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Lipoic Acid (lipoic + acid)

Distribution by Scientific Domains

Medical Sciences	48%
Life Sciences	41%
Chemistry	10%

Distribution within Medical Sciences

Diabetes	27%
Dermatology	20%

Selected Abstracts

A Facile Regioselective Decomposition of Tosylhydrazones: An Application Towards the Synthesis of ,-Lipoic Acid (IX).

CHEMINFORM, Issue 41 2005
Subhash P. Chavan
No abstract is available for this article. [source]

,-Lipoic acid reduces congenital malformations in the offspring of diabetic mice

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 3 2009
Y. Sugimura
Abstract Background The mechanism of diabetes-induced congenital malformation remains to be elucidated. It has been reported that ,-lipoic acid (LA) prevents neural tube defects (NTDs) in offsprings of rats with streptozotocin-induced diabetes. Here, we evaluate the protective effect of LA against diabetic embryopathy, including NTDs, cardiovascular malformations (CVMs), and skeletal malformations, in mice. Methods Female mice were rendered hyperglycemic using streptozotocin and then mated with normal male mouse. Pregnant diabetic or non-diabetic mice were treated daily with either LA (100 mg/kg body weight) or saline between gestational days 0 and 18. On day 18, fetuses were examined for congenital malformations. Results Plasma glucose levels on day 18 were not affected by LA treatment. No congenital malformations were observed either in the saline-treated or LA-treated non-diabetic group. In the saline-treated diabetic group, 39% of fetuses had external malformations and 30% had NTDs. In the LA-treated diabetic group, the corresponding proportions were 11 and 8%, respectively. LA treatment also decreased the incidence of CVMs from 30,3% and of skeletal malformations from 29,6%. Conclusions We conclude that LA can reduce NTDs, CVMs and skeletal malformations in the offspring of diabetic mice at term delivery. Copyright © 2009 John Wiley & Sons, Ltd. [source]

The effect of biothiol on UV irradiated ,-lipoic acid

BIOFACTORS, Issue 4 2008
Naoki Wada
Abstract ,-Lipoic acid (LA) and its reduced form dihydrolipoic acid (DHLA) are well known as strong antioxidants. LA has the characteristic distorted five membered 1,2-dithiolane ring, which is quite vulnerable to UV irradiation. The UV induced decomposition of LA and the effect of the following addition of biothiols to the photoirradiated solution of LA were investigated by UV-vis spectrometry and 1H NMR spectral analysis. The mechanism of UV irradiated LA decomposition was proposed based on the results obtained from NMR and GPC measurements. [source]

,-Lipoic acid reduces congenital malformations in the offspring of diabetic mice

Treatment of symptomatic diabetic polyneuropathy with the antioxidant ,-lipoic acid: a meta-analysis

DIABETIC MEDICINE, Issue 2 2004
D. Ziegler
Abstract Aims To determine the efficacy and safety of 600 mg of ,-lipoic acid given intravenously over 3 weeks in diabetic patients with symptomatic polyneuropathy. Methods We searched the database of VIATRIS GmbH, Frankfurt, Germany, for clinical trials of ,-lipoic acid according to the following prerequisites: randomized, double-masked, placebo-controlled, parallel-group trial using ,-lipoic acid infusions of 600 mg i.v. per day for 3 weeks, except for weekends, in diabetic patients with positive sensory symptoms of polyneuropathy which were scored by the Total Symptom Score (TSS) in the feet on a daily basis. Four trials (ALADIN I, ALADIN III, SYDNEY, NATHAN II) comprised n = 1258 patients (,-lipoic acid n = 716; placebo n = 542) met these eligibility criteria and were included in a meta-analysis based on the intention-to-treat principle. Primary analysis involved a comparison of the differences in TSS from baseline to the end of i.v. Treatment between the groups treated with ,-lipoic acid or placebo. Secondary analyses included daily changes in TSS, responder rates (, 50% improvement in TSS), individual TSS components, Neuropathy Impairment Score (NIS), NIS of the lower limbs (NIS-LL), individual NIS-LL components, and the rates of adverse events. Results After 3 weeks the relative difference in favour of ,-lipoic acid vs. placebo was 24.1% (13.5, 33.4) (geometric mean with 95% confidence interval) for TSS and 16.0% (5.7, 25.2) for NIS-LL. The responder rates were 52.7% in patients treated with ,-lipoic acid and 36.9% in those on placebo (P < 0.05). On a daily basis there was a continuous increase in the magnitude of TSS improvement in favour of ,-lipoic acid vs. placebo which was noted first after 8 days of treatment. Among the individual components of the TSS, pain, burning, and numbness decreased in favour of ,-lipoic acid compared with placebo, while among the NIS-LL components pin-prick and touch-pressure sensation as well as ankle reflexes were improved in favour of ,-lipoic acid after 3 weeks. The rates of adverse events did not differ between the groups. Conclusions The results of this meta-analysis provide evidence that treatment with ,-lipoic acid (600 mg/day i.v.) over 3 weeks is safe and significantly improves both positive neuropathic symptoms and neuropathic deficits to a clinically meaningful degree in diabetic patients with symptomatic polyneuropathy. Diabet. Med. 21, 114,121 (2004) [source]

