..oltre che ottimo veicolatore glucidico ecc..
1: Drug Metab Dispos 2001 Jun;29(6):855-62 Related Articles, Books, LinkOut
New metabolic pathways of alpha-lipoic acid.
Schupke H, Hempel R, Peter G, Hermann R, Wessel K, Engel J, Kronbach T.
Department of Metabolism and Development, elbion AG, Radebeul, Germany. Hubert.Schupke@elbion.de
The excretion and biotransformation of rac-alpha-lipoic acid (LA), which is used for the symptomatic treatment of diabetic polyneuropathy, were investigated following single oral dosing of [(14)C]LA to mice (30 mg/kg), rats (30 mg/kg), dogs (10 mg/kg), and unlabeled LA to humans (600 mg).
Thats right H-U-M-A-N-S!!!!!
More than 80% of the radioactivity given was renally excreted. Metabolite profiles obtained by radiometric high-performance liquid chromatography revealed that LA was extensively metabolized irrespective of the species.
"Irrespective of the species......"
Based on a new on-line liquid chromatography/tandem mass spectroscopy assay developed for negative ions, LA and a total of 12 metabolites were identified. Mitochondrial beta-oxidation played the paramount role in the metabolism of LA.
MITOCHONDRIAL BETA-OXIDATION!!!!
Thats the energy powerhouse of the cell.....
So animal take a HIKE!!!
Simultaneously, the circulating metabolites were subjected to reduction of the 1,2-dithiolane ring and subsequent S-methylation. In addition, evidence is given for the first time that the methyl sulfides formed were partly oxidized to give sulfoxides, predominantly in dogs. The disulfoxide of 2,4-bismethylmercapto-butanoic acid, the most polar metabolite identified, was the major metabolite in dogs. Furthermore, new data are presented that suggest conjugation with glycine occurred as a separate metabolic pathway in competition with beta-oxidation, predominantly in mice.
PMID: 11353754 [PubMed - indexed for MEDLINE]
Ok that one was for animal.
And yet another........
1: Exp Clin Endocrinol Diabetes 1996;104(3):284-8 Related Articles, Books, LinkOut
Improvement of insulin-stimulated glucose-disposal in type 2 diabetes after repeated parenteral administration of thioctic acid.
Jacob S, Henriksen EJ, Tritschler HJ, Augustin HJ, Dietze GJ.
Hypertension and Diabetes Research Unit, Max Grundig Clinic, Buhl, Germany.
Insulin resistance of skeletal muscle glucose uptake is a prominent feature of Type II diabetes (NIDDM); therefore, pharmacological intervention should aim to improve insulin sensitivity. Thioctic acid (TA), a naturally occurring compound, was shown to enhance glucose utilization in various experimental models after acute and chronic administration. It also increased insulin-stimulated glucose disposal in patients with NIDDM after acute administration. This pilot study was initiated to see whether this compound also augments glucose disposal in humans after repeated treatment. Twenty patients with NIDDM received TA (500 mg/ 500 ml NaCl, 0.9%) as daily infusions over a period of ten days. A hyperinsulinaemic, isoglycaemic glucose-clamp was done on day 0 and day 11.
Hello.......
Parenteral administration of TA resulted in a significant increase of insulin-stimulated glucose-disposal by about 30% (metabolic clearance rate for glucose, 2.5 +/- 0.3 vs. 3.2 +/- 0.4 ml/kg/min and insulin-sensitivity-index: 3.5 +/- 0.5 vs. 4.7 +/- 0.4 mg/kg/microU/ml; p < 0.05, Wilcoxon-Rank-Sum-Test). There were no changes in fasting plasma levels for glucose or insulin;
IMP: NO CHANGES IN FASTING plasma levels of glucose or insulin.
this can be explained, however, by the short period of treatment and observation. This is the first clinical study to show that a ten day administration of TA is able to improve resistance of insulin-stimulated glucose disposal in NIDDM.
So, even a 10-day burst can GREATLY improve your insulogenic
control.
Experimental data suggest several mechanisms in the mode of action. As the present investigation was an uncontrolled pilot trial, the encouraging results call for controlled studies to further elucidate the clinical relevance of the findings and the mode of action of this compound.
PMID: 8817248 [PubMed - indexed for MEDLINE]
Now, this next one is in reference to the liver helper
post. Seems that there was ONE other substance
that merited mention.
