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Biomedical subjects

M Genty

Publications and source records attributed to M Genty.

9 recordsLinked to original sources
PubMed2001

Determination of the passive absorption through the rat intestine using chromatographic indices and molar volume.

Immobilized artificial membrane (IAM) chromatography coupled to physicochemical descriptors was evaluated to model the passive intestinal absorption of drugs through rat gut sacs. The chromatographic capacity factors (logk'(IAM)) of 12 structurally diverse compounds were determined on a IAM PC DD2 column. The passive permeabilities (P(a)) of the drugs were determined through rat everted gut sacs or through non-everted sacs for actively transported molecules. Correlation studies between logk'(IAM), physicochemical descriptors and P(a) were conducted by stepwise multiple linear regression (MLR) and back-propagation neural network (BPNN). MLR and BPNN showed that logk'(IAM) was the descriptor which correlated best with P(a). Considering the molar volume as an additional descriptor, the correlation was improved. Retention indices on IAM and the molar volume can be used concurrently to predict passive drug absorption.

Algorithms↗
PubMed2001

Kinetic parameters of hepatic oxidation of cyclic fatty acid monomers formed from linoleic and linolenic acids.

Cyclic fatty acid monomers (CFAM) occur from linoleic (CFAM-18:2) or linolenic (CFAM-18:3) acids present in some edible oils as a result of domestic frying or industrial refining. They present adverse effects in pups and weaning rats. In the present work, we studied the importance of hepatic oxidation in the metabolism of CFAM. For this purpose, kinetic parameters of Carnitine Palmitoyl Transferase I (key enzyme of the channeling of the fatty acids into the mitochondrial beta-oxidation pathway) and Acyl CoA Oxidase (key enzyme of the peroxisomal oxidation pathway) towards CFAM-18:2 and CFAM-18:3 were calculated on hepatic sub-cellular fractions of rats. For mitochondrial oxidation of CFAM, we observed a lower oxygen consumption and a lower activity of Carnitine Palmitoyl Transferase compared to 18:2w6 and 16:0. For peroxisomal oxidation, CFAM-18:2 showed the same kinetic parameters (Vm and K(0.5)) as 18:2w6 and 16:0, used for oxidative controls, whereas CFAM-18:3 presented a lower Vm (-50%). This difference should induce a lower catabolism of CFAM-18:3 in liver. This could contribute to their accumulation and probably to their toxic effect.

Journal Article↗
PubMed2000

Effects of conjugated linoleic acid isomers on lipid-metabolizing enzymes in male rats.

Male weanling Wistar rats (n = 15), weighing 200-220 g, were allocated for 6 wk to diets containing 1% (by weight) of conjugated linoleic acid (CLA), either as the 9c,11 t-isomer, the 10t,12c-isomer, or as a mixture containing 45% of each of these isomers. The five rats of the control group received 1% of oleic acid instead. Selected enzyme activities were determined in different tissues after cellular subfractionation. None of the CLA-diet induced a hepatic peroxisome-proliferation response, as evidenced by a lack of change in the activity of some characteristic enzymes [i.e., acyl-CoA oxidase, CYP4A1, but also carnitine palmitoyltransferase-I (CPT-I)] or enzyme affected by peroxisome-proliferators (glutathione S-transferase). In addition to the liver, the activity of the rate-limiting beta-oxidation enzyme in mitochondria, CPT-I, did not change either in skeletal muscle or in heart. Conversely, its activity increased more than 30% in the control value in epididymal adipose tissue of the animals fed the CLA-diets containing the 10t,12c-isomer. Conversely, the activity of phosphatidate phosphohydrolase, a rate-limiting enzyme in glycerolipid neosynthesis, remained unchanged in adipose tissue. Kinetic studies conducted on hepatic CPT-I and peroxisomal acyl-CoA oxidase with CoA derivatives predicted a different channeling of CLA isomers through the mitochondrial or the peroxisomal oxidation pathways. In conclusion, the 10t,12c-CLA isomer seems to be more efficiently utilized by the cells than its 9c,11t homolog, though the Wistar rat species appeared to be poorly responsive to CLA diets for the effects measured.

Acyl-CoA Oxidase↗
PubMed2000

Incorporation and metabolism of trans 20:5 in endothelial cells. Effect on prostacyclin synthesis.

To study the ability of long-chain trans fatty acids (FA) to be incorporated and metabolized into endothelial cells, bovine aortic endothelial cells were incubated with medium enriched eicosapentaenoic acid (EPA) bound to albumin (M2) or one of its geometrical isomers: 20:5 5c,8c,11t,14c,17c (M3), 20:5 5c,8c,11c,14c,17t (M4), or 20:5 5c,8c,11t,14c,17t (M5). After 48 h of incubation, supernatant and cells were harvested and their lipids were analyzed, including prostacyclin synthesis. EPA and 22:5n-3 of endothelial cells incubated with M2 were, respectively, three and two times higher than in control cells (incubated in M1, without any fatty acid added), whereas 22:6n-3 increased only in the supernatant, suggesting its release after biosynthesis. However, 18:2n-6 and 22:4n-6 decreased (about 30%). Trans 20:5 isomers represented 4.7, 3.9, and 5.2% of total phospholipid FA in endothelial cells incubated with M3, M4, and M5, respectively. They were elongated into trans 22:5 and trans 24:5, as revealed by gas chromatography-mass spectrometry and gas chromatography-Fourier transform infrared analysis. In cells incubated with M2, M3, M4, and M5, prostacyclin synthesis was inhibited by 49.0, 62.5, 60.5, and 72.0%, respectively. This effect may be due to less available arachidonic acid in the cells and to a competition between EPA isomers and AA at the level of cyclooxygenase pathway, as it was demonstrated that 20:5 delta17t was metabolized by this enzyme.

Animals↗
PubMed2000

Cyclic fatty acid monomers from heated oil modify the activities of lipid synthesizing and oxidizing enzymes in rat liver.

Cyclic fatty acid monomers purified from a heated linseed oil were given for 2 wk to adult rats as triacylglycerol at two dose levels, i.e., 0.1 and 1 g/100 g diet, to determine their effect on some aspects of lipid metabolism. Indirect evidence of a peroxisome proliferator-like effect was observed, as determined by an elevation of some characteristic enzyme activities, such as peroxisomal acyl-CoA oxidase, and the microsomal omega- but also (omega-1)-laurate hydroxylase (CYP4A1 and CYP2E1, respectively). The dietary cyclic fatty acids induced a coordinated regulation between the activities of the lipogenic enzymes studied (Delta9-desaturase, phosphatidate phosphohydrolase) and peroxisomal oxidation, but not with mitochondrial beta-oxidation. The dose-dependent decrease of Delta9-desaturase activity (P < 0.05) with cyclic fatty acid monomer intake was accompanied by a similar decrease of the monounsaturated fatty acid level in liver. The increase in the gamma-linolenic acid level also suggested an increase in Delta6-desaturase activity with cyclic fatty acid intake (P < 0.05). In addition, our results strongly suggested that the altered liver levels of eicosapentaenoic and arachidonic acids were due to the peroxisomal retroconversion process in rats fed cyclic acids. Finally, an effect of these cyclic compounds on the carbohydrate metabolism cannot be disregarded because they decreased liver glycogen concentration. We conclude that cyclic fatty acid monomers affect different aspects of lipid metabolism, including a phenotypic peroxisome proliferator response. This provides the ground for further studies investigating the biochemical pathways that underlie the nutritional effect of such molecules.

Acyl-CoA Oxidase↗