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PubMed2007

Beneficial effect of DL-alpha-lipoic acid on cyclosporine A induced hyperlipidemic nephropathy in rats.

Cyclosporine A (CsA)-induced dyslipidemia is one of the most important risk factors for morbidity and mortality after solid organ transplantation. Reducing this side effect of CsA by dietary agents may be safe, cost-effective, and attractive to both patients and health professionals. Hence the present study was designed to evaluate the role of DL-alpha-Lipoic acid (LA) in deteriorating the lipid abnormalities induced by CsA in rat kidney. Male albino Wistar rats were divided into four groups. CsA administered at a dose of 25 mg/kg body weight, orally for 21 days showed abnormal changes in the levels of lipoprotein fractions (LDL, HDL and VLDL) and lipid profile in both plasma and renal tissue. Significant alterations were also observed in the activities of lipid metabolizing enzymes. Co-treatment with LA (20 mg/kg body weight, oral gavage, for 21 days) reverted the levels of lipid profile (P < 0.001, P < 0.01) and lipoprotein fractions (P < 0.001, P < 0.01) to near control. The activities of lipid metabolizing enzymes also showed considerable restoration on LA supplementation. The outcome of this study provides evidence that LA (a natural metabolic antioxidant) treatment acts as a potent antilipemic agent against CsA-induced lipid abnormalities.

Animals↗
PubMed2006

Role of lipoic acid in reducing the oxidative stress induced by cyclosporine A.

BACKGROUND: Cyclosporine A (CsA) is the first choice immunosuppressant universally used for the prevention of allograft rejection in solid organ transplantation and immune-mediated diseases. However, with increasing use, evidence has accumulated that CsA therapy is associated with a variety of side effects, the most important being nephrotoxicity. We investigated the potential role of DL-alpha lipoic acid (LA), a universal antioxidant in combating the oxidative stress induced by CsA. METHODS: Adult male albino Wistar rats were divided into 4 treatment groups. Two groups received CsA (25 mg/kg body weight, orally for 21 days) to induce nephrotoxicity. One of these groups received LA treatment (20 mg/kg body weight, orally) for 21 days concurrently during CsA administration. A vehicle treated control group and a LA drug control were also included. RESULTS: CsA-induced nephrotoxicity was assessed in terms of increased activities of serum marker enzymes; alkaline phosphatase, acid phosphatase and lactate dehydrogenase. An apparent rise in the activities of N-acetyl-beta-D-glucosaminidase, beta-glucuronidase and cathepsin D were seen in the renal tissue of CsA given rats, which were reversed upon treatment with LA. CsA administration induced significant elevation in lipid peroxidation along with abnormal levels of enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase) and non-enzymic antioxidants (glutathione, vitamins C and E) in the rat kidney. LA administration improved renal function, by bringing about a significant decrease in peroxidative levels and increase in antioxidant status. CONCLUSION: These results indicate that LA has a protective action against CsA nephrotoxicity and suggest that the LA may find clinical application against a variety of toxins where cellular damage is a consequence of reactive oxygen species.

Animals↗
PubMed1996

The antioxidant alpha-lipoic acid enhances insulin-stimulated glucose metabolism in insulin-resistant rat skeletal muscle.

Insulin resistance of muscle glucose metabolism is a hallmark of NIDDM. The obese Zucker (fa/fa) rat--an animal model of muscle insulin resistance--was used to test whether acute (100 mg/kg body wt for 1 h) and chronic (5-100 mg/kg for 10 days) parenteral treatments with a racemic mixture of the antioxidant alpha-lipoic acid (ALA) could improve glucose metabolism in insulin-resistant skeletal muscle. Glucose transport activity (assessed by net 2-deoxyglucose [2-DG] uptake), net glycogen synthesis, and glucose oxidation were determined in the isolated epitrochlearis muscles in the absence or presence of insulin (13.3 nmol/l). Severe insulin resistance of 2-DG uptake, glycogen synthesis, and glucose oxidation was observed in muscle from the vehicle-treated obese rats compared with muscle from vehicle-treated lean (Fa/-) rats. Acute and chronic treatments (30 mg.kg-1.day-1, a maximally effective dose) with ALA significantly (P < 0.05) improved insulin-mediated 2-DG uptake in epitrochlearis muscles from the obese rats by 62 and 64%, respectively. Chronic ALA treatment increased both insulin-stimulated glucose oxidation (33%) and glycogen synthesis (38%) and was associated with a significantly greater (21%) in vivo muscle glycogen concentration. These adaptive responses after chronic ALA administration were also associated with significantly lower (15-17%) plasma levels of insulin and free fatty acids. No significant effects on glucose transporter (GLUT4) protein level or on the activities of hexokinase and citrate synthase were observed. Collectively, these findings indicate that parenteral administration of the antioxidant ALA significantly enhances the capacity of the insulin-stimulatable glucose transport system and of both oxidative and nonoxidative pathways of glucose metabolism in insulin-resistant rat skeletal muscle.

