Effect Of Lipoic Acid Research Articles

Effects of lipoic acid and n-3 long-chain polyunsaturated fatty acid on the liver ovariectomized rat model of menopause.

Bilateral ovariectomy is an experimental model used to analyse the effects of menopause and develop strategies to mitigate the deleterious effects of this condition. Supplementation of the diet with antioxidants has been used to reduce potential oxidative stress caused by menopause. The purpose of the study was to analyse the effects of α-lipoic acid (LA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), dietary supplementation on oxidative stress in the livers of ovariectomized rats. In this study, we evaluated the effect of dietary supplementation with LA, DHA and EPA for a period of 16 weeks on oestrogen levels and oxidative stress biomarkers in the livers of ovariectomized 25 three-month-old rats. Serum oestrogen levels were lower after ovariectomy but were not altered by dietary treatments. LA was capable of acting in the liver, recovering the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase, and reducing protein oxidative damage. Moreover, LA supplementation reduced nitrite and nitrate levels. DHA and EPA recovered the antioxidant activity of cytosolic and mitochondrial superoxide dismutase, decreasing protein oxidation. Protection against lipid oxidation differed between treatments. The DHA-treated group showed increased levels of the lipid peroxidation biomarker malondialdehyde compared to the ovariectomized group. However, malondialdehyde levels were not altered by EPA treatment. The results suggest that the antioxidant response varies among evaluated supplementations and all supplements were able to alter enzymatic and non-enzymatic antioxidants in the livers of ovariectomized rats. DHA presented the most evident antioxidant effect, decreasing protein and lipid damage.

Effects of Lipoic Acid on High-Fat Diet-Induced Alteration of Synaptic Plasticity and Brain Glucose Metabolism: A PET/CT and 13C-NMR Study

High-fat diet (HFD)-induced obesity is accompanied by insulin resistance and compromised brain synaptic plasticity through the impairment of insulin-sensitive pathways regulating neuronal survival, learning, and memory. Lipoic acid is known to modulate the redox status of the cell and has insulin mimetic effects. This study was aimed at determining the effects of dietary administration of lipoic acid on a HFD-induced obesity model in terms of (a) insulin signaling, (b) brain glucose uptake and neuronal- and astrocytic metabolism, and (c) synaptic plasticity. 3-Month old C57BL/6J mice were divided into 4 groups exposed to their respective treatments for 9 weeks: (1) normal diet, (2) normal diet plus lipoic acid, (3) HFD, and (4) HFD plus lipoic acid. HFD resulted in higher body weight, development of insulin resistance, lower brain glucose uptake and glucose transporters, alterations in glycolytic and acetate metabolism in neurons and astrocytes, and ultimately synaptic plasticity loss evident by a decreased long-term potentiation (LTP). Lipoic acid treatment in mice on HFD prevented several HFD-induced metabolic changes and preserved synaptic plasticity. The metabolic and physiological changes in HFD-fed mice, including insulin resistance, brain glucose uptake and metabolism, and synaptic function, could be preserved by the insulin-like effect of lipoic acid.

Effect of Lipoic Acid on the Biochemical Mechanisms of Resistance to Bortezomib in SH-SY5Y Neuroblastoma Cells.

Neuroblastoma (NB) is an extracranial solid cancer and the most common cancer in infancy. Despite the standard treatment for NB is based on the combination of chemotherapeutic drugs such as doxorubicin, vincristine, cyclophosphamide, and cisplatin, chemoresistance occurs over the time. The aim of the present research was to evaluate the effect of bortezomib (BTZ) (50nM) on NB cell viability and how lipoic acid (ALA) (100μM) modifies pharmacological response to this chemotherapeutic agent. Cell viability was assessed by ATP luminescence assay whereas expression of oxidative stress marker (i.e., heme oxygenase-1) and endoplasmic reticulum stress proteins was performed by real-time PCR, western blot, and immunofluorescence. Our data showed that BTZ treatment significantly reduced cell viability when compared to untreated cultures (about 40%). Interestingly, ALA significantly reduced the efficacy of BTZ (about 30%). Furthermore, BTZ significantly induced heme oxygenase-1 as a result of increased oxidative stress and such overexpression was prevented by concomitant treatment with ALA. Similarly, ALA significantly reduced BTZ-mediated endoplasmic reticulum stress as measured by reduction in BiP1 and IRE1α, ERO1α, and PDI expression. In conclusion, our data suggest that BTZ efficacy is dependent on cellular redox status and such mechanisms may be responsible of chemoresistance to this chemotherapeutic agent.

