SEARCH · Search PubMed

Results for “LIPOIC ACID”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources

PubMed1993

Electron transfer from triplet thymine and thymidine to lipoic acid.

Electron transfer from the triplet excited state of thymine or thymidine to the disulphide compound lipoic acid (RSSR) was studied using KrF laser flash photolysis (248 nm, 20 ns). The electron transfer reaction rate constants, measured at 310 nm, were determined to be 1.3 x 10(10) M-1 s-1 and 6.9 x 10(9) M-1 s-1 for thymine and thymidine respectively. The transient absorbance at 400 nm in the presence of the quencher is attributed to the anion radical of lipoic acid.

Electron Transport↗

PubMed1977

[S35 lipoic acid distribution and its effect on pyruvate dehydrogenase activity in rats with Walker carcinoma].

S35-lipoic acid injected intraperitoneally in rats with Walker carcinosarcoma in a dose of 250 mg/Kg is accumulated in their organs and tissues to much higher concentrations compared with normal animals during all terms of the observation (15 min, 1 hour, 24 hours). Differences were especially great after 24 hours. Pyruvate dehydrogenase activity in tumor rats organs was considerably reduced when calculated per 1 Kg of tissue, but it is practically unchanged when calculated per 1 mg of protein, which amount in 1 g of tissue in them is distinctly lower than in normal animals. Single injections of lipoic acid in tumor-bearing rats do restore the enzyme activity to normal (in 1 hour), while repeated ones (10 days)--prolong animals lifeterms by 25%.

Animals↗

PubMed1995

Absorption of [7,8-14C]rac-a-lipoic acid from in situ ligated segments of the gastrointestinal tract of the rat.

rac-a-Lipoic acid (CAS 62-46-4, thioctic acid) is used in human therapy besides the parenteral route also orally in gastric juice soluble galenic formulations in patients suffering from diabetic polyneuropathy which also involves the gastrointestinal tract (GI) tract in about 20% of the diabetic population. In those patients the most common manifestation of the disease due to small intestine dysfunction is diarrhoea as a consequence of which malabsorption of orally administered drugs may result. Due to the importance of the knowledge on absorption characteristics, in preclinical studies on pharmacokinetics the extent of [14C]absorption from a solution of [7,8-14C]rac-a-lipoic acid was investigated in the rat after oral administration by means of comparison of the AUCs from the [14C]plasma concentrations vs those from the intravenous route, yielding 66%. An alternative evaluation by comparison of [14C]material excreted into the urine yielded 93% [14C]absorption. Despite this high and nearly complete absorption, due to the gastroenteral disturbances mentioned above, the question was investigated if the absorption is restricted to only a small area of the GI tract or is extended over a wider area. The latter is expected to make the absorption less sensitive against variations caused by gastrointestinal disturbances due to longer residence times in the GI tract. In order to approach most closely the physiological situation--as compared with different in vitro incubation techniques using isolated GI tract sacs--the in situ technique on 5 ligated areas of the GI tract of the aneasthetized rat (stomach, duodenum, jejunum, ileum, and colon with caecum) was established.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed2002

Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity.

Mercury exposure is the second-most common cause of toxic metal poisoning. Public health concern over mercury exposure, due to contamination of fish with methylmercury and the elemental mercury content of dental amalgams, has long been a topic of political and medical debate. Although the toxicology of mercury is complex, there is evidence for antioxidant protection in the prevention of neurological and renal damage caused by mercury toxicity. Alpha-lipoic acid, a coenzyme of pyruvate and alpha-ketoglutarate dehydrogenase, has been used in Germany as an antioxidant and approved treatment for diabetic polyneuropathy for 40 years. Research has attempted to identify the role of antioxidants, glutathione and alpha-lipoic acid specifically, in both mitigation of heavy metal toxicity and direct chelation of heavy metals. This review of the literature will assess the role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity.

Animals↗

PubMed1991

[Effects of lipoic acid on reperfusion induced arrhythmias and myocardiac action potential alterations induced by free radical generating system].