Animals↗
PubMed2006

Supply of R-alpha-lipoic acid and glutamine to casein-fed mice influences the number of B lymphocytes and tissue glutathione levels during endotoxemia.

BACKGROUND: An overwhelming production of reactive oxygen species concomitant with a decrease in antioxidative capacity plays an important role in modulation of the immune system in critically ill patients. The purpose of this study was to assess the influence of a combined oral supply of the antioxidants R-alpha-lipoic acid (LA) and glutamine (GLN) on the immunity of endotoxemic mice, with a special focus on tissue glutathione levels. METHODS: Female Balb/c mice were fed diets enriched with GLN (3 g/100 kcal), LA (0.74 mg/100 kcal), a combination of GLN and LA, or an isocaloric and isonitrogenous control diet for 10 days. On day 7, the mice were challenged intraperitoneally with 25 microg lipopolysaccharide. Seventy-two hours later, the number and phenotype of lymphocytes in Peyer's patches (PP) and spleen of the endotoxemic mice were measured. In addition, glutathione levels were determined in the small intestine, spleen and liver. RESULTS: In PP only the combined supply of GLN and LA significantly increased the total cell yield (+19%), which was predominantly due to an increased number of B cells. In the spleen, both LA (+17%) and the combination of GLN and LA (+22%) were able to enhance total cell yield. The glutathione content of the small intestine was increased by feeding LA alone, whereas in the spleen GLN plus LA was most effective. CONCLUSION: Supplying combined GLN and LA to endotoxemic mice is effective in selectively increasing the number of systemic and intestinal B lymphocytes. Furthermore, LA augmented the level of the main intracellular antioxidant glutathione in the small intestine. On the basis of these data we recommend investigation of the effects of LA and GLN supplementation in patients with sepsis.

Animals↗
PubMed2002

Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid.

Accumulation of oxidative damage to mitochondria, protein, and nucleic acid in the brain may lead to neuronal and cognitive dysfunction. The effects on cognitive function, brain mitochondrial structure, and biomarkers of oxidative damage were studied after feeding old rats two mitochondrial metabolites, acetyl-l-carnitine (ALCAR) [0.5% or 0.2% (wt/vol) in drinking water], and/or R-alpha-lipoic acid (LA) [0.2% or 0.1% (wt/wt) in diet]. Spatial memory was assessed by using the Morris water maze; temporal memory was tested by using the peak procedure (a time-discrimination procedure). Dietary supplementation with ALCAR and/or LA improved memory, the combination being the most effective for two different tests of spatial memory (P < 0.05; P < 0.01) and for temporal memory (P < 0.05). Immunohistochemical analysis showed that oxidative damage to nucleic acids (8-hydroxyguanosine and 8-hydroxy-2'-deoxyguanosine) increased with age in the hippocampus, a region important for memory. Oxidative damage to nucleic acids occurred predominantly in RNA. Dietary administration of ALCAR and/or LA significantly reduced the extent of oxidized RNA, the combination being the most effective. Electron microscopic studies in the hippocampus showed that ALCAR and/or LA reversed age-associated mitochondrial structural decay. These results suggest that feeding ALCAR and LA to old rats improves performance on memory tasks by lowering oxidative damage and improving mitochondrial function.

Acetylcarnitine↗
PubMed1996

Alpha-lipoic acid blocks HIV-1 LTR-dependent expression of hygromycin resistance in THP-1 stable transformants.