MP12-12 ?-LIPOIC ACID SUPPRESSES CYSTINE STONE FORMATION IN A GENETIC MOUSE MODEL OF CYSTINURIA

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology I1 Apr 2017MP12-12 ?-LIPOIC ACID SUPPRESSES CYSTINE STONE FORMATION IN A GENETIC MOUSE MODEL OF CYSTINURIA Tiffany Zee, Neelanjan Bose, Jarcy Zee, Jennifer Beck, See Yang, Jaspreet Parihar, Min Yang, Sruthi Damodar, David Hall, Monique O'Leary, Arvind Ramanathan, Roy Gerona, David Killilea, Thomas Chi, Jay Tischfield, Amrik Sahota, Arnold Kahn, Pankaj Kapahi, and Marshall Stoller Tiffany ZeeTiffany Zee More articles by this author , Neelanjan BoseNeelanjan Bose More articles by this author , Jarcy ZeeJarcy Zee More articles by this author , Jennifer BeckJennifer Beck More articles by this author , See YangSee Yang More articles by this author , Jaspreet PariharJaspreet Parihar More articles by this author , Min YangMin Yang More articles by this author , Sruthi DamodarSruthi Damodar More articles by this author , David HallDavid Hall More articles by this author , Monique O'LearyMonique O'Leary More articles by this author , Arvind RamanathanArvind Ramanathan More articles by this author , Roy GeronaRoy Gerona More articles by this author , David KillileaDavid Killilea More articles by this author , Thomas ChiThomas Chi More articles by this author , Jay TischfieldJay Tischfield More articles by this author , Amrik SahotaAmrik Sahota More articles by this author , Arnold KahnArnold Kahn More articles by this author , Pankaj KapahiPankaj Kapahi More articles by this author , and Marshall StollerMarshall Stoller More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.434AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Cystinuria is a disorder characterized chronic kidney stone formation and caused by genetic mutations in the heterodimeric cystine transporter (SLC3A1 and SLC7A9) that is responsible for cystine reabsorption. Individuals afflicted with cystinuria are often treated by hyper-hydration, urine alkalization, and/or pharmacological interventions aimed at increasing cystine solubility in urine. However, these treatments are limited in their effectiveness and often have serious adverse side effects. The objective of this study is to use a mouse model of cystinuria to identify novel approaches towards the treatment of cystinuria. METHODS Methods: Using longitudinal micro-computed tomography, Slc3a1-/- mouse cystine bladder stone formation was calculated at growth rate of approximately 1 mm3/day. This measure was used to evaluate interventions aimed at attenuating stone growth. A linear mixed model with random intercept was used to assess stone growth rates between treated versus control mice. RESULTS Lipoic acid was found to be a potent inhibitor of cystine stone formation in a Slc3a1-/- mouse model of cystinuria. Treatment with lipoic acid attenuated existing cystine stone growth, and prevented stone formation in young Slc3a1-/- mice. The inhibitory effect was found to be dose-dependent, and independent of lipoic acid effects on the antioxidant response pathway. Ex vivo cystine precipitation analysis revealed that lipoic acid treatment increased cystine solubility in urine. CONCLUSIONS Treatment with the nutritional supplement lipoic acid protects against stone formation in a mouse model of cystinuria. This result identifies a novel application of lipoic acid that increases urinary cystine solubility independently of pH, and may highlight a new avenue for understanding treatment strategies for cystinuric patients. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e149 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Tiffany Zee More articles by this author Neelanjan Bose More articles by this author Jarcy Zee More articles by this author Jennifer Beck More articles by this author See Yang More articles by this author Jaspreet Parihar More articles by this author Min Yang More articles by this author Sruthi Damodar More articles by this author David Hall More articles by this author Monique O'Leary More articles by this author Arvind Ramanathan More articles by this author Roy Gerona More articles by this author David Killilea More articles by this author Thomas Chi More articles by this author Jay Tischfield More articles by this author Amrik Sahota More articles by this author Arnold Kahn More articles by this author Pankaj Kapahi More articles by this author Marshall Stoller More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The effects of lipoic acid on redox status in brain regions and systemic circulation in streptozotocin-induced sporadic Alzheimer’s disease model