By means of Langendorff method the isolated rat heart was perfused with Krebs Henseleit solution. Following ligation of the left descending coronary artery for 10 min the heart was reperfused for 3 min. The incidence of ventricular fibrillation in the reperfusion period was 100%, and the normal sinus rhythm time was shortened to 29 s within 3 min of reperfusion. Administration of lipoic acid (6.8 X 10(-6)-1.7 X 10(-4) mol/L) to the perfusate significantly reduced the incidence of ventricular fibrillation to 33-50% and prolonged the normal sinus rhythm time to 97-107 s. APA, RP, and Vmax recorded from the guinea pig papillary muscle were depressed due to the deleterious effect of xanthine oxidase and hypoxanthine free radical generating system. Under the treatment of lipoic acid (3.5 X 10(-5) mol/L), the depression of APA, RP, and Vmax were significantly relieved. This confirms that lipoic acid treatment, owing to its free radical scavenger effect, is able to protect myocardium from free radical induced electrophysiological abnormalities, and consequently decrease the incidence of malignant arrhythmias.

Action Potentials↗

PubMed1994

Naturally occurring antibodies reacting with lipoic acid: screening method, characterization and biochemical interest.

The development of a covalent enzyme-linked immunoassay (CELIA) using lipoic acid covalently bound to modified polystyrene microplates has permitted the detection, in the sera of normal BALB/c mice, of natural antibodies reacting with lipoic acid (LA). Hybridomas producing monoclonal anti-LA antibodies were obtained from splenocytes of non-immune BALB/c mice. Two of them, of IgM isotype, recognized LA but failed to react with dihydrolipoic acid (DHLA, the reduced form of LA), suggesting that the integrity of the dithiolane ring was of importance for antibody recognition. They did not give positive reactions with other disulfide linked biological molecules such as oxidized glutathione or cystine. Anti-LA antibodies, coated on polystyrene microplates, were used for the detection of free LA in a competitive assay based on peroxidase-LA conjugate.

Animals↗

PubMed1994

Identification of the dihydrolipoamide acetyltransferase subunit of the human pyruvate dehydrogenase complex as an autoantigen in halothane hepatitis. Molecular mimicry of trifluoroacetyl-lysine by lipoic acid.

Trifluoroacetylated (CF3CO-) proteins, elicited upon exposure of animals or humans to halothane, were recognized by anti-CF3CO antibody, monospecific for the hapten derivative N6-trifluoroacetyl-L-lysine. Anti-CF3CO antibodies cross-reacted with the dihydrolipoamide acetyltransferase (E2 subunit) of pyruvate dehydrogenase, indicating that epitopes on the E2 subunit of pyruvate dehydrogenase molecularly mimic those on CF3CO-proteins. Lipoic acid, the prosthetic group of the E2 subunit of pyruvate dehydrogenase was essential in this process, in that only the lipoylated form of the recombinantly expressed inner lipoyl domain of the human E2 subunit of pyruvate dehydrogenase, but not the unlipolyated form, was recognized by anti-CF3CO antibody. Furthermore, based on a high degree of structural relatedness, both CF3CO-Lys and (6RS)-lipoic acid, as well as the lipoylated peptide ETDK(lipoyl)ATIG specifically inhibited the recognition by anti-CF3CO antibody of the E2 subunit of pyruvate dehydrogenase, of trifluoroacetylated rabbit serum albumin and of human liver CF3CO-proteins. In sera of patients with halothane hepatitis, autoantibodies with properties identical to those of anti-CF3CO antibody were identified which could not discriminate between CF3CO-proteins and the E2 subunit of pyruvate dehydrogenase. These data suggest that the E2 subunit pyruvate of dehydrogenase is an autoantigen in halothane hepatitis and that molecular mimicry of CF3CO-proteins by the E2 subunit of pyruvate dehydrogenase is due to the similar structures of CF3CO-Lys and lipoic acid.

Acetyltransferases↗

PubMed1990

Subcellular localisation of dihydrolipoamide dehydrogenase and detection of lipoic acid in bloodstream forms of Trypanosoma brucei.