Gene expression of human immunodeficiency virus (HIV) depends on a host cellular transcription factors including nuclear factor-kappaB (NF-kappaB). The involvement of reactive oxygen intermediates (ROI) has been implicated as intracellular messengers in the inducible activation of NF-kappaB. In this study, we compared the efficacy of two antioxidants, alpha-lipoic acid (LA) and N-acetylcysteine (NAC), which are widely recognized NF-kappaB inhibitors. Here, we demonstrate that LA has a more potent activity in inhibiting NF-KappaB-mediated gene expression in THP-1 cells that have been stably transfected with a plasmid bearing a hygromycin B resistance gene under the control of HIV-1 long terminal repeat (LTR) promoter. The spontaneous activation of NF-kappaB in this cell culture system leads to expression of the hygromycin phosphotransferase gene hence rendering the cells resistance to hygromycin B. In this study, the effect of the test compounds against transcriptional activity of HIV-1 LTR was evaluated based on the degree of cellular toxicity due to the inhibitory activity on the expression of hygromycin B resistance gene in the presence of hygromycin B. We also found that 0.2 mM LA could cause 40% reduction in the HIV-1 expression from the TNF-alpha-stimulated OM 10.1, a cell line latently infected with HIV-1. On the other hand, 10 mM NAC was required to elicit the same effect. Furthermore, the initiation of HIV-1 induction by TNF-alpha was completely abolished by 1 mM LA. These findings confirm the involvement of ROI in NF-kappaB-mediated HIV gene expression as well as the efficacy of LA as a therapeutic regimen for HIV infection and acquired immunodeficiency syndrome (AIDS). Moreover, this study validates the applicability of our present assay system which we primarily designed for the screening of candidate drugs against HIV-1 gene expression.

Acetylcysteine↗
PubMed2005

alpha-Lipoic acid supplementation inhibits oxidative damage, accelerating chronic wound healing in patients undergoing hyperbaric oxygen therapy.

Hyperbaric oxygen (HBO) therapy is successfully used for the treatment of a variety of conditions. However, prolonged exposure to high concentrations of oxygen induces production of reactive oxygen species, causing damage to the cells. Thus, antioxidant supplementation has been proposed as an adjuvant to attenuate such deleterious secondary effects. We evaluated the effects of alpha-lipoic acid (LA) in patients affected by chronic wounds undergoing HBO treatment. LA supplementation efficiently reduces both the lipid and DNA oxidation induced by oxygen exposure. LA exerted its antioxidant activity by directly interacting with free radicals or by recycling vitamin E. An inhibitory effect of LA on the pro-inflammatory cytokine interleukin-6 was observed. Taken together, we demonstrated an adjuvant effect of LA in HBO therapy used for impaired wound healing treatment. We propose that LA may be used to further promote the beneficial effects of HBO therapy.

Administration, Oral↗
PubMed1978

Radical scavenging as the mechanism for stimulation of prostaglandin cyclooxygenase and depression of inflammation by lipoic acid and sodium iodide.

Certain radical-trapping reducing agents have been shown to stimulate prostaglandin biosynthesis in vitro (1--6) and to depress phorbol myristate acetate-induced mouse ear edema (16). The increased prostaglandin synthesis resulted from influences on the cyclooxygenase. To ascertain whether these alterations were due to direct interaction with the enzyme or to indirect scavenging of the oxidant released during PGG2 reduction, we report the effects of lipoic acid and sodium iodide. Both of these agents stimulated the enzymatic oxygenation of arachidonic acid, increased the reduction of PGG2 to PGH2, quenched the EPR signal induced by arachidonic acid and depressed mouse ear edema. In addition to discovering two unusual antiinflammatory agents, we have confirmed that materials with entirely different structures can have identical effects on the cyclooxygenase, suggesting indirect stimulation of this enzyme due to trapping of the oxidant.