Enzymatic activation of sulfur for incorporation into biomolecules in prokaryotes

FEMS MICROBIOLOGY REVIEWS, Issue 6 2006
Dorothea Kessler
Abstract Sulfur is a functionally important element of living matter. Incorporation into biomolecules occurs by two basic strategies. Sulfide is added to an activated acceptor in the biosynthesis of cysteine, from which methionine, coenzyme A and a number of biologically important thiols can be constructed. By contrast, the biosyntheses of iron sulfur clusters, cofactors such as thiamin, molybdopterin, biotin and lipoic acid, and the thio modification of tRNA require an activated sulfur species termed persulfidic sulfur (R-S-SH) instead of sulfide. Persulfidic sulfur is produced enzymatically with the IscS protein, the SufS protein and rhodanese being the most prominent biocatalysts. This review gives an overview of sulfur incorporation into biomolecules in prokaryotes with a special emphasis on the properties and the enzymatic generation of persulfidic sulfur as well as its use in biosynthetic pathways. [source]

Transdermal delivery of two antioxidants from different cosmetic formulations

INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 1-2 2003
S. Richert
Synopsis The efficacy of any cosmetic product containing a functional ingredient is determined by the skin delivery of the active molecule, which is influenced by the type of the vehicle and the molecule itself. This study was designed to compare the percutaneous absorption habits of the antioxidants carcinine and lipoic acid out of various formulations by means of the porcine skin model. Initial evaluation of the in vitro porcine skin model has demonstrated its feasibility for various substances and formulations [1, 2]. Increasing legal requirements for risk assessment in the cosmetic industry have led to the development of this alternative test method. The penetration properties are determined by the OECD Guideline TG 428: Skin Absorption: in vitro Method [3, 4], which allows the use of porcine skin for penetration studies. Porcine skin is used because of its similarity to human skin in terms of its morphology and the essential permeation characteristics [5]. The mass balances for each tested formulation type of the antioxidants show individual penetration behaviours with significant differences. The presented data plainly demonstrate that the lipophilic lipoic acid has a distinct higher penetration potential than the hydrophilic carcinine. The chosen vehicle can enhance or reduce the transdermal delivery of both tested antioxidants. Modern effective cosmetic formulations will work only, if the active ingredients penetrate into the epidermis. In conclusion, the correct selection of a suitable formulation plays an important role during product development. Résumé L'efficacité d'un produit cosmétique ou de son principe actif est définie par l'absorption du principe actif par la peau. Cette action est influencée par la structure moléculaire du principe actif ainsi que par la galénique du produit. Dans cette étude, les taux d'absorption percutanée des agents anti-oxydants Carcinine et Acide Lipoïque intégrés dans différentes formulations cosmétiques ont été comparés avec le modèle de peau porcine. La phase de validation sur plusieurs années du modèle peau porcine in vitro a prouvé qu'il se prête très bien à la détermination de la pénétration percutanée de différentes substances et formulations. Des exigences légales de plus en plus sévères concernant la pratique des tests de sécurité pour les produits cosmétiques ont mené au développement de cette méthode qui remplace les essais sur animaux. La définition des qualités de pénétration se fait selon la directive OECD TG 428 : Skin Absorption : in vitro Method [3, 4] qui permet l'utilisation de la peau porcine provenant des abattoirs pour l'exécution des études de pénétration. Les bilans quantitatifs des formulations testées montrent que les agents anti-oxydants ont des comportements de pénétration différant de manière significative. Les données présentées démontrent très clairement que l'acide Lipoïque, lipophile, possède un potentiel de pénétration bien plus élevé que la Carcinine, hydrophile. La base cosmétique peut aussi réduire ou augmenter le potentiel de pénétration des agents anti-oxydant testés. En résumé, le choix correct d'un type de formulation joue un rôle très important dans le développement d'un produit cosmétique. [source]

