The Experts below are selected from a list of 55573233 Experts worldwide ranked by ideXlab platform
Olof Breuer - One of the best experts on this subject based on the ideXlab platform.
-
the oxysterols cholest 5 ene 3β 4α diol cholest 5 ene 3β 4β diol and cholestane 3β 5α 6α triol are formed during in vitro oxidation of low density lipoprotein and are present in human atherosclerotic plaques
Biochimica et Biophysica Acta, 1996Co-Authors: Olof Breuer, Erik G. Lund, Susanna Dzeletovic, Ulf DiczfalusyAbstract:Isolated human low density lipoprotein (LDL) was oxidized with either cupric ions or soybean lipoxygenase and linoleic acid. Cholesterol oxidation products (oxysterols) were determined by isotope dilution gas chromatography-mass spectrometry. A new cholestane-3,5,6-triol isomer, cholestane-3β,5α,6α-triol, which has not previously been recognized as a cholesterol autoxidation product, was found at similar concentrations as the well-known cytotoxic cholestane-3β,5α,6β-triol during both copper- and lipoxygenase-mediated LDL oxidation. Furthermore, two epimeric cholest-5-ene-3β,4-diols. were identified in the oxidized LDL at similar concentrations. These two isomers were also identified in human atherosclerotic tissue in a ratio of 1:1 at a concentration more than 10-times higher than in non-atherosclerotic vessels. In vitro oxidation of LDL under an 1802 atmosphere revealed that molecular oxygen was the only source of the oxygen functions at C-4 in the cholest-5-ene-3β,4-diols. Taken together, these findings suggest that the cholest-5-ene-3β,4-diols in atherosclerotic plaques are formed by autoxidation.
-
use of an 18o2 inhalation technique and mass isotopomer distribution analysis to study oxygenation of cholesterol in rat evidence for in vivo formation of 7 oxo 7β hydroxy 24 hydroxy and 25 hydroxycholesterol
Journal of Biological Chemistry, 1995Co-Authors: Olof BreuerAbstract:Abstract Cholesterol oxidation products (oxysterols) have been detected in many different tissues, often at concentrations 103 to 104 times lower than cholesterol. This constitutes a considerable risk of quantitation errors, since even a minor oxidation of cholesterol during sample processing would yield a substantial increase of oxysterol levels. It has therefore been suggested that some of the oxysterols do not occur in vivo and their detection in tissues merely are artifacts produced in vitro. In the present work, an 18O2 inhalation technique was developed in order to clarify which oxysterols are produced in vivo. Rats were exposed for 3 h to an atmosphere with a composition similar to normal air, except that it contained 18O2 instead of 16O2. Control rats were kept in 16O2-containing atmosphere throughout the experiment. The 18O enrichment of oxysterols in plasma and liver was determined by gas/liquid chromatography-mass spectrometry and mass isotopomer distribution analysis. In vivo formation of oxysterols, indicated by enrichment in 18O, was established for cholest-5-ene-3β,7α-diol, cholest-5-ene-3β,7β-diol, 7-oxocholesterol, cholest-5-ene-3β,24-diol, cholest-5-ene-3β,25-diol, and cholest-5-ene-3β,27-diol. Additionally, it seems likely that cholest-5-ene-3β,4β-diol is formed in vivo. The 18O labeling pattern suggests that there is incomplete equilibration between the liver and plasma pools of cholest-5-ene-3β,27-diol. No evidence for the in vivo formation of 5,6-oxygenated oxysterols was obtained.