Animals↗
PubMed2006

Lipoic acid as a novel treatment for Alzheimer's disease and related dementias.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that destroys patient memory and cognition, communication ability with the social environment and the ability to carry out daily activities. Despite extensive research into the pathogenesis of AD, a neuroprotective treatment - particularly for the early stages of disease - remains unavailable for clinical use. In this review, we advance the suggestion that lipoic acid (LA) may fulfil this therapeutic need. A naturally occurring precursor of an essential cofactor for mitochondrial enzymes, including pyruvate dehydrogenase (PDH) and alpha-ketoglutarate dehydrogenase (KGDH), LA has been shown to have a variety of properties which can interfere with pathogenic principles of AD. For example, LA increases acetylcholine (ACh) production by activation of choline acetyltransferase and increases glucose uptake, thus supplying more acetyl-CoA for the production of ACh. LA chelates redox-active transition metals, thus inhibiting the formation of hydroxyl radicals and also scavenges reactive oxygen species (ROS), thereby increasing the levels of reduced glutathione. Via the same mechanisms, downregulation redox-sensitive inflammatory processes is also achieved. Furthermore, LA can scavenge lipid peroxidation products such as hydroxynonenal and acrolein. The reduced form of LA, dihydrolipoic acid (DHLA), is the active compound responsible for most of these beneficial effects. R-alpha-LA can be applied instead of DHLA, as it is reduced by mitochondrial lipoamide dehydrogenase, a part of the PDH complex. In this review, the properties of LA are explored with particular emphasis on how this agent, particularly the R-alpha-enantiomer, may be effective to treat AD and related dementias.

Aged↗
PubMed2003

Effect of single and combined supply of glutamine, glycine, N-acetylcysteine, and R,S-alpha-lipoic acid on glutathione content of myelomonocytic cells.

BACKGROUND & AIMS: Several diseases are characterised by decreased glutathione (GSH) levels due to an enhanced formation of oxygen radicals. To increase GSH levels, the additional supply of GSH precursors was suggested. In this study we evaluated the potency of a single and combined administration of the GSH modulating substances glutamine (GLN), N-acetylcysteine (NAC), and glycine (GLY) as well as R,S-alpha-lipoic acid (LA) to enhance intracellular GSH content in a well-defined model system. RESULTS: Exposure of myelomonocytic U937 cells for 24 h to GLN revealed a 1.5-fold enhancement of GSH levels with a concomitant decrease in the formation of reactive oxygen species and lipid peroxidation. Addition of NAC stimulated GSH formation only at subphysiological GLN levels. GLY enhanced GSH levels under GLN starvation, but caused a diminution of GSH content under optimal GLN supply. LA in combination with 2 mmol/l GLN evoked a 3.6-fold enhancement of GSH content compared to GLN starved cells. CONCLUSION: These results demonstrate that the GSH content of U937 cells is dependent on the supply of GLN, NAC, LA, and GLY. Combinations of the single substances can enhance but also decrease the intracellular GSH content, which is of clinical importance when supplying GSH-modulating substances to patients.

Acetylcysteine↗
PubMed2006

Bioavailability of selenium from the selenotrisulphide derivative of lipoic acid.

BACKGROUND/PURPOSE: Selenium is a required micronutrient in mammals, needed for the activity of enzymes that contain selenocysteine at their active site. Several isoenzymes of glutathione peroxidase and thioredoxin reductase contain selenocysteine and thus the nutritional status of selenium in tissues can have significant impact on the steady state level of reactive oxygen species. The aims of this study were to evaluate the bioavailability of selenium derived from the selenotrisulfide derivative of lipoic acid (LASe) and determine the ability of this compound to be absorbed into skin. METHODS: Bioavailability of selenium derived from LASe was determined using a keratinocyte cell model (HaCat). Efficiency of utilization of selenium was assessed by following the decrease in the incorporation of radiolabeled selenite (75Se) in the presence of increasing concentration of selenium compounds. Percutaneous absorption of LASe was measured by determining selenium levels in full thickness biopsy of skin using a Yorkshire pig model. RESULTS: LASe was efficiently absorbed topically into pig skin, a good model of human skin. In a keratinocyte cell line LASe was an efficient source of selenium for selenoprotein synthesis, demonstrating that LASe is a good candidate as a topical selenium micronutrient. Both L-selenomethionine and selenate were found to be poor sources of selenium for selenoprotein synthesis in the skin cell model and L-selenomethionine was poorly absorbed into pig skin. CONCLUSION: These results indicate that stable selenotrisulfides, such as LASe, are good candidates for testing as topical selenium supplements.

Administration, Cutaneous↗
PubMed2006

Lipoic acid affects cellular migration into the central nervous system and stabilizes blood-brain barrier integrity.