Is ,-lipoic acid a scavenger of reactive oxygen species in vivo?

IUBMB LIFE, Issue 6 2008
Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity
Abstract The chemical reduction and oxidation (redox) properties of ,-lipoic acid (LA) suggest that it may have potent antioxidant potential. A significant number of studies now show that LA and its reduced form, dihydrolipoic acid (DHLA), directly scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) species and protect cells against a host of insults where oxidative stress is part of the underlying etiology. However, owing to its limited and transient accumulation in tissues following oral intake, the efficacy of nonprotein-bound LA to function as a physiological antioxidant has been questioned. Herein, we review the evidence that the micronutrient functions of LA may be more as an effector of important cellular stress response pathways that ultimately influence endogenous cellular antioxidant levels and reduce proinflammatory mechanisms. This would promote a sustained improvement in cellular resistance to pathologies where oxidative stress is involved, which would not be forthcoming if LA solely acted as a transient ROS scavenger. © 2008 IUBMB IUBMB Life, 60(6): 362,367, 2008 [source]

Combined R-,,lipoic acid and acetyl-L-carnitine exerts efficient preventative effects in a cellular model of Parkinson's disease

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1-2 2010
Hongyu Zhang
Abstract Mitochondrial dysfunction and oxidative damage are highly involved in the pathogenesis of Parkinson's disease (PD). Some mitochondrial antioxidants/nutrients that can improve mitochondrial function and/or attenuate oxidative damage have been implicated in PD therapy. However, few studies have evaluated the preventative effects of a combination of mitochondrial antioxidants/nutrients against PD, and even fewer have sought to optimize the doses of the combined agents. The present study examined the preventative effects of two mitochondrial antioxidant/nutrients, R-,,lipoic acid (LA) and acetyl-L-carnitine (ALC), in a chronic rotenone-induced cellular model of PD. We demonstrated that 4-week pretreatment with LA and/or ALC effectively protected SK-N-MC human neuroblastoma cells against rotenone-induced mitochondrial dysfunction, oxidative damage and accumulation of ,-synuclein and ubiquitin. Most notably, we found that when combined, LA and ALC worked at 100,1000-fold lower concentrations than they did individually. We also found that pretreatment with combined LA and ALC increased mitochondrial biogenesis and decreased production of reactive oxygen species through the up-regulation of the peroxisome proliferator-activated receptor-, coactivator 1, as a possible underlying mechanism. This study provides important evidence that combining mitochondrial antioxidant/nutrients at optimal doses might be an effective and safe prevention strategy for PD. [source]

Gene expression profiling of aging in multiple mouse strains: identification of aging biomarkers and impact of dietary antioxidants