-
determination of cholesterol oxidation products in human plasma by isotope dilution mass spectrometry
Analytical Biochemistry, 1995Co-Authors: Susanna Dzeletovic, Erik G. Lund, Olof Breuer, Ulf DiczfalusyAbstract:Abstract A method based on isotope dilution-mass spectrometry was developed for the determination of nine cholesterol oxidation products in human plasma. The cholesterol oxidation products determined were cholest-5-ene-3 β,7 α-diol, cholest-5-ene-3 β,7β-diol (7α- and 7β-hydroxycholesterol, respectively), 3β-hydroxycholest-5-en-7-one (7-oxocholesterol), 5,6α-epoxy-5α-cholestan-3β-ol (cholesterol-5α,6α-epoxide), 5,6β-epoxy- 5β-cholestan-3β-ol (cholesterol-5β,6β-epoxide), cholestane-3β,5α,6β-triol, cholest-5-ene-3β,24-diol (24-hydroxycholesterol), cholest-5-ene-3β,25-diol (25-hydroxycholesterol), and cholest-5-ene-3β,27-diol (27-hydroxycholesterol). A corresponding deuterium-labeled internal standard, containing 3 to 6 deuterium atoms, was synthesized for each cholesterol oxidation product except 5β,6β-epoxycholesterol which was determined using the internal standard for 5α,6α-epoxycholesterol. Plasma from 31 healthy volunteers was analyzed by the new method and 27-, 24-, and 7α-hydroxycholesterol were the most abundant cholesterol oxidation products (mean values 154, 64, and 43 ng/ml, respectively). The other oxysterols determined were present in concentrations lower than 30 ng/ml. Males had higher 27-hydroxycholesterol concentrations in plasma than females. The 5,6-oxygenated products were present mainly unesterified while the other oxidation products were mostly in esterified form.
Ulf Diczfalusy - One of the best experts on this subject based on the ideXlab platform.
-
the oxysterols cholest 5 ene 3β 4α diol cholest 5 ene 3β 4β diol and cholestane 3β 5α 6α triol are formed during in vitro oxidation of low density lipoprotein and are present in human atherosclerotic plaques
Biochimica et Biophysica Acta, 1996Co-Authors: Olof Breuer, Erik G. Lund, Susanna Dzeletovic, Ulf DiczfalusyAbstract:Isolated human low density lipoprotein (LDL) was oxidized with either cupric ions or soybean lipoxygenase and linoleic acid. Cholesterol oxidation products (oxysterols) were determined by isotope dilution gas chromatography-mass spectrometry. A new cholestane-3,5,6-triol isomer, cholestane-3β,5α,6α-triol, which has not previously been recognized as a cholesterol autoxidation product, was found at similar concentrations as the well-known cytotoxic cholestane-3β,5α,6β-triol during both copper- and lipoxygenase-mediated LDL oxidation. Furthermore, two epimeric cholest-5-ene-3β,4-diols. were identified in the oxidized LDL at similar concentrations. These two isomers were also identified in human atherosclerotic tissue in a ratio of 1:1 at a concentration more than 10-times higher than in non-atherosclerotic vessels. In vitro oxidation of LDL under an 1802 atmosphere revealed that molecular oxygen was the only source of the oxygen functions at C-4 in the cholest-5-ene-3β,4-diols. Taken together, these findings suggest that the cholest-5-ene-3β,4-diols in atherosclerotic plaques are formed by autoxidation.
-
determination of cholesterol oxidation products in human plasma by isotope dilution mass spectrometry
Analytical Biochemistry, 1995Co-Authors: Susanna Dzeletovic, Erik G. Lund, Olof Breuer, Ulf DiczfalusyAbstract:Abstract A method based on isotope dilution-mass spectrometry was developed for the determination of nine cholesterol oxidation products in human plasma. The cholesterol oxidation products determined were cholest-5-ene-3 β,7 α-diol, cholest-5-ene-3 β,7β-diol (7α- and 7β-hydroxycholesterol, respectively), 3β-hydroxycholest-5-en-7-one (7-oxocholesterol), 5,6α-epoxy-5α-cholestan-3β-ol (cholesterol-5α,6α-epoxide), 5,6β-epoxy- 5β-cholestan-3β-ol (cholesterol-5β,6β-epoxide), cholestane-3β,5α,6β-triol, cholest-5-ene-3β,24-diol (24-hydroxycholesterol), cholest-5-ene-3β,25-diol (25-hydroxycholesterol), and cholest-5-ene-3β,27-diol (27-hydroxycholesterol). A corresponding deuterium-labeled internal standard, containing 3 to 6 deuterium atoms, was synthesized for each cholesterol oxidation product except 5β,6β-epoxycholesterol which was determined using the internal standard for 5α,6α-epoxycholesterol. Plasma from 31 healthy volunteers was analyzed by the new method and 27-, 24-, and 7α-hydroxycholesterol were the most abundant cholesterol oxidation products (mean values 154, 64, and 43 ng/ml, respectively). The other oxysterols determined were present in concentrations lower than 30 ng/ml. Males had higher 27-hydroxycholesterol concentrations in plasma than females. The 5,6-oxygenated products were present mainly unesterified while the other oxidation products were mostly in esterified form.
