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PubMed2000

Effect of DL-alpha-lipoic acid on neural antioxidants in aged rats.

The effect of DL-alpha-lipoic acid on lipid peroxidation and antioxidants were evaluated in various brain regions of young and aged rats. In aged rats, the levels of ascorbic acid, alpha-tocopherol and glutathione were low whereas the lipid peroxidation rate, as revealed by malonaldehyde content, was found to be high. Lipoic acid, an antioxidant, was administered intraperitoneally (100 mg/kg body weight/day) for 7 and 14 days. Lipoate-administered aged rats brought about reduction in lipid peroxidation and elevation in the levels of antioxidants. The modulatory effect of lipoate in decreasing age-associated alterations observed in our study proves its role as a potent antioxidant in the brain of aged rats.

Animals↗
PubMed2001

Alpha-lipoic acid as a new treatment option for Alzheimer [corrected] type dementia.

Oxidative stress and energy depletion are characteristic biochemical hallmarks of Alzheimer's disease (AD), thus antioxidants with positive effects on glucose metabolism such as thioctic (alpha-lipoic) acid should exert positive effects in these patients. Therefore, 600 mg alpha-lipoic acid was given daily to nine patients with AD and related dementias (receiving a standard treatment with acetylcholinesterase inhibitors) in an open study over an observation period of, on avarage, 337+/-80 days. The treatment led to a stabilization of cognitive functions in the study group, demonstrated by constant scores in two neuropsychological tests (mini-mental state examination: MMSE and AD assessment scale, cognitive subscale: ADAScog). Despite the fact that this study was small and not randomized, this is the first indication that treatment with alpha-lipoic acid might be a successful 'neuroprotective' therapy option for AD and related dementias.

Journal Article↗
PubMed2001

Lipoic acid metabolism in Arabidopsis thaliana: cloning and characterization of a cDNA encoding lipoyltransferase.

Lipoic acid is an essential coenzyme required for activity of several key enzyme complexes, such as the pyruvate dehydrogenase complex, in the central metabolism. In these complexes, lipoic acid must be covalently attached to one of the component proteins for it to have biological activity. We report the cloning and characterization of Arabidopsis thaliana LIP2 cDNA for lipoyltransferase that catalyzes the transfer of the lipoyl group from lipoyl-acyl carrier protein to lipoate-dependent enzymes. This cDNA was shown to code for lipoyltransferase by its ability to complement an Escherichia coli lipB null mutant lacking lipoyltransferase activity. The expressed enzyme in the E. coli mutant efficiently complemented the activity of pyruvate dehydrogenase complex, but less efficiently than that of 2-oxoglutarate dehydrogenase complex. Comparison of the deduced amino acid sequence of LIP2 with those of E. coli and yeast lipoyltransferases showed a marked sequence similarity and the presence of a leader sequence presumably required for import into mitochondria. Southern and northern hybridization analyses suggest that LIP2 is a single-copy gene and is expressed as an mRNA of 860 nt in leaves. Western blot analysis with an antibody against lipoyltransferase demonstrated that a 29 kDa form of lipoyltransferase is located in the mitochondrial compartment of A. thaliana.

Acyltransferases↗
PubMed2002

Lipoic acid in the treatment of smell dysfunction following viral infection of the upper respiratory tract.