AGING CELL, Issue 4 2009
Sang-Kyu Park
Summary We used DNA microarrays to identify panels of transcriptional markers of aging that are differentially expressed in young (5 month) and old (25 month) mice of multiple inbred strains (129sv, BALB/c, CBA, DBA, B6, C3H and B6C3F1). In the heart, age-related changes of five genes were studied throughout the mouse lifespan: complement component 4, chemokine ligand 14, component of Sp100-rs, phenylalanine hydroxylase and src family associated phosphoprotein 2. A similar analysis in the brain (cerebellum) involved complement component 1q (alpha polypeptide), complement component 4, P lysozyme structural, glial fibrillary acidic protein and cathepsin S. Caloric restriction (CR) inhibited age-related expression of these genes in both tissues. Parametric analysis of gene set enrichment identified several biological processes that are induced with aging in multiple mouse strains. We also tested the ability of dietary antioxidants to oppose these transcriptional markers of aging. Lycopene, resveratrol, acetyl- l -carnitine and tempol were as effective as CR in the heart, and ,-lipoic acid and coenzyme Q10 were as effective as CR in the cerebellum. These findings suggest that transcriptional biomarkers of aging in mice can be used to estimate the efficacy of aging interventions on a tissue-specific basis. [source]

REVIEW: Vitamin transport and homeostasis in mammalian brain: focus on Vitamins B and E

JOURNAL OF NEUROCHEMISTRY, Issue 2 2007
Reynold Spector
Abstract With the application of genetic and molecular biology techniques, there has been substantial progress in understanding how vitamins are transferred across the mammalian blood,brain barrier and choroid plexus into brain and CSF and how vitamin homeostasis in brain is achieved. In most cases (with the exception of the sodium-dependent multivitamin transporter for biotin, pantothenic acid, and lipoic acid), the vitamins are transported by separate carriers through the blood,brain barrier or choroid plexus. Then the vitamins are accumulated by brain cells by separate, specialized systems. This review focuses on six vitamins (B1, B3, B6, pantothenic acid, biotin, and E) and the newer genetic information including relevant ,knockdown' or ,knockout' models in mice and humans. The overall objective is to integrate this newer information with previous physiological and biochemical observations to achieve a better understanding of vitamin transport and homeostasis in brain. This is especially important in view of the newly described non-cofactor vitamin roles in brain (e.g. of B1, B3, B6, and E) and the potential roles of vitamins in the therapy of brain disorders. [source]

Altered arachidonic acid biosynthesis and antioxidant protection mechanisms in Schwann cells grown in elevated glucose

JOURNAL OF NEUROCHEMISTRY, Issue 6 2002
Cristinel Mîinea
Abstract In cultured Schwann cells, elevated glucose induces alterations in arachidonic acid metabolism that cause a decrease in the content of glycerophospholipid arachidonoyl-containing molecular species (ACMS). This could result from decreased de novo arachidonic acid biosynthesis, or increased arachidonic acid release from phospholipids. Incorporation of radioactive 8,11,14-eicosatrienoic acid into ACMS was lower for cells grown in 30 mm versus 5 mm glucose, consistent with a decrease in ,5 desaturase activity. However, neither basal arachidonic acid release from prelabeled cells nor stimulated generation of arachidonic acid in the presence of the reacylation inhibitor, thimerosal, the phosphotyrosine phosphatase inhibitor, bipyridyl peroxovanadium, or both together, were altered by varying the glucose concentrations, indicating that arachidonic acid turnover did not contribute to ACMS depletion. Free cytosolic NAD+/NADH decreased, whereas NADP+/NADPH remained unchanged for cells grown in elevated glucose, implying that decreased desaturase activity is a result of metabolic changes other than cofactor availability. Schwann cells in elevated glucose were susceptible to oxidative stress, as shown by increased malondialdehyde, depleted glutathione levels, and reduced cytosolic superoxide dismutase activity. Glutathione-altering compounds had no effect on ACMS levels, in contrast to N -acetylcysteine and ,-lipoic acid, which partly corrected ACMS depletion in phosphatidylcholine. These findings suggest that in the Schwann cell cultures, a high glucose level elicits oxidative stress and weakens antioxidant protection mechanisms which could decrease arachidonic acid biosynthesis and that this deficit can be partly corrected by treatment with exogenous antioxidants. [source]