Thierry Bordet - One of the best experts on this subject based on the ideXlab platform.
-
olesoxime cholest 4 en 3 one oxime analgesic and neuroprotective effects in a rat model of painful peripheral neuropathy produced by the chemotherapeutic agent paclitaxel
Pain, 2009Co-Authors: Wen Hua Xiao, Thierry Bordet, Felix Y Zheng, Gary J Bennett, Rebecca PrussAbstract:Olesoxime is a small cholesterol-like molecule that was discovered in a screening program aimed at finding treatment for amyotrophic lateral sclerosis and other diseases where motor neurons degenerate. In addition to its neuroprotective and pro-regenerative effects on motor neurons in vitro and in vivo, it has been shown to have analgesic effects in rat models of painful peripheral neuropathy due to vincristine and diabetes. We used a rat model of painful peripheral neuropathy produced by the chemotherapeutic agent, paclitaxel, to determine whether olesoxime could reverse established neuropathic pain. In addition, we determined whether giving olesoxime during the exposure to paclitaxel could prevent the development of the neuropathic pain syndrome and the accompanying degeneration of the terminal arbors of sensory fibers in the epidermis. Olesoxime significantly reduced established mechano-allodynia and mechano-hyperalgesia. There was no indication of tolerance to the effect during five days of dosing and the analgesia persisted for 5-10 days after the last injection. Giving olesoxime during the exposure to paclitaxel significantly and permanently reduced the severity of mechano-allodynia and mechano-hyperalgesia and significantly reduced the amount of sensory terminal arbor degeneration. Olesoxime targets mitochondrial proteins and its effects are consistent with the mitotoxicity hypothesis for paclitaxel-evoked painful peripheral neuropathy. We conclude that olesoxime may be useful clinically for both the prevention and treatment of paclitaxel-evoked painful peripheral neuropathy.
-
specific antinociceptive activity of cholest 4 en 3 one oxime tro19622 in experimental models of painful diabetic and chemotherapy induced neuropathy
Journal of Pharmacology and Experimental Therapeutics, 2008Co-Authors: Thierry Bordet, Bruno Buisson, Magali Michaud, Jeanlouis Abitbol, Fabien Marchand, John Grist, Emile Andriambeloson, Marzia Malcangio, Rebecca PrussAbstract:Diabetes and cancer chemotherapies are often associated with painful neuropathy. The mechanisms underlying neuropathic pain remain poorly understood, and the current therapies have limited efficacy and are associated with dose-limiting side effects. We recently described the pharmacological characterization of Cholest-4-en-3-One, oxime (TRO19622), a cholesterol-like compound, that significantly reduced axonal degeneration and accelerated recovery of motor nerve conduction in a model of peripheral neuropathy induced by crushing the sciatic nerve. These results triggered investigation of efficacy in other preclinical models of peripheral neuropathy. Here, we report evidence that daily oral administration of TRO19622, while similarly improving motor nerve conduction impaired in streptozotocin-induced diabetic rats, also reversed neuropathic pain behavior as early as the first administration. Further exploration of these acute antinociceptive effects demonstrated that TRO19622 was also able to reverse tactile allodynia in vincristine-treated rats, a model of chemotherapy-induced neuropathic pain. It is interesting to note that TRO19622 did not have analgesic activity in animal models of pain produced by formalin injection, noxious thermal or mechanical stimulation, or chronic constriction injury of the sciatic nerve, indicating that painful diabetic or chemotherapy-induced neuropathies share a common mechanism that is distinct from acute, inflammationdriven, or lesion-induced neuropathic pain. These results support the potential use of TRO19622 to treat painful diabetic and chemotherapy-induced neuropathies.