While the deterioration of insulin-glucose metabolism (IGM), impaired redox homeostasis (IRH), β-amyloid accumulation was reported in Sporadic Alzheimer's Disease (SAD) model, aforementioned factors related to lipoic acid administration and anthropometric indexes (AIs) are not yet studied with integrative approach. β-amyloid accumulation, redox homeostasis biomarkers and AIs are investigated in SAD model. Streptozotocin-induced inhibition of insulin-signaling cascade but not GLUT-2 and GLUT-3 transporters takes a role in β-amyloid accumulation. Inhibition types are related to IRH in cortex, hippocampus and systemic circulation. Lipoic acid (LA) shows both antioxidant and prooxidant effect according to the anatomical location. LA administration also leads to improved AIs during GLUT-2 inhibition and cortical redox status in GLUT-3 inhibited group. Optimal LA action could be possible if its redox behavior is balanced to antioxidant effect. Diagnostic usage of systemic IRH parameters as biomarkers and their possible correlations with deteriorated IGM should be investigated. Graphical abstract ᅟ.

Molecular hepatoprotective effects of lipoic acid against carbon tetrachloride-induced liver fibrosis in rats: Hepatoprotection at molecular level.

Liver fibrosis is a noteworthy well-being issue that can prompt the progression of liver cirrhosis and hepatocellular carcinoma. Prominently, many antioxidants have been shown to have defensive impacts against liver fibrosis. Subsequently, in the present study, the viability of alpha-lipoic acid (α-LA) in ensuring against carbon tetrachloride (CCl4)-actuated liver fibrosis and the mechanism(s) involved in this defensive impact were considered in rats. The present results uncovered that in the CCl4-treated group, the expression of antioxidant enzymes and matrix metalloproteinase-13 (MMP-13) messenger RNA (mRNA) was downregulated ( p < 0.05), and the levels of lipid peroxide and nitric oxide were increased ( p < 0.05) in the treated rat livers along with increased collagen deposition compared to that of the control group. Also, the gene expression levels of the proinflammatory factors interleukin-6 and tumor necrosis factor-alpha, nuclear factor-kappa B (NF-κB) p65, transforming growth factor-alpha, and inducible nitric oxide synthase (iNOS) were upregulated significantly ( p < 0.05) in the CCl4 group. These negative impacts were all restrained by α-LA. These outcomes show that α-LA might be compelling at forestalling collagen deposition and hepatic oxidative stress as well as downregulating the expression of hepatic proinflammatory cytokines, iNOS, and NF-κB and upregulating MMP-13 expression.

Effect of lipoic acid on paraoxonase-1 and paraoxonase-3 protein levels, mRNA expression and arylesterase activity in liver hepatoma cells.