1: Am J Clin Nutr 2000 Aug;72(2 Suppl):653S-69S Related Articles, Books, LinkOut
Thiol homeostasis and supplements in physical exercise.
Sen CK, Packer L.
Departments of Surgery and Molecular & Cellular Biochemistry, The Ohio State University Medical Center, Columbus, OH 43210-1252, USA. sen-1@medctr.osu.edu
Thiols are a class of organic sulfur derivatives (mercaptans) characterized by the presence of sulfhydryl residues. In biological systems, thiols have numerous functions, including a central role in coordinating the antioxidant defense network. Physical exercise may induce oxidative stress. In humans, a consistent marker of exercise-induced oxidative stress is blood glutathione oxidation. Physical training programs have specific effects on tissue glutathione metabolism that depend on the work program and the type of tissue. Experimental studies show that glutathione metabolism in several tissues sensitively responds to an exhaustive bout of exercise. Study of glutathione-deficient animals clearly indicates the central importance of having adequate tissue glutathione to protect against exercise-induced oxidative stress. Among the various thiol supplements studied, N-acetyl-L-cysteine and alpha-lipoic acid hold the most promise. These agents may have antioxidant effects at the biochemical level but are also known to influence redox-sensitive cell signaling.
Publication Types:
Review
Review, Tutorial
PMID: 10919972 [PubMed - indexed for MEDLINE]
The compound would be NAC or N-acetyl-Cysteine which
some people mentioned.
So, the list hecomes:
1. ALA
2. Tylers
3. N-A-C
4. Calcium D-Glucarate
5.(Optional: L-glutathione)
This will explain why NAC and ALA are very, very good
substances for liver protection and a whole list
of other things.
1: Curr Top Cell Regul 2000;36:151-80 Related Articles, Books, LinkOut
Thiol-based antioxidants.
Deneke SM.
Division of Pulmonary Diseases/Critical Care Medicine, University of Texas Health Science Center at San Antonio 78284, USA.
The thiol redox status of intracellular and extracellular compartments is critical in the determination of protein structure, regulation of enzyme activity, and control of transcription factor activity and binding.
Read this:
Thiol antioxidants act through a variety of mechanisms, including (1) as components of the general thiol/disulfide redox buffer, (2) as metal chelators, (3) as radical quenchers, (4) as substrates for specific redox reactions (GSH), and (5) as specific reductants of individual protein disulfate bonds (thioredoxin).
See those 5 mechanisms???
Well, MILK THISTLE DOES NOT TARGET THEM
ALL OF THEM!!!!!
So, that pretty much FLATTENS the pro-MT group.
I feel MT sinking............... as it bloody should be.
So, POINT, SET, and MATCH to Fonzy......
The composition and redox status of the available thiols in a given compartment is highly variable and must play a part in determining the metabolic activity of each compartment. It is generally beneficial to increase the availability of specific antioxidants under conditions of oxidant stress. Cells have devised a number of mechanisms to promote increased intracellular levels of thiols such as GSH and thioredoxin in response to a wide variety of stresses. Exogenous thiols have been used successfully to increase cell and tissue thiol levels in cell cultures, in animal models, and in humans. Increased levels of GSH and other thiols have been associated with increased tolerance to oxidant stresses in all of these systems and in some cases, with disease prevention or treatment in humans. A wide variety of thiol-related compounds have been used for these purposes. These include thiols such as GSH and its derivatives, cysteine and NAC, dithiols such as lipoic acid, which is reduced to the thiol form intracellularly, and "prothiol" compounds such as OTC, which are enzymatically converted to free thiols within the cell. In choosing a thiol for a specific function (e.g., protection of lung from oxidant exposure or protection of organs from ischemia reperfusion injury), the global effects must also be considered. For example, large increases in free thiols in the circulation are associated with toxic effects. These effects may be the result of thiyl radical-mediated reactions but could also be due to destabilizing effects of increases in thiol/disulfide ratios in the plasma, which normally is in a more oxidized state than intracellular compartments. Changes in the thiol redox gradient across cells could also adversely affect any transport or cell signaling processes, which are dependent on formation and rupture of disulfide linkages in membrane proteins. Therapeutic thiol administration has been shown to have great potential, and its efficacy should be increased by selecting compounds and methods of delivery that will minimize perturbations in the thiol status of regions external to the targeted areas.
Publication Types:
Review
Review, Academic
PMID: 10842751 [PubMed - indexed for MEDLINE]
A small abstract....