-
identification and characterization of cholest 4 en 3 one oxime tro19622 a novel drug candidate for amyotrophic lateral sclerosis
Journal of Pharmacology and Experimental Therapeutics, 2007Co-Authors: Thierry Bordet, Bruno Buisson, Magali Michaud, Cyrille Drouot, Pascale Galea, Pierre Delaage, Natalia P Akentieva, Alex S Evers, Douglas F Covey, Mariano A OstuniAbstract:Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive death of cortical and spinal motor neurons, for which there is no effective treatment. Using a cell-based assay for compounds capable of preventing motor neuron cell death in vitro, a collection of approximately 40,000 low-molecular-weight compounds was screened to identify potential small-molecule therapeutics. We report the identification of Cholest-4-en-3-One, oxime (TRO19622) as a potential drug candidate for the treatment of ALS. In vitro, TRO19622 promoted motor neuron survival in the absence of trophic support in a dose-dependent manner. In vivo, TRO19622 rescued motor neurons from axotomy-induced cell death in neonatal rats and promoted nerve regeneration following sciatic nerve crush in mice. In SOD1 G93A transgenic mice, a model of familial ALS, TRO19622 treatment improved motor performance, delayed the onset of the clinical disease, and extended survival. TRO19622 bound directly to two components of the mitochondrial permeability transition pore: the voltage-dependent anion channel and the translocator protein 18 kDa (or peripheral benzodiazepine receptor), suggesting a potential mechanism for its neuroprotective activity. TRO19622 may have therapeutic potential for ALS and other motor neuron and neurodegenerative diseases.
Melha Kendel - One of the best experts on this subject based on the ideXlab platform.
-
Lipid composition, fatty acids and sterols in the seaweeds ulva armoricana, and solieria chordalis from brittany (France): An analysis from nutritional, chemotaxonomic, and antiproliferative activity perspectives
Marine Drugs, 2015Co-Authors: Melha Kendel, Gaëtane Wielgosz-collin, Christos Roussakis, Samuel Bertrand, Nathalie Bourgougnon, Gilles BedouxAbstract:Lipids from the proliferative macroalgae Ulva armoricana (Chlorophyta) and Solieria chordalis (Rhodophyta) from Brittany, France, were investigated. The total content of lipids was 2.6% and 3.0% dry weight for U. armoricana and S. chordalis, respectively. The main fractions of S. chordalis were neutral lipids (37%) and glycolipids (38%), whereas U. armoricana contained mostly neutral lipids (55%). Polyunsaturated fatty acids (PUFA) represented 29% and 15% of the total lipids in U. armoricana and S. chordalis, respectively. In both studied algae, the phospholipids were composed of PUFA for 18%. In addition, PUFA were shown to represent 9% and 4.5% of glycolipids in U. armoricana and S. chordalis, respectively. The essential PUFA were 16:4n-3, 18:4n-3, 18:2n-3, 18:2n-6, and 22:6n-3 in U. armoricana, and 20:4n-6 and 20:5n-3 in S. chordalis. It is important to notice that six 2-hydroxy-, three 3-hydroxy-, and two monounsaturated hydroxy fatty acids were also identified and may provide a chemotaxonomic basis for algae. These seaweeds contained interesting compounds such as squalene, α-tocopherol, Cholest-4-en-3-One and phytosterols. The antiproliferative effect was evaluated in vitro on human non-small-cell bronchopulmonary carcinoma line (NSCLC-N6) with an IC50 of 23 μg/mL for monogalactosyldiacylglycerols isolated from S. chordalis and 24 μg/mL for digalactosyldiacylglycerols from U. armoricana. These results confirm the potentialities of valorization of these two species in the fields of health, nutrition and chemotaxonomy.