In the long-slender bloodstream form of Trypanosoma brucei, the enzyme dihydrolipoamide dehydrogenase exists in the absence of the 2-oxo-acid dehydrogenase complexes of which it is normally a component, and appears to be associated with the plasma membrane of the organism [Danson, M. J., Conroy, K., McQuattie, A. & Stevenson, K. J. (1987) Biochem. J. 243, 661-665]. In the present paper, a complete subcellular fractionation of T. brucei has been carried out and, by comparison with marker enzymes, it is confirmed that the dihydrolipoamide dehydrogenase is indeed associated with the plasma membrane. In addition, we now provide evidence that the distribution of the enzyme is over the whole surface of the membrane, including the flagellar pocket region, and that the enzyme is not found in any other cellular fraction. A study of the latency of the enzyme suggests that it is located on the cytoplasmic surface of the plasma membrane. The discovery of the presumed substrate of dihydrolipoamide dehydrogenase, lipoic acid, is reported for T. brucei. Using a biological assay involving a strain of Escherichia coli that requires lipoic acid for growth, we have found that acid-hydrolysed extracts of T. brucei contain 1.7 (+/- 0.2) ng of the cofactor/mg protein. The chemical nature of the lipoic acid was confirmed by gas chromatography/mass spectrometry.

Animals↗

PubMed1998

Effects of alpha-lipoic acid on neurovascular function in diabetic rats: interaction with essential fatty acids.

Elevated oxidative stress and impaired n-6 essential fatty acid metabolism contribute to defective nerve conduction velocity (NCV) and perfusion in diabetic rats, which may be corrected by free radical scavenger and gamma-linolenic acid (GLA) treatments. Alpha-lipoic acid (LPA) has antioxidant actions and both LPA racemate (racLPA) and GLA treatments produced benefits in clinical neuropathy trials. The aims were to study LPA action on neurovascular function in diabetic rats and to investigate potential interactions for co-treatment with GLA and other essential fatty acids. After 6 weeks of diabetes, 2 weeks of racLPA treatment corrected 20% sciatic motor and 14% saphenous sensory NCV deficits. The ED50 for motor NCV restoration was approximately 38 mg kg(-1) day(-1). racLPA also corrected a 49% diabetic deficit in sciatic endoneurial blood flow. R and S-LPA enantiomers were equipotent in correcting NCV and blood flow deficits. Treatment of diabetic rats with low doses (20 mg kg(-1) day(-1)) of racLPA and GLA, while having modest effects on their own, showed evidence of marked synergistic action in joint treatment, completely correcting motor NCV and blood flow deficits. This was also noted for the novel compound, SOC0150, which contains equimolar proportions of LPA and GLA (ED50 9.3 mg kg(-1) day(-1), containing 3.5 mg LPA). NCV effects also showed marked synergism when racLPA:GLA ratios were varied over a 1:3-3:1 range. In contrast, a compound containing LPA and the n-3 component, docosahexaenoic acid, showed similar activity to LPA alone. Thus, LPA-GLA interactions yield drug combinations and compounds with an order of magnitude increase in efficacy against experimental diabetic neuropathy and are worthy of consideration for clinical trials.

Animals↗

PubMed2000

Scavengers for peroxynitrite: inhibition of tyrosine nitration and oxidation with tryptamine derivatives, alpha-lipoic acid and synthetic compounds.

The inhibitory effects of various endogenous and synthetic compounds on the nitration and oxidation of L-tyrosine by peroxynitrite were examined. Nitrating and oxidizing activities were monitored by the formation of 3-nitrotyrosine and dityrosine with a HPLC-UV-fluorescence detector system, respectively. Glutathione, serotonin and synthetic sulfur- and selenium-containing compounds inhibited both the nitration and oxidation reaction of L-tyrosine effectively. However, 5-methoxytryptamine, melatonin and alpha-lipoic acid only inhibited the nitration reaction, and enhanced the formation of an oxidation product. This is important evidence that there are different intermediates in the nitrating and oxidizing reactions of L-tyrosine by peroxynitrite. It was suggested that 5-methoxytryptamine, melatonin and alpha-lipoic acid reacted only with the nitrating intermediate of peroxynitrite and inhibited nitration of L-tyrosine. Actually, the DNA strand breakage, which is believed to be a typical reaction of hydroxyl radical-like species, caused by peroxynitrite was not effectively inhibited by 5-methoxytryptamine. 5-Methoxytryptamine, melatonin and alpha-lipoic acid were viewed as useful reagents for investigating the mechanisms of damage by peroxynitrite in vitro.