1: Drug Metab Dispos 2001 Jun;29(6):855-62 Related Articles, Books, LinkOut
New metabolic pathways of alpha-lipoic acid.
Schupke H, Hempel R, Peter G, Hermann R, Wessel K, Engel J, Kronbach T.
Department of Metabolism and Development, elbion AG, Radebeul, Germany. Hubert.Schupke@elbion.de
The excretion and biotransformation of rac-alpha-lipoic acid (LA), which is used for the symptomatic treatment of diabetic polyneuropathy, were investigated following single oral dosing of [(14)C]LA to mice (30 mg/kg), rats (30 mg/kg), dogs (10 mg/kg), and unlabeled LA to humans (600 mg).
Thats right H-U-M-A-N-S!!!!!
More than 80% of the radioactivity given was renally excreted. Metabolite profiles obtained by radiometric high-performance liquid chromatography revealed that LA was extensively metabolized irrespective of the species.
"Irrespective of the species......"
Based on a new on-line liquid chromatography/tandem mass spectroscopy assay developed for negative ions, LA and a total of 12 metabolites were identified. Mitochondrial beta-oxidation played the paramount role in the metabolism of LA.
MITOCHONDRIAL BETA-OXIDATION!!!!
Thats the energy powerhouse of the cell.....
So animal take a HIKE!!!
Simultaneously, the circulating metabolites were subjected to reduction of the 1,2-dithiolane ring and subsequent S-methylation. In addition, evidence is given for the first time that the methyl sulfides formed were partly oxidized to give sulfoxides, predominantly in dogs. The disulfoxide of 2,4-bismethylmercapto-butanoic acid, the most polar metabolite identified, was the major metabolite in dogs. Furthermore, new data are presented that suggest conjugation with glycine occurred as a separate metabolic pathway in competition with beta-oxidation, predominantly in mice.
PMID: 11353754 [PubMed - indexed for MEDLINE]
Ok that one was for animal.
And yet another........
1: Exp Clin Endocrinol Diabetes 1996;104(3):284-8 Related Articles, Books, LinkOut
Improvement of insulin-stimulated glucose-disposal in type 2 diabetes after repeated parenteral administration of thioctic acid.
Jacob S, Henriksen EJ, Tritschler HJ, Augustin HJ, Dietze GJ.
Hypertension and Diabetes Research Unit, Max Grundig Clinic, Buhl, Germany.
Insulin resistance of skeletal muscle glucose uptake is a prominent feature of Type II diabetes (NIDDM); therefore, pharmacological intervention should aim to improve insulin sensitivity. Thioctic acid (TA), a naturally occurring compound, was shown to enhance glucose utilization in various experimental models after acute and chronic administration. It also increased insulin-stimulated glucose disposal in patients with NIDDM after acute administration. This pilot study was initiated to see whether this compound also augments glucose disposal in humans after repeated treatment. Twenty patients with NIDDM received TA (500 mg/ 500 ml NaCl, 0.9%) as daily infusions over a period of ten days. A hyperinsulinaemic, isoglycaemic glucose-clamp was done on day 0 and day 11.
Hello.......
Parenteral administration of TA resulted in a significant increase of insulin-stimulated glucose-disposal by about 30% (metabolic clearance rate for glucose, 2.5 +/- 0.3 vs. 3.2 +/- 0.4 ml/kg/min and insulin-sensitivity-index: 3.5 +/- 0.5 vs. 4.7 +/- 0.4 mg/kg/microU/ml; p < 0.05, Wilcoxon-Rank-Sum-Test). There were no changes in fasting plasma levels for glucose or insulin;
IMP: NO CHANGES IN FASTING plasma levels of glucose or insulin.
this can be explained, however, by the short period of treatment and observation. This is the first clinical study to show that a ten day administration of TA is able to improve resistance of insulin-stimulated glucose disposal in NIDDM.
So, even a 10-day burst can GREATLY improve your insulogenic
control.
Experimental data suggest several mechanisms in the mode of action. As the present investigation was an uncontrolled pilot trial, the encouraging results call for controlled studies to further elucidate the clinical relevance of the findings and the mode of action of this compound.
PMID: 8817248 [PubMed - indexed for MEDLINE]
Now, this next one is in reference to the liver helper
post. Seems that there was ONE other substance
that merited mention.