OBJECTIVES/HYPOTHESIS: The study aimed to investigate the potential therapeutic effects of alpha-lipoic acid in olfactory loss following infections of the upper respiratory tract. Possible mechanisms of actions include the release of nerve growth factor and antioxidative effects, both of which may be helpful in the regeneration of olfactory receptor neurons. STUDY DESIGN: Unblinded, prospective clinical trial. METHODS: A total of 23 patients participated (13 women, 10 men; mean age 57 y, age range 22-79 y; mean duration of olfactory loss, 14 mo; range, 4 to 33 mo); 19 of them were hyposmic and 4 had functional anosmia. Alpha-lipoic acid was used orally at a dose of 600 mg/day; it was prescribed for an average period of 4.5 months. Olfactory function was assessed using olfactory tests for phenyl ethyl alcohol odor threshold, odor discrimination, and odor identification. RESULTS: Seven patients (30%) showed no change in olfactory function. Two patients (9%) exhibited a moderate decrease in olfactory function; in contrast, six patients (26%) showed moderate and eight patients (35%) remarkable increase in olfactory function. Two of the 4 patients with functional anosmia reached hyposmia; 5 of 19 hyposmic patients became normosmic. Overall, this resulted in a significant improvement in olfactory function following treatment (P =.002). At the end of treatment parosmias were less frequent (22%) than at the beginning of therapy (48%). Interestingly, recovery of olfactory function appeared to be more pronounced in younger patients than in patients above the age of 60 years (P =.018). CONCLUSIONS: The results indicate that alpha-lipoic acid may be helpful in patients with olfactory loss after upper respiratory tract infection. However, to judge the true potential of this treatment, the outcome of double-blind, placebo-controlled studies in large groups of patients must be awaited, especially when considering the relatively high rate of spontaneous recovery in olfactory loss after upper respiratory tract infection.

Adult↗
PubMed2002

Lipoic acid as an antioxidant in mature thoroughbred geldings: a preliminary study.

alpha-Lipoic acid (LA) has demonstrated antioxidant effects in humans and laboratory animals. The objective of this study was to determine whether the effects of LA are similar in horses. Five Thoroughbred geldings were supplemented with 10 mg/kg/d DL-alpha-lipoic acid in a molasses and sweet feed carrier and five received only the carrier as a placebo (CON). Blood samples were obtained at baseline (0 d), after 7 and 14 d of supplementation, and 48 h postsupplementation (16 d). Blood fractions of red and white blood cells (RBC and WBC, respectively) and plasma were analyzed for glutathione (GSH), glutathione peroxidase (GPx) and total plasma lipid hydroperoxides (LPO). An experienced veterinarian observed no adverse clinical effects. Plasma LPO baselines differed between groups (P = 0.002). When covariates were used, there was a decrease over time in the LA group (P = 0.015) and concentrations were lower in the LA group than in the CON group at 7 and 14 d (P = 0.022 and P = 0.0002, respectively). At baseline, GSH concentration was 69 +/- 7 in WBC and 115 +/- 13 mmol/mg protein in the RBC, with no differences resulting from either time or treatment. The GPx activity was 47 +/- 4 and 26 +/- 5 U/g protein at baseline WBC and RBC, respectively, with a lower concentration in the LA group's WBC at 7 (P = 0.019) and 14 d (P = 0.013). The results show that 10 mg/kg LA had no evident adverse effects, and moderately reduced the oxidative stress of horses allowed light activity. These findings encourage studying of LA in horses subjected to strenuous exercise.

Aging↗
PubMed2002

R-alpha-lipoic acid action on cell redox status, the insulin receptor, and glucose uptake in 3T3-L1 adipocytes.

The insulin signaling pathway has been reported to mediate R-alpha-lipoic acid- (R-LA-)-stimulated glucose uptake into 3T3-L1 adipocytes and L6 myotubes. We investigated the role of the thiol antioxidant dihydrolipoic acid (DHLA) and intracellular glutathione (GSH) in R-LA-stimulated glucose transport and explored the hypothesis that R-LA could increase glucose uptake into 3T3-L1 adipocytes in an oxidant-mimetic manner. R-LA pretreatment of 3T3-L1 cells stimulated glucose transport at early time points (30 min - 6 h), whereas it inhibited glucose uptake at later time points. Analysis of the oxidized and reduced content of LA in cells and medium showed that >90% of lipoic acid present was in its oxidized form. Furthermore, all oxidized forms of LA (S-, R-, and racemic LA) stimulated glucose uptake, whereas the reduced form, dihydrolipoic acid, was ineffective. Intracellular GSH levels were not changed at the early time points (before 12 h), while longer preincubation (24 - 48 h) of cells with R-LA significantly increased intracellular GSH. Pretreatment of adipocytes with R-LA increased intracellular peroxide levels at early time points (30 min - 6 h), after which it was decreased (12 - 48 h). R-LA also increased tyrosine phosphorylation of immunoprecipitated insulin receptors from 3T3-L1 adipocytes. These results indicate that (i) 3T3-L1 adipocytes have a low capacity to reduce R-LA and the oxidized form of lipoic acid is responsible for stimulating glucose uptake, (ii) R-LA modulates glucose uptake by changing the intracellular redox status, and (iii) the insulin receptor is a potential cellular target for R-LA action.

