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G Jadot

Publications and source records attributed to G Jadot.

At least 19 recordsLinked to original sources
PubMed1996

Differences in hypolipidaemic effects of two statins on Hep G2 cells or human hepatocytes in primary culture.

1. The objective of this study was to compare in cultured human hepatocytes or Hep G2 cells, changes in the fate of unesterified low density lipoprotein (LDL)-cholesterol induced by crilvastatin, a new cholesterol lowering drug and a reference statin, simvastatin. 2. The experiments were carried out for 20 h, each well contained 4.2 x 10(5)/cm2 Hep G2 cells or 0.5 x 10(5)/Cm2 human hepatocytes, 130 microM ursodeoxycholate, 0.68 microCi or 1.59 microCi unesterified human [14C]-LDL-cholesterol, crilvastatin or simvastatin at 0 or 50 microM (both cell types) or 300 microM (Hep-G2 cells). Incubation with the two drugs resulted in increased amounts of unesterified [14C]-LDL-cholesterol taken by the two cell types, compared to control. 3. Crilvastatin 50 microM led to significantly higher quantities of [14C]-glyco-tauro-conjugated bile salts, compared to simvastatin. Statins reduced the apo B100 level secreted by the two cell types (simvastatin) or human hepatocytes (crilvastatin). Crilvastatin enhanced both the level of apo A1 secreted by the Hep G2 cells and the level of APF, a high density lipoprotein (HDL) and biliary apoprotein. 4. Crilvastatin not only acts by stimulating LDL-cholesterol uptake by hepatocytes, but also by enhancing the catabolism of LDL-cholesterol in bile salts and probably by stimulating HDL and/or bile component secretion. Such a mechanism was not previously described for HMG CoA reductase inhibitors. Our results on APF show that this apoprotein could be considered also as an indicator of changes in bile and/or HDL compartments. 5. The human hepatocyte model appeared to be a suitable and relevant model in the pharmacological-metabolic experiments carried out in this study. It led to more consistent data than those obtained with Hep G2 cells.

Adult↗
PubMed1995

Effect of crilvastatin, a new cholesterol lowering agent, on unesterified LDL-cholesterol metabolism into bile salts by rat isolated hepatocytes.

1. The aim of these experiments was to determine the effect of crilvastatin, a new cholesterol lowering agent, on the metabolism of unesterified low density lipoprotein (LDL)-cholesterol by rat freshly isolated hepatocytes. This preclinical model was developed as an alternative to in vivo experiments, to mimic the metabolic effects of a molecule on its target cells and to define optimal conditions for future experimentation on human hepatocytes. 2. Cells were obtained from normolipidaemic or hypercholesterolaemic rats, hypercholesterolaemia was nutritionally induced. Incubations were performed in a medium containing 600 microM taurocholate and 50 microM or 300 microM crilvastatin. 3. This molecule was shown in vitro to be carried by physiological transporters, i.e., albumin-bile salt micellar associations and LDL. Crilvastatin induced a significance increase in the synthesis and secretion by hepatocytes of bile salts resulting from the metabolism of unesterified LDL-cholesterol in both normolipidaemic and hypercholesterolaemic rats. Stimulation involved non-conjugated as well as tauro- and glyco-conjugated bile salts. These findings corroborate preliminary studies showing in vivo that crilvastatin enhances the secretion of bile acids by stimulating the uptake and incorporation of LDL-cholesterol by the liver.

Animals↗
PubMed1995

Clinical pharmacokinetics and delivery of bovine superoxide dismutase.

Experimentally, superoxide dismutase (SOD) protects against cytotoxological and histotoxological effects of superoxide anions, which play a fundamental role where inflammatory processes are involved. Currently, only bovine copper containing SOD (Cu-SOD) is available for clinical application in the treatment of patients with various arthritic diseases. The intramuscular route is the principal route to administer usual dosages of bovine Cu-SOD 4 to 32mg, 2 or 3 times weekly. A single dose corresponds to an optimal dose ranging from 30 to 200 micrograms/kg, determined from an established dose-response curve. After intramuscular injection of bovine Cu-SOD 8, 16 and 32mg the peak plasma concentration occurs 4 to 8 hours postdose and is 0.05, 0.16 and 0.39 mg/L, respectively. Clinically this metallo-protein is particularly effective for the treatment of inflammation and toxicity resulting from ionising irradiations, ischaemia and tumours. The major advantages of liposomally encapsulated bovine Cu-SOD are its improved pharmacokinetic characteristics, leading to a longer plasma half-life and a slower release of free bovine Cu-SOD. In humans, bovine Cu-SOD (free or liposomal), although a foreign protein, is well tolerated and produces no acute or delayed toxic effects.

