by the chemotherapy treatments. G-banded karyotypes were performed on peripheral blood lymphocytes (PBL) (n = 127) obtained at diagnosis, during treatment, at remission and at relapse. We detected a significant increase in the number of altered karyotypes in the samples during treatment, lowering to similar values to those at diagnosis at two-year remission. Most of the chromosomal aberrations (CA) detected during chemotherapy were unbalanced (75%) and affected most frequently chromosomes 1, 3, 5, 6, 11, 12, 16 and 17. There was also a marked increase of CA in samples at relapse, with similar features (type and distribution) to those detected during treatment. There was an outstanding correlation between the chromosomal breakpoints in our series and fragile sites (58%), oncogene (75%) and tumour suppressor gene (33%) loci described in the literature. The results obtained suggest that the cytostatic drugs induce a transient increase in chromosome fragility that focuses to several cancer-associated breakpoints.

Antineoplastic Agents↗