3T3 Cells↗
PubMed2006

Alpha-tocopherol and alpha-lipoic acid enhance the erythrocyte antioxidant defence in cyclosporine A-treated rats.

The aim of this study was to determine the effects of dietary antioxidant supplementation with alpha-tocopherol and alpha-lipoic acid on cyclosporine A (cyclosporine)-induced alterations to erythrocyte and plasma redox balance. Rats were randomly assigned to either control, antioxidant (alpha-tocopherol 1000 IU/kg diet and alpha-lipoic acid 1.6 g/kg diet), cyclosporine (25 mg/kg/day), or cyclosporine + antioxidant treatments. Cyclosporine was administered for 7 days after an 8 week feeding period. Plasma was analysed for alpha-tocopherol, total antioxidant capacity, malondialdehyde, and creatinine. Erythrocytes were analysed for glutathione, methaemoglobin, superoxide dismutase, catalase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, alpha-tocopherol and malondialdehye. Cyclosporine administration caused a significant decrease in superoxide dismutase activity (P<0.05 control versus cyclosporine) and this was improved by antioxidant supplementation (P<0.05 cyclosporine versus cyclosporine + antioxidant; P<0.05 control versus cyclosporine + antioxidant). Animals receiving cyclosporine and antioxidants showed significantly increased (P<0.05) catalase activity compared to both groups not receiving cyclosporine. Cyclosporine administration induced significant increases in plasma malondialdehyde and creatinine concentration (P<0.05 control versus cyclosporine). Antioxidant supplementation prevented the cyclosporine induced increase in plasma creatinine (P<0.05 cyclosporine versus cyclosporine + antioxidant; P>0.05 control versus cyclosporine + antioxidant), however, supplementation did not alter the cyclosporine induced increase in plasma malondialdehyde concentration (P>0.05 cyclosporine versus cyclosporine + antioxidant). Antioxidant supplementation resulted in significant increases (P<0.05) in plasma and erythrocyte alpha-tocopherol in both of the supplemented groups compared to non-supplemented groups. In conclusion, dietary supplementation with alpha-tocopherol and alpha-lipoic acid enhanced the erythrocyte antioxidant defence and reduced nephrotoxicity in cyclosporine treated animals.

Animals↗
PubMed2003

Antioxidant activities of novel alpha-lipoic acid derivatives: N-(6, 8-dimercaptooctanoyl)-2-aminoethanesulfonate- and N-(6, 8-dimercaptooctanoyl)-L-aspartate-zinc complex.

Two new compounds, sodium N-(6, '8-dimercaptooctanoyl)-2-amino ethanesulfonate- and sodium N-(6, 8-dimercaptooctanoyl)-L-aspartate - zinc complex were synthesized from alpha-lipoyl-2-aminoethanesulfonate and alpha-lipoyl-L- aspartate by reduction of zinc/acetic acid respectively. These alpha-lipoyl-amino acids were obtained by a coupling of alpha-lipoic acid and 2-aminoethanesulfonate or L-aspartate, using a mixed anhydride method. Scavenging activities of these derivatives against hydroxyl radicals (*OH) was demonstrated directly using electron spin resonance (ESR) spectrometry with spin trapping. Otherwise an apparent superoxide anion radical (O2*-) scavenging effect of these derivatives may be due to the inhibition of 02*- generation system, i.e., xanthine oxidase. Scavenging activities of these compounds against nitric oxide radicals (NO*), and peroxynitrite (ONOO-) were estimated by the flow injection analysis using the Griess reagent and by a fluorescence spectrometry using dihydrorhodamine 123 respectively. Meanwhile, these derivatives showed protective effects against lipid peroxidation and protein carbonyl formation. Scavenging activities against NO* and ONOO-, and inhibitory effects on protein carbonyl formation of these derivatives were much stronger than these of alpha-lipoic acid itself.

