INHIBITORY EFFECT OF THIOPENTONE ON THE PYRUVIC DEHYDROGENASE IN BRAIN: REVERSIBILITY OF ACTION BY THIAMINE PYROPHOSPHATE AND LIPOIC ACID

1962 ◽  
Vol 40 (1) ◽  
pp. 477-484
Author(s):  
A. R. Fahmy ◽  
H. H. Ibrahim ◽  
M. Talaat
Keyword(s):  
Brain Tissue ◽  
Lipoic Acid ◽  
Inhibitory Effect ◽  
Thiamine Pyrophosphate ◽  
Pyruvate Oxidation ◽  
Thiopentone Sodium

A study of the effect of Thiopentone sodium on pyruvate oxidation in brain tissue revealed that the action of this drug could be attributed primarily to an inhibition of pyruvic dehydrogenase, the enzyme which degrades pyruvate to the level of acetate. Of the four cofactors needed by the enzyme, thiamine pyrophosphate (TPP) and lipoic acid (Lp) modified the inhibition when added separately. The inhibition was completely relieved when thiamine pyrophosphate and lipoic acid were added together, suggesting that Thiopentone may be competing not with either alone but with a complex of the two such as "lipothiamide pyrophosphate". Alpha-Ketoglutaric dehydrogenase, which requires the same cofactors as pyruvic dehydrogenase, was somewhat less affected by Thiopentone sodium.

INHIBITORY EFFECT OF THIOPENTONE ON THE PYRUVIC DEHYDROGENASE IN BRAIN: REVERSIBILITY OF ACTION BY THIAMINE PYROPHOSPHATE AND LIPOIC ACID

1962 ◽  
Vol 40 (4) ◽  
pp. 477-484 ◽  
Author(s):  
A. R. Fahmy ◽  
H. H. Ibrahim ◽  
M. Talaat
Keyword(s):  
Brain Tissue ◽  
Lipoic Acid ◽  
Inhibitory Effect ◽  
Thiamine Pyrophosphate ◽  
Pyruvate Oxidation ◽  
Thiopentone Sodium

A study of the effect of Thiopentone sodium on pyruvate oxidation in brain tissue revealed that the action of this drug could be attributed primarily to an inhibition of pyruvic dehydrogenase, the enzyme which degrades pyruvate to the level of acetate. Of the four cofactors needed by the enzyme, thiamine pyrophosphate (TPP) and lipoic acid (Lp) modified the inhibition when added separately. The inhibition was completely relieved when thiamine pyrophosphate and lipoic acid were added together, suggesting that Thiopentone may be competing not with either alone but with a complex of the two such as "lipothiamide pyrophosphate". Alpha-Ketoglutaric dehydrogenase, which requires the same cofactors as pyruvic dehydrogenase, was somewhat less affected by Thiopentone sodium.

scholarly journals α-Lipoic Acid Potentiates the Anti-Inflammatory Activity of Avocado/Soybean Unsaponifiables in Chondrocyte Cultures

Cartilage ◽  
2017 ◽  
Vol 9 (3) ◽  
pp. 304-312 ◽  
Author(s):  
Carmelita G. Frondoza ◽  
Lowella V. Fortuno ◽  
Mark W. Grzanna ◽  
Stacy L. Ownby ◽  
Angela Y. Au ◽  
...  
Keyword(s):  
Lipoic Acid ◽  
Nuclear Factor Kappa B ◽  
Nuclear Translocation ◽  
Inhibitory Effect ◽  
Prostaglandin E ◽  
Nuclear Factor ◽  
Chondrocyte Cultures ◽  
Potent Inhibitory Effect ◽  
Anti Inflammatory ◽  
Pharmacologic Treatments

Objective Pro-inflammatory mediators such as prostaglandin E-2 (PGE2) play major roles in the pathogenesis of osteoarthritis (OA). Although current pharmacologic treatments reduce inflammation, their prolonged use is associated with deleterious side effects prompting the search for safer and effective alternative strategies. The present study evaluated whether chondrocyte production of PGE2 can be suppressed by the combination of avocado/soybean unsaponifiables (ASU) and α-lipoic acid (LA). Design Chondrocytes from articular cartilage of equine joints were incubated for 24 hours with: (1) control media, (2) ASU, (3) LA, or (4) ASU + LA combination. Cells were activated with lipopolysaccharide (LPS), interleukin 1β (IL-1β) or hydrogen peroxide (H2O2) for 24 hours and supernatants were immunoassayed for PGE2. Nuclear factor-kappa B (NF-κB) analyses were performed by immunocytochemistry and Western blot following 1 hour of activation with IL-1β. Results LPS, IL-1β, or H2O2 significantly increased PGE2 production. ASU or LA alone suppressed PGE2 production in LPS and IL-1β activated cells. Only LA alone at 2.5 µg/mL was inhibitory in H2O2-activated chondrocytes. ASU + LA inhibited more than either agent alone in all activated cells. ASU + LA also inhibited the IL-1β induced nuclear translocation of NF-κB. Conclusions The present study provides evidence that chondrocyte PGE2 production can be inhibited by the combination of ASU + LA more effectively than either ASU or LA alone. Inhibition of PGE2 production is associated with the suppression of NF-κB translocation. The potent inhibitory effect of ASU + LA on PGE2 production could offer a potential advantage for a combination anti-inflammatory/antioxidant approach in the management of OA.