Animals↗
PubMed1993

Effects of a subacute treatment in rats by a fresh cola extract on EEG and pharmacokinetics.

The compared effects of an acute and subacute treatment by fresh cola extract and caffeine on the caffeine pharmacokinetics and on cortical activities by spectral analysis of the electroencephalogram (EEG) are studied in rats. After acute cola administration, we observed an increase in half-life elimination of caffeine and a stabilization of its plasma/erythrocyte ratio. Chronic administration revealed differences in cola-caffeine penetration in erythrocytes and a reduction of the area under the curve (AUC) and plasma/erythrocyte ratio. We also noted a significant difference in the binding of the caffeine on plasma proteins after subacute administration of cola seed extract. Cola seed treatment induces an increase in the cortical activity with a widening of the dominant frequency spectrum 7- to 10-Hz band of EEG, whereas caffeine alone induces a shift of the dominant frequency band toward higher frequencies. The observed delay to obtain the greatest EEG effect related to the caffeine contained in cola seeds can be partially explained by the pharmacokinetic data.

Animals↗
PubMed1991

Oxygen-induced modifications of benzodiazepine receptors and D2 dopamine receptors in the rat under hyperoxia.

Peripheral-type benzodiazepine Receptors (PBR) in the kidney and Central-type Benzodiazepine Receptors (CBR) in the cerebral cortex were not affected in rats exposed to chronic hyperoxia (85% O2, ATA, 6 days). Nevertheless, cortical CBR showed a significant decrease (29%) after hyperbaric hyperoxia (100% O2, 3.5 ATA, 2 h) in rats at a preconvulsive stage, with no concomitant alteration of kidney PBR. A similar down-regulation of striatal D2 dopamine receptors was noticed (27%)--after hyperbaric hyperoxia--without any modification of cortical PBR. On the contrary, an up regulation of liver PBR was obtained in the same conditions (20%). It is likely that receptors implicated in neurotransmission are particularly down regulated or altered under hyperbaric hyperoxia.

Animals↗
PubMed1990

Anti-inflammatory activity of various superoxide dismutases on polyarthritis in the Lewis rat.

The anti-arthritic activity of four superoxide dismutases (SODs) has been compared by using the adjuvant-induced polyarthritis rat model. Many of the clinical signs observed in the rat closely resemble those of human rheumatic diseases and the Fiessinger-Leroy-Reiter syndrome. An original protocol and various approaches allowed study of the evolution of long term (30-90 days) SOD treatment. Results are relevant to clinical application: human and bovine Cu-SODs are fully active during secondary and tertiary arthritic reaction; homologous rat Cu-SOD is active only transiently at the end of the secondary reaction; human Mn-SOD is active only on the second stage of arthritic reaction. It should be noted that bovine and human SODs slightly delay the appearance of bony damage. These data were confirmed by the scintigraphic study. Finally it is noteworthy that drug pharmacological activity decreases when the blood level of anti-SOD antibodies increases. This indicates the existence of an immunological reaction following SOD administration.

Animals↗
PubMed1990

Normolipidaemic activity of liposomal-encapsulated superoxide dismutase in rats.

To determine the regulatory effects of superoxide dismutase (SOD) on lipid metabolism a simple model of hyperlipidaemia induced by a hypercholesterolaemic (HCT) diet in rat was used. In animals fed a HCT diet, triglyceride (TG) were increased by 126%, total cholesterol (TCT) by 40%, very low density lipoprotein (VLDL) by 124% and the TCT/HDL ratio by 82%. The procedure would therefore appear to model some of the risk factors of atherogenesis. In animals fed a hypercholesterolemic diet, liposomal Cu-SOD (200 micrograms/kg i.m. every two days; 1000 micrograms/kg i.m./day) decreased TG by 29 and 49%, TCT by 14 and 36%, TCT/HDL ratio by 32 and 60%, VLDL by 52 and 55% respectively and increased high density lipoprotein cholesterol (HDL-C) by 17 and 46% respectively. The present experiments show therefore that the administration of liposomal SOD has a marked effect on lipid parameters (particularly TCT and TG) and might therefore reduce the atherogenic risk by increasing HDL and decreasing VLDL and cholesterol atherogenicity ratio (CAR).