Alkanesulfonates↗
PubMedDate not supplied

Effect of DL alpha-lipoic acid in glyoxylate-induced acute lithiasis.

Glyoxylic lithiasis by acute intoxication with sodium glyoxylate, significantly raised the levels of renal tissue calcium and oxalate which has been reflected simultaneously in their urinary levels. Administration of DL alpha-lipoic acid lowered the oxalate levels in the kidney and urine. Sodium glyoxylate administration resulted in enhanced liver glycollate oxidase activity, the major enzyme in endogenous oxalate synthesis. DL alpha-lipoic acid decreased glycollate oxidase activity but did not have any effect on lactate dehydrogenase. The possibility of regulating oxalate metabolism in glyoxylic lithiasis with the use of DL alpha-lipoic acid, by way of inhibiting liver glycollate oxidase, looks attractive.

Alcohol Oxidoreductases↗
PubMed2000

Effect of DL-alpha-lipoic acid on tissue nucleic acid contents in aged rats.

We have attempted to evaluate the effect of DL-alpha-lipoic acid on nucleic acid and protein contents in young and aged rats. An age-associated decrease in the deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and protein contents were observed in aged rats. DL-alpha-lipoic acid was administered intraperitoneally (100 mg/kg body weight/day) to young and aged rats from 7 and 14 days. Lipoate administration demonstrated a substantial increase in nucleic acid and protein contents in aged rats. Hence it can be justified that lipoate is functionally efficient in helping the cell to recover from oxidative damage.

Aging↗
PubMedDate not supplied

Burning Mouth Syndrome: open trial of psychotherapy alone, medication with alpha-lipoic acid (thioctic acid), and combination therapy.

OBJECTIVE AND STUDY DESIGN: This open study of 192 otherwise healthy persons with burning mouth syndrome, examined the efficacy on control of symptoms of psychotherapy alone with two hour sessions weekly for two months; alpha lipoic acid (ALA, tioctic acid; Tiobec) 600 mg/day alone for two months; or combination therapy of psychoanalysis and 600 mg/day ALA for two months. Controls received placebo alone. RESULTS: Most benefit was obtained with combination therapy. Combination therapy of psychoanalysis and alpha lipoic acid (ALA, tioctic acid; Tiobec. 600 mg/day) for two months gave most benefit and significantly more than psychoanalysis alone for two 1 hour sessions weekly for two months (p<0.0005), or ALA 600 mg/day alone for two months (p<0.0005). CONCLUSION: The present results suggest that alpha lipoic acid may complement psychotherapy and can be an acceptable alternative to psychoactive agents, but trials to compare the two approaches are now warranted.

Adult↗
PubMedDate not supplied

Protective activity of hesperidin and lipoic acid against sodium arsenite acute toxicity in mice.