Bioenergetics in the pathogenesis of neurodegeneration

JOURNAL OF NEUROCHEMISTRY, Issue 2001
M. Flint Beal
Evidence implicating both mitochondria and bioenergetics as playing a crucial role in necrotic and apoptotic cell death is rapidly accumulating. Mitochondria are essential in controlling specific apoptosis cell death pathways and they are the major source of free radicals in the cell. Direct evidence for a role of mitochondria in neurodegenerative diseases comes from studies in Friedreich's Ataxia. Mutations in frataxin lead to an accumulation of iron within mitochondria. We found a three-fold increase in a marker of oxidative damage to DNA in the urine of patients with Friedreich's Ataxia. There is evidence for mitochondrial defects in patients with amyotrophic lateral sclerosis (ALS). There are mitochondrial abnormalities in liver biopsies and muscle biopsies from individuals with sporadic ALS. Muscle biopsies have shown reduced complex I activity in patients with sporadic ALS. A study of ALS cybrids showed a significant decrease in complex I activity as well as trends towards reduced complex 3 and 4 activities. We found increased levels of 8-hydroxy-2-deoxyguanosine, a marker of oxidative damage to DNA in the plasma, urine and CSF of sporadic ALS patients and increased numbers of point mutations in mtDNA of ALS spinal cord tissue. There is mitochondrial vacuolization in transgenic mouse models of ALS. We found substantial evidence for mitochondrial dysfunction in Huntington's Disease (HD). In HD postmortem brain tissue, there are significant reductions in complex 2, 3 activity. We also demonstrated increased brain lactate concentrations as well as reduced phosphocreatine to inorganic phosphate ratio in the resting muscle of patients with HD. More recent studies have demonstrated that there is abnormal depolarization of mitochondria of HD lymphoblasts, which directly correlates with CAG repeat length. There are reductions in ATP production in muscle are both presymptomatic and symptomatic HD patients. Transgenic mouse models of HD show significant reductions in N-acetylaspartate concentrations, which precede the onset of neuronal degeneration. We investigated a number of therapeutic interventions in both transgenic mouse models of ALS and HD. In transgenic ALS mice we found that oral administration of creatine dose-dependently extends survival and reduces the neuronal degeneration in the spinal cord. We found modest protection with ginkgo biloba and lipoic acid. In the HD mice we found significant improvement with oral administration of creatine in two different transgenic mouse models. Creatine not only extended survival but it also improved motor performance, delayed weight loss and attenuated striatal atrophy. Creatine significantly attenuated reductions in N-acetylaspartate concentrations as assessed using magnetic resonance spectroscopy. We also found significant neuroprotective effects with dichloroacetate, which stimulates pyruvate dehydrogenase. These findings implicate bioenergetic dysfunction in transgenic mouse models of both ALS and HD, and they suggest several novel therapeutic strategies aimed at energy replenishment. [source]

Alpha lipoic acid in burning mouth syndrome , a randomized double-blind placebo-controlled trial

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 3 2009
Desirée Rosa Cavalcanti
The burning mouth syndrome (BMS) is a chronic condition characterized by oral burning pain in the absence of clinical abnormalities and without established therapy. Objectives:, The purpose of this study was to evaluate the effectiveness of alpha lipoic acid (ALA) in the management of BMS symptoms through a randomized double-blind placebo-controlled trial. Methods:, Thirty-eight patients (34 women and four men, median age 62.9 years, range 36,78) were included and 31 completed the study. The patients were randomized into two cycles of treatment: one with alpha lipoic acid and one with placebo both administered in identical capsules. These cycles were separated by a washout period of 20 days. The oral symptoms and the treatment response were assessed using a 100-mm visual analog scale before and after each cycle and the global perceived effect score, using a 5-point scale after each treatment cycle. Results:, The level of reduction on burning was significant for both treatments (paired t -test: P < 0.05; rp = 0.011; ral < 0.001). Considering the two cycles together, 22 patients reported at least some improvement after ALA use and 23 patients after placebo. Conclusions:, Comparison of the oral assessment scores of the two cycles failed to demonstrate the effectiveness of ALA over placebo (t -test: P > 0.05; r = 0.75). [source]

LplA1-dependent utilization of host lipoyl peptides enables Listeria cytosolic growth and virulence

