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Biomedical subjects

J L Benoit-Guyod

Publications and source records attributed to J L Benoit-Guyod.

31 records · Page 2Linked to original sources

Orellanine inhibits protein synthesis in Madin-Darby canine kidney cells, in rat liver mitochondria, and in vitro: indication for its activation prior to in vitro inhibition.

Pure orellanine, a nephrotoxic compound extracted from the mushroom Cortinarius orellanus, which is known to induce severe kidney damage several days or weeks after ingestion, is found to inhibit strongly the synthesis of macromolecules (proteins, RNA and DNA) in Madin-Darby canine kidney (MDCK) cells and in rat liver mitochondria, although the uptake of labelled precursors of the above macromolecules is not significantly altered. Direct addition of orellanine to a cell-free system of rabbit reticulocyte lysate does not produce any inhibition of protein synthesis. However, when orellanine is pre-incubated with activating rat liver microsomal systems, this inhibition occurs. Thus, the in vivo inhibition of protein synthesis is most likely due to a metabolite of orellanine.

2,2'-Dipyridyl↗

Biodegradation potential of some micromycetes for pentachlorophenol.

A first screening was performed upon 100 strains of micromycetes cultivated on solid media (malt extract medium and mineral medium) with pentachlorophenol (PCP) (0.5 g/liter). Under these conditions, 50 strains gave a light blurring around the inoculation spot, indicating some PCP degradation. Later, 50 selected strains were cultivated in liquid synthetic medium with PCP (1 g/liter). After 6 days of cultivation, photodegradation occurred for 25%. On the whole, the consumption of PCP was 25% for Zygomycetes, 3% for yeasts, and 10-15% for Deuteromycetes, except 7% for Tuberculariales. It was shown that glucose repressed the PCP consumption. Among degrading fungi, some could grow with PCP when cultures were initiated with spores, others could not. A more detailed study was done with Phoma glomerata cultivated in liquid synthetic medium (PCP 100 mg/liter) in darkness or with light. Photodegradation increased up to 25% but abiotic degradation occurred also in darkness (8%). Consumption of PCP by Ph. glomerata was 27% after 2 days with light and was lower in darkness (19%).

Biodegradation, Environmental↗

Environmental and health risks of hydroquinone.

Hazard assessment of hydroquinone has been evaluated from bibliographical and original data on the physicochemical properties, the environmental behavior, and the biological effects of this aromatic compound. Hydroquinone, which is produced in large amounts and widely used, must be considered as an environmental contaminant. However, it is not persistent. The ecotoxicity of this molecule, which must be linked to its physicochemical properties, varies from species to species. Its acute and chronic toxicity toward higher terrestrial organisms is moderate. Hydroquinone is estimated to be nonmutagenic by the Ames test but induces chromosome aberrations or karyotypic effects in eucaryotic cells. Carcinogenic and teratogenic potentials have been at present inadequately studied. The study underlines the complementarity of QSAR models and experimental approaches when an attempt is made to obtain ecotoxicological profiles of pollutants.

Animals↗

Metabolism of ferulic and syringic acids by micromycetes.

The ability of 814 strains of Micromycetes to grow on ferulic and syringic acids was investigated. After cultivation on solid media, 106 and 108 strains were selected and cultivated in liquid synthetic medium. Chromatographic analysis allowed classification of fungi into different groups according to the consumption of phenolic compounds and the appearance of new metabolites. Finally, Paecilomyces variotii and Pestalotia palmarum were chosen and cultivated in the presence of ferulic acid in two different culture media. These two Fungi Imperfecti were able to consume the phenolic compound rapidly and completely.

Anticoagulants↗

Effects of chlorophenols on isolated class A chloroplasts and thylakoids: a QSAR study.