1: Am J Clin Nutr 2000 Aug;72(2 Suppl):653S-69S Related Articles, Books, LinkOut
Thiol homeostasis and supplements in physical exercise.
Sen CK, Packer L.
Departments of Surgery and Molecular & Cellular Biochemistry, The Ohio State University Medical Center, Columbus, OH 43210-1252, USA. sen-1@medctr.osu.edu
Thiols are a class of organic sulfur derivatives (mercaptans) characterized by the presence of sulfhydryl residues. In biological systems, thiols have numerous functions, including a central role in coordinating the antioxidant defense network. Physical exercise may induce oxidative stress. In humans, a consistent marker of exercise-induced oxidative stress is blood glutathione oxidation. Physical training programs have specific effects on tissue glutathione metabolism that depend on the work program and the type of tissue. Experimental studies show that glutathione metabolism in several tissues sensitively responds to an exhaustive bout of exercise. Study of glutathione-deficient animals clearly indicates the central importance of having adequate tissue glutathione to protect against exercise-induced oxidative stress. Among the various thiol supplements studied, N-acetyl-L-cysteine and alpha-lipoic acid hold the most promise. These agents may have antioxidant effects at the biochemical level but are also known to influence redox-sensitive cell signaling.
Publication Types:
Review
Review, Tutorial
PMID: 10919972 [PubMed - indexed for MEDLINE]
The compound would be NAC or N-acetyl-Cysteine which
some people mentioned.
So, the list hecomes:
1. ALA
2. Tylers
3. N-A-C
4. Calcium D-Glucarate
5.(Optional: L-glutathione)
This will explain why NAC and ALA are very, very good
substances for liver protection and a whole list
of other things.
1: Curr Top Cell Regul 2000;36:151-80 Related Articles, Books, LinkOut
Thiol-based antioxidants.
Deneke SM.
Division of Pulmonary Diseases/Critical Care Medicine, University of Texas Health Science Center at San Antonio 78284, USA.
The thiol redox status of intracellular and extracellular compartments is critical in the determination of protein structure, regulation of enzyme activity, and control of transcription factor activity and binding.
Read this:
Thiol antioxidants act through a variety of mechanisms, including (1) as components of the general thiol/disulfide redox buffer, (2) as metal chelators, (3) as radical quenchers, (4) as substrates for specific redox reactions (GSH), and (5) as specific reductants of individual protein disulfate bonds (thioredoxin).
See those 5 mechanisms???
Well, MILK THISTLE DOES NOT TARGET THEM
ALL OF THEM!!!!!
So, that pretty much FLATTENS the pro-MT group.
I feel MT sinking............... as it bloody should be.
So, POINT, SET, and MATCH to Fonzy......
The composition and redox status of the available thiols in a given compartment is highly variable and must play a part in determining the metabolic activity of each compartment. It is generally beneficial to increase the availability of specific antioxidants under conditions of oxidant stress. Cells have devised a number of mechanisms to promote increased intracellular levels of thiols such as GSH and thioredoxin in response to a wide variety of stresses. Exogenous thiols have been used successfully to increase cell and tissue thiol levels in cell cultures, in animal models, and in humans. Increased levels of GSH and other thiols have been associated with increased tolerance to oxidant stresses in all of these systems and in some cases, with disease prevention or treatment in humans. A wide variety of thiol-related compounds have been used for these purposes. These include thiols such as GSH and its derivatives, cysteine and NAC, dithiols such as lipoic acid, which is reduced to the thiol form intracellularly, and "prothiol" compounds such as OTC, which are enzymatically converted to free thiols within the cell. In choosing a thiol for a specific function (e.g., protection of lung from oxidant exposure or protection of organs from ischemia reperfusion injury), the global effects must also be considered. For example, large increases in free thiols in the circulation are associated with toxic effects. These effects may be the result of thiyl radical-mediated reactions but could also be due to destabilizing effects of increases in thiol/disulfide ratios in the plasma, which normally is in a more oxidized state than intracellular compartments. Changes in the thiol redox gradient across cells could also adversely affect any transport or cell signaling processes, which are dependent on formation and rupture of disulfide linkages in membrane proteins. Therapeutic thiol administration has been shown to have great potential, and its efficacy should be increased by selecting compounds and methods of delivery that will minimize perturbations in the thiol status of regions external to the targeted areas.
Publication Types:
Review
Review, Academic
PMID: 10842751 [PubMed - indexed for MEDLINE]
A small abstract....
Commenta