MOLECULAR MICROBIOLOGY, Issue 3 2007
Kristie M. Keeney
Summary The bacterial pathogen Listeria monocytogenes replicates within the cytosol of mammalian cells. Mechanisms by which the bacterium exploits the host cytosolic environment for essential nutrients are poorly defined. L. monocytogenes is a lipoate auxotroph and must scavenge this critical cofactor, using lipoate ligases to facilitate attachment of the lipoyl moiety to metabolic enzyme complexes. Although the L. monocytogenes genome encodes two putative lipoate ligases, LplA1 and LplA2, intracellular replication and virulence require only LplA1. Here we show that LplA1 enables utilization of host-derived lipoyl peptides by L. monocytogenes. LplA1 is dispensable for growth in the presence of free lipoate, but necessary for growth on low concentrations of mammalian lipoyl peptides. Furthermore, we demonstrate that the intracellular growth defect of the ,lplA1 mutant is rescued by addition of exogenous lipoic acid to host cells, suggesting that L. monocytogenes dependence on LplA1 is dictated by limiting concentrations of available host lipoyl substrates. Thus, the ability of L. monocytogenes and other intracellular pathogens to efficiently use host lipoyl peptides as a source of lipoate may be a requisite adaptation for life within the mammalian cell. [source]

Homocysteine-lowering therapy or antioxidant therapy for bone loss in Parkinson's disease,

MOVEMENT DISORDERS, Issue 3 2010
Seung Hun Lee MD
Abstract We investigated whether homocysteine (Hcy)- lowering therapy or an antioxidant prevented bone loss in Parkinson's disease (PD) patients taking levodopa. Forty-two PD patients with low bone mineral density (BMD) taking levodopa were randomly assigned to Hcy-lowering therapy (5 mg folate and 1500 ,g vitamin B12 daily), ,-lipoic acid (,-LA) therapy (1200 mg daily), or control groups. Primary outcomes were BMD changes from baseline to 12 months. Secondary outcomes were changes in Hcy level, and C-telopeptide (CTX) levels at 12 months. Forty-one patients completed the study. Hcy-lowering therapy resulted in significantly greater BMD changes at the lumbar spine (4.4%), total femur (2.8%), and femur shaft (2.8%) than control (P = 0.005,0.023). BMD changes in the ,,LA therapy group were similar to those of the control group, but changes at the trochanter (4.6%) were significantly greater in the ,,LA therapy group than in the control group after adjustment for body mass index changes. Hcy concentrations decreased to 35.2% ± 13.4% in the Hcy-lowering therapy group, but increased in other groups. Serum CTX levels at 12 months tended to be lower in the Hcy-lowering group (0.442 ± 0.024 ng/mL) than control group (0.628 ± 0.039 ng/mL) (P = 0.159). This small trial suggests that Hcy-lowering therapy may prevent bone loss in PD patients taking levodopa. © 2009 Movement Disorder Society [source]

Protective effect of green tea polyphenol (-)-epigallocatechin gallate and other antioxidants on lipid peroxidation in gerbil brain homogenates

PHYTOTHERAPY RESEARCH, Issue 3 2003
Seong-Ryong Lee
Abstract The aim of this study was to compare the protective effects of green tea polyphenol (-)-epigallocatechin gallate (EGCG) and other well-known antioxidants on the lipid peroxidation in gerbil brain homogenates. Oxidative stress was induced by H2O2 (10 mM) or ferrous ammonium sulfate (5 µM) and lipid peroxidation was studied. Hydrogen peroxide and ferrous ions are capable of oxidizing a wide range of substrates and causing biological damage. The reaction, referred to as the Fenton process, is complex and can generate both hydroxyl radicals and higher oxidation states of the iron. Thiobarbituric acid-reactive substances (TBA-RS) were used as a marker of lipid peroxidation. EGCG, trolox, lipoic acid, and melatonin reduced H2O2 - or ferrous ion-induced lipid peroxidation in a concentration-dependant manner. In reducing the H2O2 -induced lipid peroxidation, IC50 values of antioxidants were as follows: EGCG (0.66 µM), trolox (37.08 µM), lipoic acid (7.88 mM), and melatonin (19.11 mM). In reducing the ferrous ion-induced lipid peroxidation, IC50 values of antioxidants were as follows: EGCG (3.32 µM), trolox (75.65 µM), lipoic acid (7.63 mM), and melatonin (15.48 mM). Under the in vitro conditions of this experiment, EGCG was the most potent antioxidant in inhibiting H2O2 or ferrous ion-induced lipid peroxidation in the gerbil brain homogenates. Copyright © 2003 John Wiley & Sons, Ltd. [source]