Antioxidants↗

PubMed2004

L-carnitine and DL-alpha-lipoic acid reverse the age-related deficit in glutathione redox state in skeletal muscle and heart tissues.

In the present study, the glutathione redox system was evaluated as a function of age in rat heart and muscle. A decline in reduced glutathione (GSH) levels is associated with aging and many age-related diseases. The objective of this study was to determine whether L-carnitine and DL-alpha-lipoic acid could compensate for GSH depletion in protection against oxidative insults. In this study we determined reduced glutathione, oxidized glutathione (GSSG), glutathione peroxidase (GPx), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PDH) in skeletal muscle and heart of young and aged rats. We also calculated GSH/GSSG molar ratio and glutathione redox system. GSH levels were significantly lowered in aged rats than young rats. Conversely, GSSG levels were significantly high in aged rats. GSH/GSSG molar ratio and redox index were found to decreased in aged rats. The activities of GPx, GR, and G6PDH were found to be decreased in aged rats when compared with young rats. Supplementation of carnitine and lipoic acid to aged rats significantly increased the GSH levels thereby increasing the activity of GPx, GR, and G6PDH in skeletal muscle and heart of aged rats. In conclusion, our study suggests that supplementation of carnitine and lipoic acid to aged rats improves the glutathione redox system.

Aging↗

PubMed2004

The effects of the antioxidant lipoic acid on beef longissimus bloom time.

The objective of this study was to evaluate the influence of lipoic acid (LA) on beef LM steak bloom time, as well-as to characterize bloom time in the CIE L*, a*, and b* color space over a 93-min period. Thirty-two Simmental steers were supplemented with LA for 21 d immediately before slaughter at levels of 0, 8, 16, or 24 mg of LA/kg BW (eight steers per treatment). Lipoic acid was mixed with liquid paraffin, allowed to solidify, prilled, and top-dressed over a standard finishing diet. Steers were slaughtered at the University of Missouri abattoir in four groups of eight (two steers per treatment) over a 2-wk period. After a 24-h chill at 4 degrees C, the right LM was removed from each carcass. One 2.54cm steak was removed from the anterior portion of the LM, and its color characteristics (CIE L*, a*, and b*) were measured immediately with a standardized spectrocolorimeter. Color measurements were taken every 3 min thereafter for a total of 93-min. Hue angle (true red) and chroma (color saturation) were calculated from the color measurements. Addition of LA to the diet had no effect on bloom time (P = 0.67). When treatment means were analyzed, the addition of 24 mg of LA/kg BW to the diet resulted in higher (lighter) L* values (P < 0.05) compared with other treatments, whereas the addition of 16 mg of LA/kg BW to the diet caused lower hue angles (more true red; P < 0.05) when compared with other treatments. Addition of LA to the diet did not affect a* (P = 0.13) and b* (P = 0.18) values or chroma (P = 0.62). In the absence of treatment effects, bloom times for all treatments were pooled, and L* values did not change (P > 0.05) during the 93-min bloom time; however, a* and chroma values increased for 9 min and plateaued after 12 min (P < 0.01). Similarly, b* values increased (P < 0.01) for the first 6 min, and after 9 min, no further increase in yellowness was detected. Bloom time had little effect on hue angle, which stabilized after 3 min. Supplementing steers with the antioxidant LA for 21 d had no effect on the bloom time of beef LM; however, higher levels of supplemental LA affected L* values and hue angles of beef.

Animal Husbandry↗

PubMed2006

Carnitine and lipoic acid alleviates protein oxidation in heart mitochondria during aging process.