scholarly journals Inhibition of oxidative metabolism by propionic acid and its reversal by carnitine in isolated rat hepatocytes

1986 ◽  
Vol 236 (1) ◽  
pp. 131-136 ◽  
Author(s):  
E P Brass ◽  
P V Fennessey ◽  
L V Miller
Keyword(s):  
Palmitic Acid ◽  
Propionic Acid ◽  
Oxidative Metabolism ◽  
Rat Hepatocytes ◽  
Inhibitory Effect ◽  
Acid Oxidation ◽  
Isolated Rat Hepatocytes ◽  
Pyruvate Oxidation ◽  
Metabolic Basis ◽  
Isolated Rat

The present study was designed to study the interaction of propionic acid and carnitine on oxidative metabolism by isolated rat hepatocytes. Propionic acid (10 mM) inhibited hepatocyte oxidation of [1-14C]-pyruvate (10 mM) by 60%. This inhibition was not the result of substrate competition, as butyric acid had minimal effects on pyruvate oxidation. Carnitine had a small inhibitory effect on pyruvate oxidation in the hepatocyte system (210 +/- 19 and 184 +/- 18 nmol of pyruvate/60 min per mg of protein in the absence and presence of 10 mM-carnitine respectively; means +/- S.E.M., n = 10). However, in the presence of propionic acid (10 mM), carnitine (10 mM) increased the rate of pyruvate oxidation by 19%. Under conditions where carnitine partially reversed the inhibitory effect of propionic acid on pyruvate oxidation, formation of propionylcarnitine was documented by using fast-atom-bombardment mass spectroscopy. Propionic acid also inhibited oxidation of [1-14C]palmitic acid (0.8 mM) by hepatocytes isolated from fed rats. The degree of inhibition caused by propionic acid was decreased in the presence of 10 mM-carnitine (41% inhibition in the absence of carnitine, 22% inhibition in the presence of carnitine). Propionic acid did not inhibit [1-14C]palmitic acid oxidation by hepatocytes isolated from 48 h-starved rats. These results demonstrate that propionic acid interferes with oxidative metabolism in intact hepatocytes. Carnitine partially reverses the inhibition of pyruvate and palmitic acid oxidation by propionic acid, and this reversal is associated with increased propionylcarnitine formation. The present study provides a metabolic basis for the efficacy of carnitine in patients with abnormal organic acid accumulation, and the observation that such patients appear to have increased carnitine requirements (‘carnitine insufficiency’).

Inhibitory Effect of α-Lipoic Acid on Platelet Aggregation Is Mediated by PPARs

2011 ◽  
Vol 59 (7) ◽  
pp. 3050-3059 ◽  
Author(s):  
Tz-Chong Chou ◽  
Ching-Yu Shih ◽  
Ying-Tsung Chen
Keyword(s):  
Platelet Aggregation ◽  
Lipoic Acid ◽  
Inhibitory Effect

scholarly journals In vitro Inhibitory Effects of Cyperus esculentus L. (Tiger Nut) Tubers on some Enzymes Associated with Neurodegeneration and Iron- Induced Lipid Peroxidation in Rats’ Brain Tissue Homogenate

2020 ◽  
Vol 11 (2) ◽  
pp. 81-87
Author(s):  
Ayodeji Olabiyi ◽  
Keyword(s):  
Lipid Peroxidation ◽  
Brain Tissue ◽  
Radical Scavenging ◽  
Inhibitory Effect ◽  
Tissue Homogenate ◽  
Cyperus Esculentus ◽  
Butyryl Cholinesterase ◽  
Radical Scavenging Ability ◽  
Brain Tissue Homogenate

This study investigated the inhibitory effect of Cyperus esculentus L. (raw and processed) tubers on Iron (Fe2+) induced lipid peroxidation and key enzymes linked with neurodegeneration in vitro. Ten grams of tiger nut tubers was weighed and added to 100 mL of distilled water (1:10 w/v), left for 24 h, filtered, centrifuged to obtain a clear supernatant and lyophilized. Activities of acetyl cholinesterase (AChE), butyryl cholinesterase (BChE), Fe2+-induced lipid peroxidation as well as antioxidants status as indicated by 2,2-azino-bis (3-ethylbenthiazoline-6-sulphonic acid radical scavenging ability and Fe chelation were evaluated. Raw tiger nut extracts inhibited activities of AChE and BChE in the brain tissue of rats (0 – 11.54 mg /mL) with EC50 = 3.599 mg /mL and 2.71 ± 0.01 mg /mL respectively, and increased antioxidant activity when compared with the processed tuber. Inhibition on these enzymes as well as prevention of Fe2+ induced lipid peroxidation may be the possible mechanism of action by which tiger nut prevents neurodegeneration.

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