Animals↗
PubMed1989

Superoxide dismutase treatment reduces [3H]flunitrazepam affinity in cortex and hippocampus of the rat.

Superoxide dismutases (SOD) are essential enzymes involved in the cellular defense against oxidative processes occurring with the generation of the superoxide anion. In this work, we have investigated in the rat the effects of a subchronic administration of liposomal SOD from bovine erythrocytes, on benzodiazepine (BZD) 'central-type' receptor sites in cortex and hippocampus. Animals were treated for 15 days with an i.p. injection of liposomal SOD, and binding parameters were determined using [3H]flunitrazepam. BZD receptor affinity was found decreased, while no change was observed in the maximal binding capacity. With regard to previously reported data, our results show that the superoxide anion radical is involved in the modulation and/or the stability of 'central-type' BZD receptor sites.

Animals↗
PubMed1988

Treatment of brain trauma with liposomal superoxide dismutase.

Brain trauma was induced in rats by impact of a steel bar on the head with a force such that damage (as measured by neurological scoring) was reversible in fourteen days. Systemic treatment (intraperitoneal injections) with free bovine copper superoxide dismutase or a liposomal form of the enzyme considerably shortened recovery time to less than half. Tests included cranial nerves--cornean and aural reflexes, and sensorial motricity functions--gripping reflexes, displacement reactions, recovery and flexion reflexes, equilibrium tests and spontaneous mobility. Normalisation of EEG recordings was also greatly accelerated in the case of treated animals. No changes of brain glutathione peroxidase, glutathione transferase or Mn superoxide dismutase in traumatized animals were observed. However a slight decrease in Cu-SOD occurs. Cerebral lipoperoxidation is increased in the traumatized animals compared with controls. This increase is reduced on treatment of the rats with liposomal SOD (or the free enzyme). Very small amounts of the exogenous SOD pass the brain barrier, the permeability of which is increased in traumatized animals. The enzyme is particularly concentrated in the cortex. Despite apparent total neurological recovery at 15 days for untreated traumatized animals, significant differences in EEG recordings, in percentage cerebral water content and in histological examination of brain tissue of these controls compared with treated animals were observed with a net improvement in the latter case. The results obtained with this model suggest that clinical treatment of coma states and brain traumas with liposomal superoxide dismutase may have certain advantages over orthodox treatments.

Animals↗
PubMed1987

Behavioral effects resulting from sub-chronic treatment of rats with extract of fresh stabilized cola seeds.

The aim of our study was to compare the effects of a sub-chronic treatment with fresh cola seed extract and pure caffeine in the male rat. The activity tests (open-field) and reactivity (tail-tap, resistance to capture), show that fresh cola has an effect on behavior similar to that of caffeine. However, the effects of cola are more gradual than those of caffeine. Furthermore, cola administration leads to an increase in the fall latency observed during the grasping test. These results suggest that the fresh cola seed has both psychostimulating properties similar to those of caffeine, and an original effect on muscular tonus.

Animals↗
PubMed1987

Comparative anti-inflammatory activity of different superoxide dismutases and liposomal SOD in ischemia.

Comparison of superoxide dismutases from different sources with respect to biological activity in the rat tourniquet poditis model shows that anti-ischemic activity is very variable although all the enzymes have the same specific enzymic activity. Both bovine Cu-SOD and E. coli Mn-SOD have excellent properties whereas yeast Cu-SOD and the homologous rat Cu-SOD show zero activity. The results confirm earlier demonstrations that (1) "All superoxide dismutases are equal but some are more equal than others", (2) at the dose levels used (compatible with possible clinical use) homologous enzyme is inefficient and hence human Cu-SOD may not be effective in humans, (3) liposomal encapsulation of bovine Cu-SOD greatly enhances biological efficacity, provides a slow release mechanism of the enzyme and provides a powerful drug for the treatment of ischemic injury.