Paraoxonase-1 (PON1) and PON3 (PON3) are anti-atherosclerotic enzymes, synthesized primarily in liver and bound to HDL in circulation. The aim of the present study was to investigate the effects of therapeutic doses of lipoic acid on PON1 and PON3 protein levels, mRNA expression and arylesterase activity in liver. We treated HepG2 cells with 10, 40 and 200 μM lipoic acid for 72 h. Cell viability was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. PON1 and PON3 protein levels were measured by Western blotting, their mRNA expression was measured by quantitative PCR and arylesterase activity was measured spectrophotometrically. 200 µM lipoic acid caused a significant increase on PON1 and PON3 protein levels and arylesterase activity as compared with control, 10 µM and 40 µM lipoic acid-treated cells. 200 µM lipoic acid also caused a significant decrease on PON1 mRNA expression whereas on a significant increase PON3 mRNA expression as compared with control, 10 µM and 40 µM lipoic acid-treated cells. Our study showed that although lipoic acid up-regulates PON3 but down-regulates PON1 mRNA expression, it increases both PON1 and PON3 protein levels and arylesterase activity in HepG2 cells. We can report that lipoic acid may be useful for preventing atherosclerosis at therapeutic doses.

Protective effects of lipoic acid against acrylamide-induced neurotoxicity: involvement of mitochondrial energy metabolism and autophagy.

Acrylamide (ACR) is a chronic neurotoxin that is generated in high-starch foods during heat processing. Alpha-lipoic acid (LA) is an antioxidant that occurs in most plants and animals. The objective of this study was to reveal the mechanism of ACR-triggered neurotoxicity and identify the protective role of LA in SH-SY5Y cells. In this study, LA restored ACR-stimulated depletion of glutathione content and mitochondrial membrane potential, moderated the activation of inflammatory pathways, and recovered the Keap1/Nrf2 pathway. Moreover, LA upregulated the activities of oxidative phosphorylation complexes and diminished ACR-induced variation in AMPK/GSK3β, Ca2+ disturbance, and ATP depletion. The Sirt1/PGC-1α pathway was inhibited by ACR. Notably, autophagy was activated in the mitochondria-mediated apoptosis induced by ACR, which was also blocked by LA. Overall, our study demonstrated the pivotal roles of the mitochondrial energy metabolism and autophagy in the protective effects of LA and cytotoxicity of ACR in SH-SY5Y cells.

POTENTIAL ADMINISTRATION OF LIPOIC ACID AND COENZYME Q AGAINST ADIPOGENSIS: TARGET FOR WEIGHT REDUCTION.

Background:Body overweight and obesity were considered as a risk factor for many systemic diseases as diabetic hypertension, cardiovascular diseases, and some cancers. The lipoic acid and Co Q are considered as coenzymes needed for enhancement metabolic rate. The goal of this study is to evaluate the anti-obese effect of lipoic acid alone or combined with Co-Q in rats.Materials and Methods:Ninety male albino rats (100-150g) were used in this study, divided into six groups (15 each). Group I: Normal rats fed normal diet. Group II: Rats fed high fat diet (HFD). Group III: Rats fed HFD were given lipoic acid (10 μg/kg b w/day) intra-gastric by stomach tube. Group IV: Rats fed HFD were given Co-Q (10 μg/kg b.w/day) intra-gastric. Group V: Rats fed HFD were given lipoic acid (50 mg/kg b w/day) and Co-Q (10 μg/kg b. w/day). Group VI: Rats were given orlistat intra-gastric (10 mg/kg b w/day) as positive control for 6 weeks. Serum was subjected for determination of lipid profile, liver function tests atherogenic factor and lipoprotein lipase.Results:It was found that treatment with lipoic acid or Co-Q or combined showed increase in the activity of lipoprotein lipase (P < 0.001) and reduction of atherogenic effect and obesity index (P <0.001). The effect of combined gives good results than orlistat or individual treatment.Conclusion:lipoic acid combined with Co-Q increase fat oxidation and prevent fat accumulation. The consumption of lipoic acid daily promotes fat oxidation and prevents its accumulation in visceral tissues. Further studies should be carried out to examine the mechanistic signals of these nutrients that helps in weight management.