The objective of the present work was to evaluate the toxic effects of sodium arsenite, As(III), in mice and the protective effect of 2 antioxidants, hesperidin and lipoic acid, against the observed As(III)-induced toxicity. In each study, mice were assigned to 1 of 4 groups: control, antioxidant, antioxidant + arsenite, and arsenite. Animals were first injected with the vehicle or 25 mg antioxidant/kg BW. After 30 minutes they received an injection of 10 mg arsenite/kg BW or 0.9% NaCl. Two hours after the first injection, the liver, kidney, and testis were collected for histological evaluation. Liver samples were also taken for quantification of arsenic. In mice exposed only to As(III), various histopathological effects were observed in the liver, kidneys, and testes. In mice pretreated with either hesperidin or lipoic acid, a reduction of histopathologic effects on the liver and kidneys was observed. No protective effects were observed in the testes for either of the 2 studied antioxidants. In conclusion, hesperidin and lipoic acid provided protective effects against As(III)-induced acute toxicity in the liver and kidneys of mice. These compounds may potentially play an important role in the protection of populations chronically exposed to arsenic.

Animals↗
PubMedDate not supplied

[Lipoic acid as a means of metabolic therapy of open-angle glaucoma].

A total of 45 patients (90 eyes) with stages I and II open-angle glaucoma (OAG) were examined, 26 of these were administered lipoic acid in a daily dose of 0.075 g for 2 months and 19 were given 0.15 g daily for 1 month. Control group consisted of 31 patients with OAG who were administered only local hypotensive therapy. Vision acuity and visual field were checked up, tonometry, tonography, and campimetry carried out, and levels of nonprotein SH-groups and activity of gamma-glutamyl transpeptidase measured in the lacrimal fluid. Improvement of the biochemical parameters, visual function, and of the coefficient of efficacy of liquid discharge was more expressed in the patients administered lipoic acid in a daily dose of 0.15 g. Color campimetry results indicate improved sensitivity of the visual analyzer under the effect of treatment. Improvement was attained in approximately 45-47.5% of examined eyes, and was more often seen in patients with stage II OAG: in 57-58% eyes. The effect of lipoic acid may be explained by its antioxidant properties and direct influence on ocular tissue metabolism.

Aged↗
PubMed2001

Lipoic acid improves survival in transgenic mouse models of Huntington's disease.

There is substantial evidence implicating excitotoxicity and oxidative damage in the pathogenesis of Huntington's disease (HD). We therefore examined whether the antioxidants 2-sulpho-tert-phenyibutyinitrone (S-PBN) and alpha-lipoic acid could exert neuroprotective effects in transgenic mouse models of HD. S-PBN showed no effects on either weight loss or survival in the R6/2 transgenic HD mice. alpha-Lipoic acid produced significant increases in survival in both R6/2 and N171-82Q transgenic mouse models of HD. These findings suggest that alpha-lipoic acid might have beneficial effects in HD patients.

Animals↗
PubMed2006

Mitochondrial membrane damage during aging process in rat heart: potential efficacy of L-carnitine and DL alpha lipoic acid.

Mitochondria are the main intracellular source of oxidizing free radicals and these oxidants produced exhibit selectivity in damaging mitochondrial macromolecules and membrane functions. In the present study we have investigated the effect of co-supplementation of carnitine (300 mg/kg bw) and lipoic acid (100 mg/kg bw) for 28 days in young, middle aged and aged rats and evaluated the effect of these compounds on age-related alterations in mitochondrial membrane functions. The levels of H2O2 were increased in both middle aged and aged rats with a concomitant decrease in the levels of cardiolipin and mitochondrial membrane potential. The levels of membrane bound ATPases were also decreased in aged rats along with alterations in mitochondrial morphology. Supplementation of carnitine and lipoic acid to middle aged and aged rats brought these changes to near normalcy. Thus, lipoic acid acts with carnitine to improve mitochondrial-supported bioenergetics and also improves general antioxidant status, thereby effectively attenuating any putative increase in oxidative stress with age.

Aging↗
PubMed2005

Effects of alpha-lipoic acid on kinin B1 and B2 receptor binding sites in the spinal cord of chronically angiotensin-treated rats.

