Recherche de nouveaux chélateurs du manganèse en vue de la détoxication de l'organisme (Études in vivo et in vitro chez le rat)

METZ-SCD (574632105) / SudocSudocFranceF

Immobilisation in vitro du plomb par l'apatie. (Influence sur la biodisponibilité de ce métal chez le rat)

METZ-SCD (574632105) / SudocSudocFranceF

EFFET D'UNE INTOXICATION IP DE AlCb CHEZ LE RAT JEUNE ET ADULTE : ALUMINEMIE, ELIMINATION URINAIRE ET ACTIVITE DE LA CHOLINEACETYLTRANSFERASE CEREBRALE

Adult male rats and 13 days old rats received one IP injection of aluminum chloride (20 and 40 mg/kg). At the dose of 20 mg Al chloride, after 9 days, the Al plasma concentrations decrease in young rats and adult rats: 57.9 and 42.8% respectively. During the same period, at 40 mg Al/kg, the Al concentration decrease significantly: 30.9 arid 12.5% respectively. At this dose, after 48 h, the aluminum concentration and the cholineacetyltransferase activity in cerebral homogenates did not differ in comparison to the controlDes rats mâles adultes et des rats âgés de 13 jours reçoivent une injection unique de chlorure d'Al administré par voie IP aux doses de 20 et 40 mg Al/kg. A la dose de 20 mg Al/kg, au bout de 9 jours, l'aluminémie a diminué de 57,9% chez le jeune et de 42,8% chez l'adulte, comparativement au jour 1. A la dose de 40 mg Al/kg, les diminutions sont respectivement de 30,9% et 12,5% pendant la même période; toutefois au bout de 48 h après l'injection, l'aluminium ne s'est pas accumulé dans le cerveau et l'activité de la cholineacétyltransférase cérébrale n'est pas modifiée, qu'il s'agisse du rat âgé de 13 jours ou du rat adult

The effects of aluminum, iron, chromium, and yttrium on rat intestinal smooth muscle in vitro

International audienc

Environmental boron exposure and activity of delta-aminolevulinic acid dehydratase (ALA-D) in a newborn population.

Following boron intake, multiple effects have been observed in animal experiments. However, human data is lacking, and no data is available on the ability of boron to accumulate in fetal tissues. Positive responses in animal species suggest that developmental toxicity may be an area of concern in humans, following exposure to boron. Two hypotheses have seemed to account for the multiple effects described in scientific findings. One hypothesis is that boron is a negative regulator that influences a number of metabolic pathways by competitively inhibiting some key enzyme reactions. The other hypothesis is that boron has a role in ionic membrane transport regulations. To better understand boron potential toxicity, the present study examined the relationship between boron exposure and some key enzymes, well-known for their affinity for mineral elements, such as delta-aminolevulinic acid dehydratase (ALA-D), and two fundamental enzymes having a role in ionic membrane transport regulations (Ca-pump and Na(+)K(+)-ATPase). We investigated the potential effects of an environmental boron exposure on the activity of these enzymes in an urban population of 197 "normal" newborns. Environmental boron exposure was assessed in placental tissue. Because of the well-known inhibiting effect of lead on these enzymes, cord blood and placental lead were also analyzed. After adjustment for potential confounders, including lead, placental boron levels were negatively significantly correlated to ALA-D activity while Ca-pump and Na(+)K(+)-ATPase activities did not seem to be affected by the level of boron exposure. Given boron's ability, as a Lewis acid, to complex with hydroxyl groups, we suggest that such a mechanism would explain the inhibiting effect of boron on ALA-D

Genotoxic and CYP 1A enzyme effects consecutive to the food transfer of oil spill contaminants from mussels to mammals

The transfer of polycyclic aromatic hydrocarbons (PAHs) from bivalves, through the food chain to vertebrates was of concern. Our research aimed at estimating potential effects for consumers resulting from the ingestion of seafood contaminated by oil spill pollutants. After the “Erika” wreck, mussels (Mytilus sp.) were collected from sites of the Atlantic coast impacted to various degrees by the oil slick and constituted contaminated food for rats during 2 and 4 weeks. Genotoxic damage were studied in rats by means of COMET assay carried out in liver, bone marrow and peripheral blood. Biochemical and genomic effects such as the induction of CYP 1A1 and the expression of cytochrome genes were measured in rat livers. The most sensitive biological parameter reflecting the transfer of contaminants via the food appeared to be DNA breaks studied by means of the COMET assay. Genotoxic damage, observed mainly in the liver, were rather moderate and remained not persistent. This study underlined the bioavailability of pollutants in fuel oil contaminated mussels for consumers, and the complexity of the contamination consecutive to the oil spill. The occurrence of related PAH compounds in addition to non-substituted PAHs in fuel oils and mussels raised the question of their implication in the registered effects

Insights into the role of the metal binding site in methionine-R-sulfoxide reductases B

Methionine sulfoxide reductases B (MsrBs) catalyze the reduction of methionine-R-sulfoxide via a three-step chemical mechanism including a reductase step, formation of an intradisulfide bond followed by a thioredoxin recycling process. Fifty percent of the MsrBs, including the Escherichia coli enzyme, possess a metal binding site composed of two CXXC motifs of unknown function. It is located on the opposite side of the active site. The overexpressed E. coli MsrB tightly binds one atom of zinc/iron. Substitution of the cysteines of E. coli MsrB results in complete loss of bound metal and reductase activity, and leads to a low-structured conformation of the protein as shown by CD, fluorescence, and DSC experiments. Introduction of the two CXXC motifs in Neisseria meningitidis MsrB domain leads to a MsrB that tightly binds one atom of zinc/iron, shows a strongly increased thermal stability and displays a reductase activity similar to that of the wild-type but lacking thioredoxin recycling activity. These results demonstrate the stabilizing effect of the metal and the existence of a preformed metal binding site in the nonbound metal MsrB. The data also indicate that metal binding to N. meningitidis MsrB induces subtle structural modifications, which prevent formation of a competent binary complex between oxidized MsrB and reduced thioredoxin but not between reduced MsrB and substrate. The fact that the E. coli and the N. meningitidis MsrBs exhibit a similar thermal stability suggests the existence of other structural factors in the nonbound metal MsrBs that compensate the metal bound stabilizing effect