Comparison of the effects of lipoic acid and glutathione against cisplatin-induced ototoxicity in auditory cells

ObjectivesThe aims of this study were to examine lipoic acid (LA)- or glutathione (GSH)-mediated protection against cytotoxicity following cisplatin exposure in HEI-OC1 auditory cells and measure the potential of LA and GSH to scavenge reactive oxygen species (ROS). This study also compares their protective effects and discusses the determination of a preventive or therapeutic dose. MethodsHEI-OC1 cells were pretreated with LA or GSH for 24 h and then exposed to 15 μM cisplatin for 48 h. The resulting cytotoxicity was measured using a cell counting kit-8, and intracellular ROS level was measured using flow cytometry. The protective or anti-ROS effects of LA and GSH were compared. Measurement of caspase 3, 8, 9 activity and Western blot analysis of PARP were performed. ResultsPretreatment with LA at 300 μM and GSH at 3 mM protected HEI-OC1 cells against cisplatin-induced cytotoxicity and significantly reduced the cisplatin-induced increase in ROS. LA showed a significantly more effective protection against cisplatin-induced ototoxicity compared to that shown by GSH (85.4% vs. 73.1% cell viability). Both LA and GSH showed the maximal protective effect at different concentrations in normal or cisplatin-induced cytotoxic conditions. The preventive or therapeutic dose for harmful conditions is quite different for the two drugs and needs careful adjustments. ConclusionThis comparative study on the protective effects of LA and GSH against cisplatin-induced ototoxicity in an auditory cell line posed many challenges. Although LA and GSH showed a significant protective effect against cisplatin, the LA's effect was superior. The concentration at which the maximal protective effect of LA or GSH was noted was 3 times higher in cytotoxic conditions than in normal conditions, which suggests the need for drug dose adjustments based on the purpose (preventive or therapeutic).

Effect of lipoic acid on the activity of caspases and the characteristics of the immune and antioxidant statuses in rats with rheumatoid arthritis

The activity of caspase-3, caspase-8, superoxide dismutase, and catalase and the content of circulating immune complexes and immunoglobulins A, M, and G in the blood serum and muscles of rats in the norm, in experimental rheumatoid arthritis, and by the action of lipoic acid against the background of progressive pathology have been studied. The induction of rheumatoid arthritis in rats was accompanied by an increase in marker parameters and immune status indices, as well as in the activity of caspase-3, caspase-8, superoxide dismutase, and catalase, which was probably caused by excessive generation of reactive oxygen species during the development of pathology. The administration of lipoic acid to rats with rheumatoid arthritis led to a normalization of the parameters, which was evidently due to the capacity of the compound to produce the antioxidant effect and reduce the severity of autoimmune diseases.

Effects of lipoic acid on growth and biochemical responses of common carp fed with carbohydrate diets

Lipoic acid (LA) is an antioxidant that also favors glucose uptake in mammals. Until now, there are no studies evaluating the potential effect of this molecule on glycemic control in fish. It was evaluated LA effects on glucose uptake in common carp Cyprinus carpio fed with carbohydrate diets from two carbohydrate sources: glucose (GLU) and starch (STA), and supplemented or not with LA, being the diets: +GLU/-LA (GLU); +GLU/+LA (GLU+LA); +STA/-LA (STA); and +STA/+LA (STA+LA). Carp juveniles (6.5±0.1g) were fed with each diet ad libitum 4 times a day, during 68days. Muscle glycogen concentration was higher (p<0.05) in GLU and GLU+LA than in STA and STA+LA groups. On fish fed with starch, muscle cholesterol and triglyceride concentrations were higher (p<0.05) in fish fed diets supplemented with LA. Muscle protein levels were higher in fish fed with LA, independent of the diet carbohydrate source. Lipid peroxidation was significantly reduced (p<0.05) in fish muscle on fish fed the STA+LA diets when compared with the STA diet. Our findings indicate that LA modulates lipid, proteins and carbohydrate metabolism together with the well-known antioxidant effect. Also, LA showed to enhance starch utilization taking into account muscle cholesterol and triglyceride levels.

Do antioxidant supplements benefit patients with multiple sclerosis?

Do antioxidant supplements benefit patients with multiple sclerosis?