Oxidative modification alters the function of proteins and is thought to play an important role in the decline of cellular function during aging process. In the present study, we have evaluated the levels of oxidant production, protein oxidation, reduced and oxidized glutathione in young, middle aged and aged rats. The animals were divided into six groups, each group consisting of six animals each. Groups I and II were young rats, Groups III and IV were middle-aged rats and Groups V and VI were aged rats. Groups II, IV and VI were treated with carnitine (300 mg/kg bw) and Dl-alpha-Lipoic acid (100 mg/kg bw) for 28 days. Statistical significance was carried out using ANOVA. There was a significant reduction in the levels of reduced glutathione and Redox ratio (P<0.05) in aged rats whereas elevation in the levels of oxidant production, protein carbonyls, advanced oxidation protein products and oxidized glutathione were observed. Co-supplementation of carnitine and lipoic acid improved these levels to near normalcy. Thus we conclude that the utilization of carnitine and lipoic acid will lead to an improvement in the quality of living during the later stages of life by preventing free radical induced damage to the proteins.

Aging↗

PubMed2005

Treatment for diabetic mononeuropathy with alpha-lipoic acid.

Twenty-three diabetic patients -- 16 men and seven women (mean age: 50.7 +/- 17.4 years; mean duration of diabetes: 13.6 +/- 6.9 years) -- with diabetic mononeuropathy of the cranial nerves participated in the study. Four of them were with mononeuropathia multiplex and total ophthalmoplegia, affecting the oculomotor, trochlear and abducent nerves; 12 with paresis of the oculomotor nerve, one -- of the trochlear nerve and six -- of the abducent nerve. They were treated with alpha-lipoic acid (600 mg) for 10 days daily intravenously, thereafter one film tablet of 600 mg daily for 60 days. On the 10th day, we found significant improvement in the clinical signs of diabetic mononeuropathy - double vision, motility and position of the eyeball, ptosis of the upper eyelid and mydriasis. The mean period of oral treatment was 69.1 +/- 23.8 days, following the 10-day intravenous application of alpha-lipoic acid, and full recovery of the diabetic mononeuropathy was achieved with this therapeutic approach. Peripheral neuropathy was present in 17 patients (74%). On the 10th day, we established a decrease in total symptom score by an average of 2.7 +/- 1.4 points and by the end of the treatment period it was improved by 5.9 +/- 1.9 points (p = 0.04). On the 10th day, we found a decrease of 33% in foot pain and by the end of the second month, it fell by 65.5% (p < 0.0001). Vibration perception threshold was reduced in these patients at entry -- mean: 2.42 +/- 1.8 at the great toe, 2.89 +/- 1.8 at the first metatarsal and 3.65 +/- 1.7 at the medial malleolus. By the end of the second month, it reached mean 4.7 +/- 1.8 (p < 0.002) at the great toe, 4.92 +/- 2.1 (p = 0.004) at the first metatarsal and 5.3 +/- 1.4 (p < 0.01) at the medial malleolus. Cardiovascular autonomic neuropathy was present in two of the patients and there was improvement after treatment in the Ewing's tests -- Valsalva manoeuvre, deep-breathing test and lying-to-standing test. The results of our study demonstrate that alpha-lipoic acid appears to be an effective drug in the treatment for not only peripheral and autonomic diabetic neuropathy, but also diabetic mononeuropathy of the cranial nerves leading to full recovery of the patients.

Administration, Oral↗

PubMed1992

HPLC-methods for determination of lipoic acid and its reduced form in human plasma.

A method has been developed for the HPLC analysis of lipoic acid and its reduced form (dihydrolipoic acid) in biological samples. Both substances are released from the samples by enzymatic hydrolysis and extracted by solid phase column. The extracts, after evaporation, were chromatographed and quantified by electrochemical detection. The basic level was in the range 1-25 ng/ml for lipoic acid and 33-145 ng/ml for dihydrolipoic acid (6 healthy volunteers).

Chromatography, High Pressure Liquid↗

PubMed2005

Protein oxidative damage in arsenic induced rat brain: influence of DL-alpha-lipoic acid.