A quantitative autoradiographic study was performed to determine whether kinin receptors are altered in the rat spinal cord in an experimental model of arterial hypertension under antioxidant therapy with alpha-lipoic acid. Sprague-Dawley rats were fed for 4 weeks with a normal chow diet or with an alpha-lipoic acid supplemented diet (1000 mg/kg feed), and treated for the last 2 weeks with angiotensin II (AT II) (200 ng/kg/min with an osmotic pump implanted s.c.). Control rats received either diet but not AT II. A 2-week administration of AT II increased significantly systolic blood pressure, the production of superoxide anion in the aorta and B1 receptor binding sites in the thoracic spinal dorsal horn. This treatment did not affect spinal B2 receptor binding sites, glycemia and insulinemia. The diet supplemented with alpha-lipoic acid reduced significantly the increase in systolic blood pressure, the production of aortic superoxide anion and prevented the increases of B1 receptor binding sites. Results show an association between the oxidative stress and the increases of B1 receptors and arterial blood pressure induced by AT II. Data also exclude the possibility that arterial hypertension is a primary mechanism leading to an increase of B2 receptor binding sites in the rat spinal cord.

Angiotensin II↗
PubMed1997

Modulation of cellular reducing equivalent homeostasis by alpha-lipoic acid. Mechanisms and implications for diabetes and ischemic injury.

The therapeutic potential of alpha-lipoic acid (thioctic acid) was evaluated with respect to its influence on cellular reducing equivalent homeostasis. The requirement of NADH and NADPH as cofactors in the cellular reduction of alpha-lipoic acid to dihydrolipoate has been reported in various cells and tissues. However, there is no direct evidence describing the influence of such reduction of alpha-lipoate on the levels of cellular reducing equivalents and homeostasis of the NAD(P)H/NAD(P) ratio. Treatment of the human Wurzburg T-cell line with 0.5 mM alpha-lipoate for 24 hr resulted in a 30% decrease in cellular NADH levels. alpha-Lipoate treatment also decreased cellular NADPH, but this effect was relatively less and slower compared with that of NADH. A concentration-dependent increase in glucose uptake was observed in Wurzburg cells treated with alpha-lipoate. Parallel decreases (30%) in cellular NADH/NAD+ and in lactate/pyruvate ratios were observed in alpha-lipoate-treated cells. Such a decrease in the NADH/NAD+ ratio following treatment with alpha-lipoate may have direct implications in diabetes, ischemia-reperfusion injury, and other pathologies where reductive (high NADH/NAD+ ratio) and oxidant (excess reactive oxygen species) imbalances are considered as major factors contributing to metabolic disorders. Under conditions of reductive stress, alpha-lipoate decreases high NADH levels in the cell by utilizing it as a co-factor for its own reduction process, whereas in oxidative stress both alpha-lipoate and its reduced form, dihydrolipoate, may protect by direct scavenging of free radicals and recycling other antioxidants from their oxidized forms.

Cells, Cultured↗
PubMed1997

Influence of selegiline and lipoic acid on the life expectancy of immunosuppressed mice.

Ten groups of 14 immunosuppressed NMRI-mice (nu/nu) were raised and kept under germ-reduced conditions. The control animals were fed a germ-reduced diet, nine other groups received the same diet with selegiline (CAS 14611-51-9, Deprenyl) or lipoic acid (thioctic acid, CAS 62-46-4) admixed at various amounts. The 50% survival rate, the total life span of each group and the areas under the curves were determined to evaluate life expectancy as compared to the controls. The racemate of lipoic acid at high dosage (350 mg/kg body weight) reduced the life span significantly. The S(-)-enantiomer of lipoic acid (75 mg/kg body weight) increased the 50% survival rate, whereas the physiologic R(+)-enantiomer (9 mg/kg body weight) expanded the total life span of its group. Alteration of only one out of three parameters was not considered significant. All other groups except for one did not differ from controls: only animals which obtained 75 micrograms selegiline per kg of body weight and per day exerted increased life expectancies by all three parameters. This group exhibited also in statistical evaluation a significantly (p < 0.05) prolongated survival time up to about 200% as compared to the control animals.

Animals↗