Protein Disulfide Levels and Lens Elasticity Modulation: Applications for Presbyopia.

PurposeThe purpose of the experiments described here was to determine the effects of lipoic acid (LA)-dependent disulfide reduction on mouse lens elasticity, to synthesize the choline ester of LA (LACE), and to characterize the effects of topical ocular doses of LACE on mouse lens elasticity.MethodsEight-month-old mouse lenses (C57BL/6J) were incubated for 12 hours in medium supplemented with selected levels (0–500 μM) of LA. Lens elasticity was measured using the coverslip method. After the elasticity measurements, P-SH and PSSP levels were determined in homogenates by differential alkylation before and after alkylation. Choline ester of LA was synthesized and characterized by mass spectrometry and HPLC. Eight-month-old C57BL/6J mice were treated with 2.5 μL of a formulation of 5% LACE three times per day at 8-hour intervals in the right eye (OD) for 5 weeks. After the final treatment, lenses were removed and placed in a cuvette containing buffer. Elasticity was determined with a computer-controlled instrument that provided Z-stage upward movements in 1-μm increments with concomitant force measurements with a Harvard Apparatus F10 isometric force transducer. The elasticity of lenses from 8-week-old C57BL/6J mice was determined for comparison.ResultsLipoic acid treatment led to a concentration-dependent decrease in lens protein disulfides concurrent with an increase in lens elasticity. The structure and purity of newly synthesized LACE was confirmed. Aqueous humor concentrations of LA were higher in eyes of mice following topical ocular treatment with LACE than in mice following topical ocular treatment with LA. The lenses of the treated eyes of the old mice were more elastic than the lenses of untreated eyes (i.e., the relative force required for similar Z displacements was higher in the lenses of untreated eyes). In most instances, the lenses of the treated eyes were even more elastic than the lenses of the 8-week-old mice.ConclusionsAs the elasticity of the human lens decreases with age, humans lose the ability to accommodate. The results, briefly described in this abstract, suggest a topical ocular treatment to increase lens elasticity through reduction of disulfides to restore accommodative amplitude.

Lipoic Acid Exerts Antioxidant and Anti-inflammatory Effects in Response to Heat Shock in C2C12 Myotubes.

This study explored that lipoic acid treatment for 24h significantly upregulated and promoted heat shock-induced catalase expression and downregulated GPx1 messenger RNA (mRNA) expression, indicating that lipoic acid exhibits antioxidant activity in the decomposition of hydrogen peroxide by upregulating catalase expression. Moreover, lipoic acid treatment for 3h increased and promoted heat shock-induced interleukin (IL)-6 mRNA and protein levels and that for 24h downregulated IL-6 mRNA expression, suggesting a dual effect of lipoic acid on IL-6 regulation. Lipoic acid alone failed to increase or reduce tumor necrosis factor (TNF)-α mRNA and protein levels, whereas heat shock alone downregulated TNF-α mRNA and protein expression. These data suggest that lipoic acid does not have a proinflammatory role and that heat shock acts as an anti-inflammatory agent by downregulating TNF-α expression in C2C12 myotubes. Moreover, lipoic acid or heat shock alone upregulated the IL-6 receptor (IL-6R-α) and glycoprotein 130 (gp130) mRNA expression followed by IL-6 expression; these data indicate that the regulation of lipoic acid or heat shock is mediated by IL-6R signaling, thus suggesting that C2C12 myotubes possesses a mechanism for regulating IL-6R and gp130 expression following lipoic acid treatment or heat shock.