Ibuprofen and Lipoic Acid Diamides as Potential Codrugs with Neuroprotective Activity

ARCHIV DER PHARMAZIE, Issue 3 2010
Piera Sozio
Abstract Current evidences support the hypothesis that non-steroidal anti-inflammatory drugs (NSAIDs) and antioxidant therapy might protect against the development of Alzheimer's disease (AD). In the present work, our attention was focused on ibuprofen (IBU) used in clinical trails to prevent Alzheimer's disease, and (R)-,-lipoic acid (LA) considered as a potential neuroprotective agent in AD therapy. In particular, we investigated a series of lipophilic molecular combinations obtained by joining (R)-,-lipoic acid and ibuprofen via an amide bond. These new entities might allow targeted delivery of the parent drugs to neurons, where cellular oxidative stress and inflammation seem related to Alzheimer's disease. Our study included the synthesis of conjugates 1,3 and the evaluation of their physicochemical and in-vitro antioxidant properties. The new compounds are extremely stable in aqueous buffer solutions (pH = 1.3 and 7.4), and in rat and human plasma they showed a slow bioconversion to ibuprofen and (R)-,-lipoic acid. Codrugs 1,3 displayed in vitro free radical scavenging activity and were hydrolyzed more rapidly in brain tissue than in rat serum indicating that these new entities might allow targeted delivery of the parent drugs to neurons. The immunohistochemical analysis of A, (1-40) protein showed that A,-injected cerebral cortices treated with ibuprofen or compound 1 showed few plaques within capillary vessels and, in particular, A, (1-40) protein was less expressed in codrug- 1 -treated than in ibuprofen-treated cerebral cortex. [source]

The effect of biothiol on UV irradiated ,-lipoic acid

Redox regulation of mitochondrial permeability transition: Effects of uncoupler, lipoic acid and its positively charged analog LA-plus and selenium,

BIOFACTORS, Issue 1-4 2003
Oren Tirosh
First page of article [source]

Antioxidants modulate the IL-6 induced inhibition of negative acute-phase protein secretion in HepG2 cells

CELL BIOCHEMISTRY AND FUNCTION, Issue 1 2008
Mohamed A. El-Saadany
Abstract Despite increasing evidence on the potential of dietary antioxidants in modulating the etiology of certain chronic diseases such as cancer and cardiovascular diseases, little is known about their beneficial role in acute-phase responses and inflammatory diseases. From this viewpoint the aim of this study was to investigate the effect of selected dietary antioxidants in modulating the secretion of negative acute-phase proteins caused by interleukin-6 (IL-6) in HepG2 cells. Cells were first stimulated with a fixed dose of IL-6 for 24,h then incubated for a further 8,h with varying concentrations of eight antioxidants, ,-lipoic acid (LA), (,)-epicatechin (EC), (,)-epicatechin gallate (ECG), (,)-epigallocatechin (EGC), (,)-epigallocatechin gallate (EGCG), ,-tocopherol (TOC), ascorbic acid (AA) and N-acetylcysteine (NAC). The culture supernatants were assayed for transthyretin (TTR) and retinol binding protein (RBP) using ELISA. The data revealed that IL-6 significantly reduced TTR and RBP secretion compared with the basal production. All tested antioxidants attenuate the reduction in TTR and RPB levels. The strongest effects were achieved with the highest concentration of each antioxidant. The order of effect were LA,>,EGCG,>,ECG,>,TOC,>,EGC,>,EC,>,NAC,>,AA. In conclusion, these results provide evidence that the dietary antioxidants can play a fundamental role in inflammatory processes. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Support for the idea that light is a risk factor in optic neuropathies, like glaucoma

