Effects Of Α-lipoic Acid Research Articles

Effects of α-lipoic acid on growth performance, antioxidant capacity, and immune function in sheep.

α-Lipoic acid (α-LA) was usually applied to improve the ability of removing the reactive oxygen species of host. The affection of α-LA on ruminants was mainly focused on the variation of serum antioxidant and immune indexes, but the research on tissues or organs remained limited. The aim of this study was to explore the effects of dietary supplementation with different levels of α-LA on growth performance, antioxidant status, and immune indexes of serum and tissues in sheep. One hundred Duhu F1 hybrid (Dupo♀ × Hu sheep♂) sheep aged 2 to 3 mo with similar body weight (27.49 ± 2.10 kg) were randomly allocated into five groups. Five diets supplemented with 0 (CTL), 300 (LA300), 450 (LA450), 600 (LA600), and 750 (LA750) mg/kg α-LA were fed to sheep for 60 d. The results showed that α-LA supplementation significantly increased the average daily feed intake (P < 0.05); however, no significant variation was found in the average daily gain, feed conversion rate, carcass weight, and slaughter rate among groups (P > 0.05). Compared with CTL group, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities in serum of LA600 and LA750 groups were increased (P < 0.05). At LA450-LA750 groups, SOD, CAT activities in liver and ileum tissues and GSH-Px activities in ileum tissues were increased than CTL group (P < 0.05), while malondialdehyde (MDA) contents in serum and muscle tissue were decreased than CTL group (P < 0.05). The total antioxidant capacity contents in liver, muscle, and ileum tissues of LA600 group were increased compared with CTL group (P < 0.05). Additionally, the interleukin-10 (IL-10) contents of serum in LA450-LA750 groups were increased than CTL group (P < 0.05); the contents of interleukin-1β (IL-1β) in serum, interleukin-2 (IL-2) in liver, and interleukin-6, IL-1β in muscle were decreased than CTL group (P < 0.05). The content of immunoglobulin A in serum of LA600 group, ileum, and muscle of LA750 group was increased than CTL group (P < 0.05). Based on the quadratic regression analysis of GSH-Px, MDA, IL-2, IL-10, and IL-1β, the optimal dietary α-LA levels were estimated to be 495.75, 571.43, 679.03, 749.75, and 678.25 mg/kg, respectively. This research will provide certain contribution for the effective utilization of α-LA in sheep production.

The Effect of α-lipoic Acid on C-Reactive Protein Level: A Meta-analysis of Randomized, Double-Blind, and Placebo-Controlled Studies.

The C-reactive protein is generally considered a marker of inflammation, and it is widely used in clinical practice as a minimally invasive index of any ongoing inflammatory response. Alpha-lipoic acid (ALA) supplementation can be beneficial for human health, especially in the sense of its anti-inflammatory action. The aim of this meta-analysis was to, based on the currently available highest level of evidence (prospective, randomized, double-blind, and placebo-controlled data), investigate the effect of ALA supplementation on CRP levels. Prospective, randomized, double-blind, and placebo-controlled clinical trials were extracted after a systematic search of PubMed, the Cochrane Library, the Web of Science, EMBASE, and the Scopus databases. A random effect model was used in this meta-analysis to investigate the influence of ALA on the blood CRP level. The subgroup analysis and meta-regression were used to identify the source of heterogeneity. This meta-analysis provided evidence of the positive effect of ALA on the reduction of the blood CRP level. The subgroup analysis and meta-regression results indicated that ALA can reduce the CRP level when administrated at a 600 mg dose, and not in higher or lower doses. Also, a shorter duration of study positively correlates with the reduction of CRP after ALA supplementation.

The Effect of α-Lipoic Acid on Oxidative Stress in Adipose Tissue of Rats with Obesity-Induced Insulin Resistance

Correlation between type 2 diabetes and other abnormalities such as obesity with redox balance disturbance was analyzed in many reports. Nonetheless, antioxidants impact on parameters accompanying these conditions is still unknown. Currently the role of redox imbalance in the adipose tissue has gained a lot of attention. We investigated the impact of α-lipoic acid (ALA) on plasma glucose and insulin concentrations, oxidative stress and inflammation parameters in the subcutaneous (SAT) and visceral (VAT) adipose tissue of high fat diet-fed (HFD) rats. Male Wistar rats were randomly divided into three groups (n = 6) - control diet (CTRL), HFD and HFD with α-lipoic acid (HFD+ALA). HFD increased body weight, plasma insulin and glucose as well as leads to oxidative stress parameters in the adipose tissue. ALA supplementation reduced body weight and oxidative stress parameters more effectively in the visceral than subcutaneous adipose tissue of insulin resistant rats. Insulin resistance led to increased enzymatic and non-enzymatic antioxidant systems, protein and lipid glycoxidation, nitrosative stress, and selected inflammatory parameters more in VAT than in SAT of insulin resistant rats. Moreover, ALA inhibited HFD consequences mainly in VAT mostly through glutathione (GSH) biosynthesis.

Effects of α-Lipoic Acid on Phagocytosis of Oligomeric Beta-Amyloid1-42 in BV-2 Mouse Microglial Cells.