Cardioprotective effects of lipoic acid, quercetin and resveratrol on oxidative stress related to thyroid hormone alterations in long-term obesity

This study investigated possible mechanisms for cardioprotective effects of lipoic acid (LA), quercetin (Q) and resveratrol (R) on oxidative stress related to thyroid hormone alterations in long-term obesity. Female C57BL/6 mice were fed on high-fat diet (HFD), HFD+LA, HFD+R, HFD+Q and normal diet for 26weeks. Body weight, blood pressure, thyroid hormones, oxidative stress markers, angiotensin converting enzyme (ACE), nitric oxide synthase (NOS) and ion pump activities were measured, and expression of cardiac genes was analyzed by real-time polymerase chain reaction. HFD induced marked increase (P<.05) in body weight, blood pressure and oxidative stress, while plasma triidothyronine levels reduced. ACE activity increased (P<.05) in HFD mice (0.69±0.225U/mg protein) compared with controls (0.28±0.114U/mg protein), HFD+LA (0.231±0.02U/mg protein) and HFD+Q (0.182±0.096U/mg protein) at 26weeks. Moreover, Na+/K+-ATPase and Ca2+-ATPase activities increased in HFD mice whereas NOS reduced. A 1.5-fold increase in TRα1 and reduction in expression of the deiodinase iodothyronine DIO1, threonine protein kinase and NOS3 as well as up-regulation of AT1α, ACE, ATP1B1, GSK3β and Cja1 genes also occurred in HFD mice. Conversely, LA, Q and R inhibited weight gain; reduced TRα1 expression as well as increased DIO1; reduced ACE activity and AT1α, ATP1B1 and Cja1 gene expression as well as inhibited GSK3β; increased total antioxidant capacity, GSH and catalase activity; and reduced blood pressure. In conclusion, LA, resveratrol and quercetin supplementation reduces obesity thereby restoring plasma thyroid hormone levels and attenuating oxidative stress in the heart and thus may have therapeutic potential in heart diseases.

Effect of Lipoic Acid on Serum Paraoxonase-1 and Paraoxonase-3 Protein Levels and Activities in Diabetic Rats.

The aim of the present study was to investigate the effect of streptozotocin-induced diabetes mellitus and lipoic acid treatment on serum paraoxonase-1 and paraoxonase-3 protein levels and paraoxonase, arylesterase and lactonase activities.36 rats were equally and randomly divided into 4 groups as control, lipoic acid, diabetes and diabetes+lipoic acid. To induce diabetes, a single dose of streptozotocin (40 mg/kg) was injected intraperitoneally to diabetes and diabetes+lipoic acid groups. Lipoic acid (10 mg/kg/day) was injected intraperitoneally for 14 days to lipoic acid and diabetes+lipoic acid groups. Serum PON1 and PON3 protein levels were measured by western blotting. Serum paraoxonase, arylesterase and lactonase activities were determined by the measuring initial rate of substrate (paraoxon, phenylacetate and dihydrocoumarin) hydrolysis.Streptozotocin-induced diabetes mellitus caused a significant decrease whereas lipoic acid treatment caused a significant increase in serum PON1 and PON3 protein levels and paraoxonase, arylesterase and lactonase activities. The increase percent of serum PON3 protein was higher than that of serum PON1 protein and the increase percent of serum lactonase activity was higher than that of serum paraoxonase and arylesterase activities in diabetes+lipoic acid group.We can report that, like PON1 protein, PON3 protein and actually its lactonase activity may also have a role as an antioxidant in diabetes mellitus and lipoic acid treatment may be useful for the prevention of the atherosclerotic complications of diabetes by increasing serum PON1 and PON3 protein levels and serum enzyme activities.

Effects of Lipoic Acid Supplementation on Activities of Cyclooxygenases and Levels of Prostaglandins E2 and F2α Metabolites, in the Offspring of Rats with Streptozotocin-Induced Diabetes.