A series of 22 chlorinated phenols was studied for their effects on photosynthesis of isolated chloroplasts. Each chlorophenol was an uncoupler, but the uncoupling activity depended upon substitution. The di-, tri-, or pentachloro substitution greatly enhanced the uncoupling activity. However, 2,6 substitution was not favorable to the uncoupling activity. Fifty percent uncoupling of photophosphorylations was obtained for concentrations between 4 mM for phenol itself, and 20 microM for pentachlorophenol. The quantitative structure-activity relationship (QSAR) study indicated a good relationship between, on the one hand, steric and electronic parameters, and, on the other hand, the uncoupling activity. In such equations, the A parameter describing ortho-substitution, always presented a negative sign. No good equation could be obtained with only log P and sigma. At concentrations which generally induced uncoupling, the chlorinated phenols inhibited the electron transfer in thylakoids. Di, tri, or penta substitution by chlorine enhanced the inhibition. A good relation appeared between this effect and the steric parameters MR and A. The study of isolated class A chloroplasts demonstrated that the uncoupling and the inhibition of the electron transfer in thylakoids could explain the effect of the chlorophenols on the whole photosynthetic mechanism. The effects of phenols on isolated chloroplasts were compared to those obtained with the same series on mitochondria. To explain the differences between QSAR equations, on the one hand for chloroplasts, and, on the other hand, for mitochondria, we suggested a selective binding of chlorinated phenols to proteins of the biological membranes.

Chlorophenols↗

A quantitative structure-activity relationship study on substituted pyridines as a contribution to the knowledge of the toxic effects of orellanine, a toxin from the mushroom Cortinarius orellanus.

Quantitative structure-activity relationships are established based upon the toxicity of 21 substituted pyridines. They are used as a predictive tool to calculate the toxicity of orellanine, a toxin from the mushroom Cortinarius orellanus (Fries). The actual toxicity of orellanine is quite different from the values calculated based upon the postulated bipyridine structure. The exact structure of orellanine may be questioned. However, our results show that even slight variations of the substituents of pyridines may cause dramatic changes of toxicity.

2,2'-Dipyridyl↗

Effect of chlorophenols on isolated plant mitochondria activities: a QSAR study.

Twenty-three chlorinated monophenols were investigated for their uncoupling and inhibitory properties on plant mitochondria. All the studied compounds had uncoupling properties but their activity was submitted to quantitative changes from 1- to 400-fold, according to the substitution. They also had inhibitory properties on the electron transfer at a level located upstream to the quinone pool. Three inhibitory types could be recognized: (a) chlorophenols inhibiting similarly the oxidation of every type of substrate (NADH, succinate, alpha-ketoglutarate, at pH 7.2; malate, at pH 7.5), (b) chlorophenols inhibiting first complex I, and (c) chlorophenols inhibiting first complex II. In this last case, the presence of substituents at the 2 and 6 positions increases selectively the inhibition of succinate oxidation. A quantitative structure activity relationship (QSAR) study was undertaken and showed that a good correlation appeared between the steric parameter, 1 chi v, and the inhibitory properties with NADH as substrate. This result could be explained by the binding of the chlorinated phenols with NADH dehydrogenase whose position, on the external surface of the mitochondrial membrane, is favorable to good accessibility of the xenobiotic. Equations for inhibitory properties with other substrates were clearly different. The relation between the uncoupling activity and the studied parameters was more complex but a good correlation occurred with the steric parameter (sigma D, A) and the electronic parameter sigma. Neither log P nor sigma alone gave equations of good quality. These results suggest a competition between the chlorophenol mobility in the inner membrane, necessary for uncoupling, and binding with different proteins in the same membrane on which the inhibitory activity is dependent.

Cell-Free System↗

Toxicity and QSAR of chlorophenols on Lebistes reticulatus.

The 24-h toxicity of 20 substituted chlorophenols upon Lebistes reticulatus has been determined. The biological results have been tentatively connected with several of the following six parameters: logarithm of the octanol-water partition coefficient (log P); index of molecular connectivity (1 chi v); molecular refraction (RM); perimeter of the efficient section of the molecule (sigma D); constants of HAMMET (sigma); and melting point (F). A correlation is achieved using sigma D and sigma D2 with a correlation coefficient of 0.943.

Animals↗

GABA transaminase inhibitors.

In summary, several branched-chain fatty acids appeared to be competitive inhibitors of GABA-T and non-competitive inhibitors of SSADH. These compounds produce an increase in brain GABA level, and for two of these it was shown that the increase differs among various brain areas. An increase of GABA cannot be obtained by inhibition of SSADH. The increase in brain GABA seems to correlate with the anticonvulsant activity of branched-chain fatty acids.

4-Aminobutyrate Transaminase↗