A body of evidence has accumulated implicating free radical generation and reaction of arsenic with protein thiols in the biochemical and molecular mechanisms of arsenic toxicity. Brain readily undergoes oxidative damage, so it is important to determine whether arsenic-induced changes in rat brain may be associated with oxidative events. An increase in oxidative stress may contribute to the development of protein damage in rat brain. Present experiments were performed to study the effect of arsenic (sodium arsenite, 100 ppm mixed in drinking water) on protein oxidation and further to demonstrate the potential of dl-alpha-lipoic acid (70 mg/kg body weight) against arsenic-induced changes in different anatomic regions (cortex, striatum, cerebellum, hypothalamus and hippocampus) of the brain of male Wistar rats. We report here that arsenic treated rats had a significantly higher level of oxidised protein as assessed by increased carbonyl residues and decreased protein thiols (protein sulfhydryls) as compared to control rats in all five regions studied, with the most notable changes occurring in the cortex, striatum and hippocampus. Coadministration of lipoic acid along with arsenic resulted in reversal of the arsenic induced trends in carbonyl and sulfhydryl concentrations. The results of the study showed, lipoic acid treatment reduces oxidative protein damage in arsenic intoxicated rat brain regions, which is associated with its antioxidant activity that combines free radical scavenging and metal chelating properties.

Animals↗

PubMed1996

alpha-Lipoic acid protects against reperfusion injury following cerebral ischemia in rats.

Ischemic-reperfusion injury in humans occurs in conditions such as stroke, cardiac arrest, subarachnoid hemorrhage or head trauma. Maximal tissue damage is observed during reperfusion, which is primarily attributed to oxidative injury resulting from production of oxygen free radicals. One of the major consequences of such damage is the depletion of the cellular antioxidant, glutathione (GSH) leading to oxidation of protein thiols to disulfides and the loss of activity of critical enzymes having active thiol group(s). Thus, the maintenance of thiol homeostasis is an important factor in cell survival. The effect of thiol antioxidants like alpha-lipoic acid and the isopropyl ester of GSH was examined on the morbidity and mortality of rats subjected to reperfusion following cerebral ischemia induced by bilateral carotid artery occlusion and hypotension. While the GSH isopropyl ester had no significant protective effect; after pretreatment of rats, alpha-lipoic acid was detected in the rat brain and it dramatically reduced the mortality rate from 78% to 26% during 24 h of reperfusion. The natural thiol antioxidant, alpha-lipoic acid is effective in improving survival and protecting the rat brain against reperfusion injury following cerebral ischemia.

Animals↗

PubMed2002

Mitochondrial decay in the aging rat heart: evidence for improvement by dietary supplementation with acetyl-L-carnitine and/or lipoic acid.

Mitochondrial decay has been postulated to be a significant underlying part of the aging process. Decline in mitochondrial function may lead to cellular energy deficits, especially in times of greater energy demand, and compromise vital ATP-dependent cellular operations, including detoxification, repair systems, DNA replication, and osmotic balance. Mitochondrial decay may also lead to enhanced oxidant production and thus render the cell more prone to oxidative insult. In particular, the heart may be especially susceptible to mitochondrial dysfunction due to myocardial dependency on beta-oxidation of fatty acids for energy and the postmitotic nature of cardiac myocytes, which would allow for greater accumulation of mitochondrial mutations and deletions. Thus, maintenance of mitochondrial function may be important to maintain overall myocardial function. Herein, we review the major age-related changes that occur to mitochondria in the aging heart and the evidence that two such supplements, acetyl-l-carnitine (ALCAR) and (R)-alpha-lipoic acid, may improve myocardial bioenergetics and lower the increased oxidative stress associated with aging. We and others have shown that feeding old rats ALCAR reverses the age-related decline in carnitine levels and improves mitochondrial beta-oxidation in a number of tissues studied. However, ALCAR supplementation does not appear to reverse the age-related decline in cardiac antioxidant status and thus may not substantially alter indices of oxidative stress. Lipoic acid, a potent thiol antioxidant and mitochondrial metabolite, appears to increase low molecular weight antioxidant status and thereby decreases age-associated oxidative insult. Thus, ALCAR along with lipoic acid may be effective supplemental regimens to maintain myocardial function.

Acetylcarnitine↗