Reactive oxygen species (ROS) play an important role in various events underlying multiple sclerosis (MS) pathology. In the initial phase of lesion formation, ROS are known to mediate the transendothelial migration of monocytes and induce a dysfunction of the blood-brain barrier (BBB). In this study, we describe the beneficial effect of the antioxidant alpha-lipoic acid (LA) on these phenomena. In vivo, LA dose-dependently prevented the development of clinical signs in a rat model for MS, acute experimental allergic encephalomyelitis (EAE). Clinical improvement was coupled to a decrease in leukocyte infiltration into the CNS, in particular monocytes. Monocytes isolated from the circulation of LA-treated rats revealed a reduced migratory capacity to cross a monolayer of rat brain endothelial cells in vitro compared with monocytes isolated from untreated EAE controls. Using live cell imaging techniques, we visualized and quantitatively assessed that ROS are produced within minutes upon the interaction of monocytes with brain endothelium. Monocyte adhesion to an in vitro model of the BBB subsequently induced enhanced permeability, which could be inhibited by LA. Moreover, administration of exogenous ROS to brain endothelial cells induced cytoskeletal rearrangements, which was inhibited by LA. In conclusion, we show that LA has a protective effect on EAE development not only by affecting the migratory capacity of monocytes, but also by stabilization of the BBB, making LA an attractive therapeutic agent for the treatment of MS.

Acute Disease↗
PubMedDate not supplied

[The effect of lipoic acid on the components of the glutathione system in the lacrimal fluid of patients with open-angle glaucoma].

Nonprotein SH groups and gamma-glutamyl transpeptidase were detected in the lacrimal fluid of patients with open-angle glaucoma and senile cataract and in controls (in 82 and 100% of the examinees, respectively). In stage II glaucoma SH group level was found reduced vs. that in stage I or control. Intake of lipoic acid by patients with stage II glaucoma resulted in a reliable increase of lacrimal SH group level. Measurements of lacrimal fluid nonprotein SH groups may be used to monitor antioxidant therapy of patients with open-angle glaucoma.

Adult↗
PubMed2005

The protective role of DL-alpha-lipoic acid in the oxidative vulnerability triggered by Abeta-amyloid vaccination in mice.

Recent reports indicate that beta-amyloid peptide (Abeta) vaccine based therapy for Alzheimer's disease (AD) may be on the horizon. There are however, concerns about the safety of this approach. Immunization with Abeta has several disadvantages, because it crosses the blood brain barrier and cause inflammation and neurotoxicity. The present work is aimed to study the protective effective of alpha-lipoic acid (LA) in the oxidative vulnerability of beta-amyloid in plasma, liver, spleen and brain, when Abeta fibrils are given intraperitoneally in inflammation induced mice. Result shows that reactive oxygen species (ROS) in the astrocytes of inflammation induced mice along with Abeta (IA) has shown 2.5-fold increase when compared with LA treated mice. The increased level of lipid peroxidase (LPO) (p < 0.05) and decreased antioxidant status (p < 0.05) were observed in the plasma, liver, spleen and brain of LA induced mice when compared with LA treated mice. Data shows that there were no significant changes observed between the control and LA treated mice. Our biochemical and histological results highlight that significant oxidative vulnerability was observed in IA treated mice, which was prevented by LA therapy. Our findings suggest that the antioxidant effect of LA when induced with Abeta may serve as a potent therapeutic tool for inflammatory AD models.

Adenosine Triphosphatases↗
PubMed2006

Lipoic acid, a lead structure for multi-target-directed drugs for neurodegeneration.

Nowadays, drug discovery based on a single-target-directed strategy seems inappropriate for the treatment of complex diseases that have multiple pathogenic factors. Recent research into new drugs, which are able to hit different targets, highlights the idea that a single molecule could be sufficient to treat multi-factorial diseases. In this review, examples of multi-target-directed compounds derived from lipoic acid are examined.

Animals↗
PubMed2002

Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid.