ACTA OPHTHALMOLOGICA, Issue 2007
NN OSBORNE
Purpose: Retinal ganglion cell (RGC) axons in the globe contain many mitochondria and it has been hypothesised that light can interact with these organelles to affect RGC survival in glaucoma. Studies on different cell-types were conducted to support such a proposition. Methods: Near confluent cultures of RGC-5 cells, primary rat retinal cultures, fibroblasts with normal (BJhTERT) or mitochondria depleted of mtDNA (rho0) were transferred to incubators containing light (400-760nm; 800-2000 lux; generally 2 days). Some of the cultures were covered with white paper to exclude the light. The cultures were then analysed for cell viability, generation of free radicals (ROS) and for death by apoptosis. Results: Oxidative status and mitochondrial dehydrogenase activity in retinal cultures (-40±5%), RGC-5 cells (-20±4%) and BJhTERT cells (-13±3%) was reduced significantly by light. Light reduced the number of GABA-positive neurones (-42±6%) in retinal cultures. Light caused a 3-5 fold increase in TUNEL-positive cells in primary retinal, RGC-5 and BJhTERT cultures, than in the dark. ROS staining was also clearly elevated by light. The light-induced toxic effect on the different cell types was significantly blunted by antioxidants like vitamin E and lipoic acid. Moreover, light-induced apoptosis was caspase independent but PARP dependent. In contrast, rho0 cells that lacked functional mitochondria were unaffected by light. Conclusions: The present study shows that light can directly affect mitochondrial function to induce apoptosis. This supports the view that light can interact with the many RGC axon mitochondria to affect the viability of GCs and that this may be of significance in the progression of glaucoma. [source]

Multi-tasking with Single Platform Dendrimers for Targeting Sub-Cellular Microenvironments

CHEMISTRY - A EUROPEAN JOURNAL, Issue 21 2010
Rami Hourani
Double trouble! Orthogonally functionalised dendrimers have been constructed by using a versatile approach that is widely applicable for therapeutics and diagnostics by combining imaging agents and therapeutics for synergistic effects. Dendrimers containing a covalently linked dipyrromethene boron difluoride (BODIPY) dye and ,-lipoic acid perform complementary biological functions and target intracellular lipid droplets (see figure). [source]

Antioxidants and narrow band-UVB in the treatment of vitiligo: a double-blind placebo controlled trial

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 6 2007
M. L. Dell'Anna
Summary Background., Vitiligo is an acquired depigmenting disease with uncertain aetiopathogenesis, possibly associated with oxidative stress. Narrowband ultraviolet B phototherapy (NB-UVB) is the most widely used and effective treatment. Aim., To evaluate the clinical effectiveness of NB-UVB and the repairing of oxidative stress-induced damage, using oral supplementation with an antioxidant pool (AP). Methods., Patients (n = 35) with nonsegmental vitiligo were enrolled in a randomized, double-blind, placebo-controlled multicentre trial. The treatment group received, for 2 months before and for 6 months during the NB-UVB treatment, a balanced AP containing ,-lipoic acid, vitamins C and E, and polyunsaturated fatty acids. The area and number of lesions, as well as some parameters of the oxidation,reduction (redox) status of the peripheral blood mononuclear cells (PBMCs) were estimated at the beginning, after 2 months, and at the end of the trial. Results., In total, 28 patients completed the study. After 2 months of AP supplementation, the catalase activity and the production of reactive oxygen species (ROS) were 121% and 57% of the basal values (P < 0.05 and P < 0.02 vs. placebo, respectively). The AP increased the therapeutic success of NB-UVB, with 47% of the patients obtaining >,75% repigmentation vs. 18% in the placebo group (P < 0.05). An increase in catalase activity to 114% (P < 0.05 vs. placebo) and decrease in ROS level of up to 60% (P < 0.02 vs. placebo) of the basal value was observed in PBMCs. Finally, the AP intake maintained the membrane lipid ratio (saturated : unsaturated fatty acids 1.8 : 3.1; P < 0.05), counteracting phototherapy-induced saturation. Conclusions., Oral supplementation with AP containing ,-lipoic acid before and during NB-UVB significantly improves the clinical effectiveness of NB-UVB, reducing vitiligo-associated oxidative stress. [source]