-
seasonal composition of lipids fatty acids and sterols in the edible red alga grateloupia turuturu
Journal of Applied Phycology, 2013Co-Authors: Melha Kendel, Joel Fleurence, Gilles Barnathan, Aurelie Couzinetmossion, Michele Viau, Gaetane WielgoszcollinAbstract:Composition of lipids, sterols, fatty acids (FA), and phospholipids in the edible Rhodophyta Grateloupia turuturu from Britanny, France, was investigated over four seasons in order to identify compounds with potential benefits in health and nutrition. The lipid content was found to vary from 3.3 to 4.1 % dry weight. No marked variations were observed for glycolipids accounting for 42.3–46.8 %, whereas neutral lipids and phospholipids fluctuated from 20.1 % (summer) to 41.8 % (winter), and 11.2 % (winter) to 33.4 % (summer), respectively. Polyunsaturated FA of the total lipids were found from 20.4 % (winter) to 31.1 % (summer), including 20:5 ω3 acid as the major one (up to 16.3 % in summer). Phosphatidylcholine (20.0–43.7 %) and phosphatidylserine (24.6–37.5 %) were the dominant phospholipids in all seasons. Compounds of interest were identified in minor amounts such as squalene, α-tocopherol, phytonadione (vitamin K1), cholesteryl formate, Cholest-4-en-3-One, and cholesta-4,6-dien-3-one. Cholesterol was the major sterol with a lower content in spring and summer.
Gilles Bedoux - One of the best experts on this subject based on the ideXlab platform.
-
Lipid composition, fatty acids and sterols in the seaweeds ulva armoricana, and solieria chordalis from brittany (France): An analysis from nutritional, chemotaxonomic, and antiproliferative activity perspectives
Marine Drugs, 2015Co-Authors: Melha Kendel, Gaëtane Wielgosz-collin, Christos Roussakis, Samuel Bertrand, Nathalie Bourgougnon, Gilles BedouxAbstract:Lipids from the proliferative macroalgae Ulva armoricana (Chlorophyta) and Solieria chordalis (Rhodophyta) from Brittany, France, were investigated. The total content of lipids was 2.6% and 3.0% dry weight for U. armoricana and S. chordalis, respectively. The main fractions of S. chordalis were neutral lipids (37%) and glycolipids (38%), whereas U. armoricana contained mostly neutral lipids (55%). Polyunsaturated fatty acids (PUFA) represented 29% and 15% of the total lipids in U. armoricana and S. chordalis, respectively. In both studied algae, the phospholipids were composed of PUFA for 18%. In addition, PUFA were shown to represent 9% and 4.5% of glycolipids in U. armoricana and S. chordalis, respectively. The essential PUFA were 16:4n-3, 18:4n-3, 18:2n-3, 18:2n-6, and 22:6n-3 in U. armoricana, and 20:4n-6 and 20:5n-3 in S. chordalis. It is important to notice that six 2-hydroxy-, three 3-hydroxy-, and two monounsaturated hydroxy fatty acids were also identified and may provide a chemotaxonomic basis for algae. These seaweeds contained interesting compounds such as squalene, α-tocopherol, Cholest-4-en-3-One and phytosterols. The antiproliferative effect was evaluated in vitro on human non-small-cell bronchopulmonary carcinoma line (NSCLC-N6) with an IC50 of 23 μg/mL for monogalactosyldiacylglycerols isolated from S. chordalis and 24 μg/mL for digalactosyldiacylglycerols from U. armoricana. These results confirm the potentialities of valorization of these two species in the fields of health, nutrition and chemotaxonomy.