We test whether the dysfunction with age of carnitine acetyltransferase (CAT), a key mitochondrial enzyme for fuel utilization, is due to decreased binding affinity for substrate and whether this substrate, fed to old rats, restores CAT activity. The kinetics of CAT were analyzed by using the brains of young and old rats and of old rats supplemented for 7 weeks with the CAT substrate acetyl-l-carnitine (ALCAR) and/or the mitochondrial antioxidant precursor R-alpha-lipoic acid (LA). Old rats, compared with young rats, showed a decrease in CAT activity and in CAT-binding affinity for both substrates, ALCAR and CoA. Feeding ALCAR or ALCAR plus LA to old rats significantly restored CAT-binding affinity for ALCAR and CoA, and CAT activity. To explore the underlying mechanism, lipid peroxidation and total iron and copper levels were assayed; all increased in old rats. Feeding old rats LA or LA plus ALCAR inhibited lipid peroxidation but did not decrease iron and copper levels. Ex vivo oxidation of young-rat brain with Fe(II) caused loss of CAT activity and binding affinity. In vitro oxidation of purified CAT with Fe(II) inactivated the enzyme but did not alter binding affinity. However, in vitro treatment of CAT with the lipid peroxidation products malondialdehyde or 4-hydroxy-nonenal caused a decrease in CAT-binding affinity and activity, thus mimicking age-related change. Preincubation of CAT with ALCAR or CoA prevented malondialdehyde-induced dysfunction. Thus, feeding old rats high levels of key mitochondrial metabolites can ameliorate oxidative damage, enzyme activity, substrate-binding affinity, and mitochondrial dysfunction.

Acetylcarnitine↗
PubMedDate not supplied

Protective effects of early administration of alpha-lipoic acid against lipopolysaccharide-induced plasma lipid peroxidation.

Lipopolysaccharide (LPS), called endotoxin, is a major component of Gram-negative bacteria cell wall. LPS stimulates the synthesis and release of several metabolites from mammalian phagocytes which leads to fulminant systemic inflammation (endotoxic shock). Among LPS-induced metabolites, reactive oxygen species are considered to play crucial role in the pathogenesis of endotoxic shock via oxidative stress generation. In this study, the effect of early administration of antioxidant alpha-lipoic acid (LA) on plasma lipid peroxidation and total antioxidant blood capacity was evaluated in endotoxic shock in rats. Lipid peroxidation was measured as plasma thiobarbituric acid reactive substances (TBARS) levels, while total blood antioxidant capacity was assessed as ferric reducing ability of plasma (FRAP). The endotoxic shock was induced by administration of LPS (Escherichia coli 026:B6, 30 mg/kg, iv) in anesthetized rats. Then, 30 min later, animals were treated intravenously (iv) with LA at 60 mg/kg. After 5 h observation animals were killed and blood from heart was taken for TBARS and FRAP measurements. LPS injected to saline-pretreated animals resulted in development of oxidative stress indicated by significant increases in plasma TBARS and significant decrease in total antioxidant capacity of plasma. Conversely, LA injected to saline pretreated animals caused an increase in FRAP values and the decrease in TBARS levels. The administration of LA 0.5 h after LPS challenge resulted in an increase in FRAP values and decrease in plasma lipid peroxidation as compared to LPS group. Moreover, the levels of TBARS and FRAP in LPS + LA group were similar to those observed in LA group. In conclusion, our present study demonstrates that early treatment with LA significantly protects against endotoxin-induced oxidative stress in rats.

Animals↗
PubMed2001

Alpha-lipoic acid protects rat cortical neurons against cell death induced by amyloid and hydrogen peroxide through the Akt signalling pathway.

Substantial evidence suggests that the accumulation of beta-amyloid (Abeta)-derived peptides contributes to the aetiology of Alzheimer's disease (AD) by stimulating formation of free radicals. Thus, the antioxidant alpha-lipoate, which is able to cross the blood-brain barrier, would seem an ideal substance in the treatment of AD. We have investigated the potential effectiveness of alpha-lipoic acid (LA) against cytotoxicity induced by Abeta peptide (31-35) (30 microM) and hydrogen peroxide (H(2)O(2)) (100 microM) with the cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction and fluorescence dye propidium iodide assays in primary neurons of rat cerebral cortex. We found that treatment with LA protected cortical neurons against cytotoxicity induced by Abeta or H(2)O(2). In addition, LA-induced increase in the level of Akt in the neurons was observed by Western blot. The LA-induced neuroprotection and Akt increase were attenuated by pre-treatment with the phosphatidylinositol 3-kinase inhibitor, LY294002 (50 microM). Our data suggest that the neuroprotective effects of the antioxidant LA are partly mediated through activation of the PKB/Akt signaling pathway.

Alzheimer Disease↗