Background. Our aim was to evaluate the protective effect of lipoic acid (LA) on fetal outcome of diabetic mothers. Methods. Diabetes was induced in female rats using streptozotocin and rats were made pregnant. Pregnant control (group 1; n = 9; and group 2; n = 7) or pregnant diabetic (group 3; n = 10; and group 4; n = 8) rats were treated daily with either LA (groups 2 and 4) or vehicle (groups 1 and 3) between gestational days 0 and 15. On day 15 of gestation, the fetuses, placentas, and membranes were dissected, examined morphologically, and then homogenized, to measure cyclooxygenase (COX) activities and metabolisms of prostaglandin (PG) E2 (PGEM) and PGF2 α (PGFM) levels. The level of total glutathione was measured in the maternal liver and plasma and in all fetuses. Results. Supplementation of diabetic rats with LA was found to significantly (p < 0.05) reduce resorption rates in diabetic rats and led to a significant (p < 0.05) increase in liver, plasma, and fetuses total glutathione from LA-TD rats as compared to those from V-TD. Decreased levels of PGEM and elevated levels of PGFM in the fetuses, placentas, and membranes were characteristic of experimental diabetic gestation associated with malformation. The levels of PGEM in malformed fetuses from LA-TD mothers was significantly (p < 0.05) higher than those in malformed fetuses from V-TD rats. Conclusions. LA treatment did not completely prevent the occurrence of malformations. Thus, other factors may be involved in the pathogenesis of the diabetes-induced congenital malformations.

Co-administration effects of α-lipoic acid and nucleo CMP on arousal and sensory cortical activity

Objective: To evaluate the combined effects of lipoic acid and nuclear CMP on arousal and sensory cortical activity in normal healthy volunteers. Method: Eighty healthy volunteers enrolled in this study, the volunteers were divided into four groups’. Group A: take a placebo and regarded as controlling. Group B: take nucleo CMP capsule 5mg/day. Group C: take lipoic acid 400 mg/day. Group D: take nucleo CMP and lipoic acid/ day. The duration of treatment was two weeks. CFFF tests measured via Leeds psychomotor battery tester. Student t-test, simple correlation and ANOVA test via SPSS version 18, taking p Results: lipoic acid improves fusion frequency (ascending) insignificantly and flicker (descending) frequency significantly in normal healthy volunteers. Nucleo CMP leads to a significant amelioration of critical flicker frequency, flicker percent and fusion percent p 0.05. Combined lipoic acid and Nucleo CMP produced significant effects on critical flicker frequency, critical fusion frequency, flicker percent and fusion percent p 0.05. Conclusion: lipoic acid and nucleo CMP produced significant arousal effects on normal healthy volunteers and improve cognitive functions. Key words: CFFF, Lipoic acid, Nucleo CMP, Sensory cortical activity.

Evidence for protective effect of lipoic acid and desvenlafaxine on oxidative stress in a model depression in mice.

Oxidative stress is implicated in the neurobiology of depression. Here we investigated oxidative alterations in brain areas of animals submitted to the model of depression induced by corticosterone (CORT) and the effects of the antioxidant compound alpha-lipoic acid (ALA) alone or associated with the antidepressant desvenlafaxine (DVS) in these alterations. Female mice received vehicle or CORT (20 mg/kg) during 14 days. From the 15th to 21st days different animals received further administrations of: vehicle, DVS (10 or 20 mg/kg), ALA (100 or 200 mg/kg), or the combinations of DVS10+ALA100, DVS20+ALA100, DVS10+ALA200, or DVS20+ALA200. Twenty-four hours after the last drug administration prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) were dissected for the determination of the activity of superoxide dismutase (SOD), reduced glutathione (GSH) and lipid peroxidation (LP) levels. CORT significantly increased SOD activity in the PFC and HC, decreased GSH levels in the HC and increased LP in all brain areas studied when compared to saline-treated animals. Decrements of SOD activity were observed in all groups and brain areas studied when compared to controls and CORT. The hippocampal decrease in GSH was reversed by ALA100, DVS10+ALA100, DVS20+ALA100 and DVS20+ALA200. The same DVS+ALA combination groups presented increased levels of GSH in the PFC and ST. The greater GSH levels were observed in the PFC, HC and ST of DVS20+ALA200 mice. LP was reversed in the groups ALA200 (PFC), DVS10+ALA100, DVS20+ALA100 (PFC, HC and ST), and DVS20+ALA200 (PFC, HC). Our findings contribute to the previous preclinical evidences implicating ALA as a promising agent for augmentation therapy in depression.