Animals↗
PubMed1986

[Neurochemical characteristics of opioid peptides].

Opioid peptides seem to be involved in an increasing number of cerebral functions. It appears from the most recent studies that these peptides are divided into three families: pro-opio-melanocortin, pro-enkephalin and prodynorphin. Unlike conventional neurotransmitters, these substances are fraught with extremely complex problems of specific biosynthesis and degradation. Finally, the multiplicity of opiate receptors and the search for specific endogenous or synthetic ligands raise major fundamental questions concerning the clinical relevance of studies performed on opioid peptides.

Aminopeptidases↗
PubMed1986

Antinociceptive action of picrotoxin in the mouse.

Picrotoxin, an antagonist of GABA-associated chloride ionophores with convulsant activity, possesses antinociceptive activity in the hot-plate and writhing tests in the mouse. Analgesia produced by a subconvulsant dose of picrotoxin (0.75 mg/kg, s.c.) was reversed by naloxone (1.0 mg/kg, s.c.), atropine (5 mg/kg, i.p.), and methysergide (10 mg/kg, i.p.) in the jumping reaction (hot-plate test). These data indicate that opiate pathways, as well as cholinergic and serotoninergic pathways could be involved in the mechanism that underlies picrotoxin-induced analgesia. Furthermore, such results should be considered when interpreting the behavioral effects of picrotoxin.

Analgesics↗
PubMed1986

Anti-inflammatory activity of superoxide dismutases: inhibition of carrageenan induced edema in rats.

Eighteen different superoxide dismutases from procaryote, plant, fish, bird and mammalian species have been tested for anti-inflammatory activity in the rat paw pad carrageenan-induced inflammation model. Very large differences in activity are observed. Homologous rat Cu-SOD is not active and indeed shows slight pro-inflammatory activity. The different SODs have different iso-electric values, different metals (Cu, Mn or Fe) at the active centre, different molecular weights and different circulation lifetimes. Biological activity is a function of amino acid sequence rather than of such secondary parameters.

Animals↗
PubMed1986

Anti-inflammatory activity of superoxide dismutases: inhibition of adriamycin induced edema in rats.

Various superoxide dismutases from different sources, containing Cu, Mn or Fe at the active centre, have been examined with respect to anti-inflammatory activity in a model using adriamycin-induced edema in rats. Very large differences in efficiency are observed, the most active being E. coli Mn-SOD and bovine Cu-SOD. The Fe-SOD from E. coli is active whereas P. leiognathi Fe-SOD is not. Human Mn-SOD shows no significant activity and homologous rat Cu-SOD is totally inactive. Yeast Cu-SOD shows pro-inflammatory properties. Anti-inflammatory activity is not a function of molecular weight or circulation life-time.

Animals↗
PubMed1986

Anti-inflammatory activity of superoxide dismutases: studies on adjuvant induced polyarthritis in rats.

The anti-arthritic activities of various superoxide dismutases and of liposomal bovine Cu-SOD have been compared in the adjuvant induced Lewis Inbred Rat model. Various approaches, including plethysmometric measurements, red cell sedimentation rates, while cell counts, levels of IgA and IgG immunoglobulins and scoring by visual, radiographic and scintigraphic techniques all concord in a demonstration of different activities for different SODs. The most efficient are liposomal bovine Cu-SOD and E. coli Mn-SOD, a moderate activity being shown by free bovine Cu-SOD. Poor or zero results are obtained with human Mn-SOD, human Cu-SOD or the homologous rat Cu-SOD.

Animals↗
PubMed1986

Anti-inflammatory activity of superoxide dismutases: comparison of enzymes from different sources in different models in rats: mechanism of action.

Comparison of the anti-inflammatory properties of superoxide dismutases from different sources using different models (carrageenan and adriamycin induced inflammation, adjuvant-induced arthritis) in rats shows a very wide range of activity from extremely good to zero. Neither circulating life time nor intracellular penetration are of importance. The mechanism of biological activity of the SODs is discussed in detail, and binding to an interphase situation on the outer cell surface is postulated. As a consequence of these various considerations it is predicted that clinical application of human Cu-SOD in humans may well be much less spectacular than is commonly assumed, and indeed may be somewhat disappointing.

Animals↗