Background and objectives: This study aimed to investigate the enhancing effect of vitamin-like alpha-lipoic acid (ALA) on phagocytosis of oligomeric beta-amyloid (oAβ)1–42 in BV-2 mouse microglial cells.Methods: An in vitro model was established to investigate phagocytosis of oAβ1–42 in BV-2 cells. Transmission electron microscopy images indicated that the morphology of prepared oAβ1–42 was spherical particles. BV-2 cells treated with ALA were incubated with 5(6)-carboxyfluorescein-labeled oAβ1–42 (FAM-oAβ1–42) for 24 h, followed by flow cytometer analysis, western blotting, real-time quantitative PCR, and immunocytochemistry (ICC) analysis to assess the in vitro phagocytosis ability of oAβ1–42.Results: Alpha-lipoic acid significantly increased messenger RNA (mRNA) expression of the CD36 receptor in BV-2 cells. ICC analysis showed that ALA significantly elevated CD36 protein expression in BV-2 cells both with and without oAβ1–42 treatment. Results from the flow cytometry analysis indicated that the CD36 receptor inhibitor significantly attenuated ALA-promoted phagocytosis of FAM-oAβ1–42 in BV-2 cells. Moreover, ICC analysis revealed that ALA caused the translocation of peroxisome proliferator-activated receptor-γ (PPAR-γ), which is known to regulate the expression of CD36 mRNA in BV-2 cells. ALA also elevated both the mRNA and protein expression of cyclooxygenase-2 (COX-2), which is a key enzyme involved in the synthesis of 15-deoxy-Δ12,14-prostaglandin J2 in BV-2 cells.Conclusion: We postulated that ALA enhances oAβ1–42 phagocytosis by upregulating the COX-2/15-deoxy-Δ12,14-prostaglandin J2/PPAR-γ/CD36 pathway in BV-2 cells. Finally, future studies should be conducted with an in vivo study to confirm the findings.

Alpha-Lipoic Acid Prevents Side Effects of Therapeutic Nanosilver without Compromising Cytotoxicity in Experimental Pancreatic Cancer.

Simple SummaryPancreatic ductal adenocarcinoma is among the most aggressive malignancies and improved treatment options are urgently needed. Silver nanoparticles are suggested as potent antitumor agents, but the side effects of silver overdoses may limit the application. The natural anti-oxidant α-lipoic acid might prevent these side effects. We synthesized nanosilver and used it to treat several pancreatic cancer cells and normal cells in the presence or absence of α-lipoic acid. Silver selectively eliminated pancreatic cancer cells and α-lipoic acid supported the cytotoxicity, whereas benign cells largely resisted. α-Lipoic acid formed complexes with silver particles and reduced silver-induced formation of reactive oxygen species, mitochondrial damage and liver toxicity. Our data suggest that nanosilver application in the presence of α-lipoic acid is safe and effective in the treatment of pancreatic cancer.Silver nanoparticles (AgNPs) have attracted attention in cancer therapy and might support the treatment of pancreatic ductal adenocarcinoma (PDAC). Silver is in clinical use in wound dressings, catheters, stents and implants. However, the side effects of systemic AgNP treatment due to silver accumulation limit its therapeutic application. We evaluated whether the antioxidant and natural agent α-lipoic acid might prevent these side effects. We synthesized AgNPs using an Ionic-Pulser® Pro silver generator and determined the concentration by inductively coupled plasma–optical emission spectrometry. The effect of α-lipoic acid was examined in four PDAC and two nonmalignant cell lines by MTT, FACS analysis, TEM, xenotransplantation and immunohistochemistry. The viability of PDAC cells was nearly totally abolished by AgNP treatment, whereas nonmalignant cells largely resisted. α-Lipoic acid prevented AgNP-induced cytotoxicity in nonmalignant cells but not in PDAC cells, which might be due to the higher sensitivity of malignant cells to silver-induced cytotoxicity. α-Lipoic acid protected mitochondria from AgNP-induced damage and led to precipitation of AgNPs. AgNPs reduced the growth of tumor xenografts, and cotreatment with α-lipoic acid protected chick embryos from AgNP-induced liver damage. Together, α-lipoic acid strongly reduced AgNP-induced side effects without weakening the therapeutic efficacy.

α-Lipoic acid treatment alleviates postharvest pericarp browning of litchi fruit by regulating antioxidant ability and energy metabolism

Litchi fruit has high commercial value and significant benefits for humans. However, pericarp browning, as the indicator of litchi fruit senescence, limits the shelf life of litchi fruit. Effect of α-lipoic acid (α-LA) that has great antioxidant potential, on litchi fruit senescence was investigated. Results showed that α-LA delayed pericarp browning and attenuated redox stress of litchi fruit, indicated by lower hydrogen peroxide (H2O2) and superoxide radical (O2−·) contents but higher hydroxy radical scavenging rate. Compared to control, α-LA treatment enhanced enzymatic: superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR) as well as nonenzymatic antioxidants: glutathione (GSH) and ascorbate (AsA). Meanwhile, α-LA was protective against oxidative stress by inducing glutaredoxin (LcGrx), thioredoxin (LcTrx) and methionine sulfoxide reductase (LcMsr) expression levels. These α-LA-induced antioxidant systems directly increased the antioxidant capacity. Further research indicated that α-LA pretreatment maintained higher intracellular ATP level and activated extracellular ATP signaling through up-regulating LcDORN1s expression, indirectly increasing the antioxidant capacity. In conclusion, α-LA is effective to increase the antioxidant capacity and delay the pericarp browning of litchi fruit.

Effect of α-Lipoic Acid on the Development of Human Skin Equivalents Using a Pumpless Skin-on-a-Chip Model.

Owing to the prohibition of cosmetic animal testing, various attempts have recently been made using skin-on-a-chip (SOC) technology as a replacement for animal testing. Previously, we reported the development of a pumpless SOC capable of drug testing with a simple drive using the principle that the medium flows along the channel by gravity when the chip is tilted using a microfluidic channel. In this study, using pumpless SOC, instead of drug testing at the single-cell level, we evaluated the efficacy of α-lipoic acid (ALA), which is known as an anti-aging substance in skin equivalents, for skin tissue and epidermal structure formation. The expression of proteins and changes in genotyping were compared and evaluated. Hematoxylin and eosin staining for histological analysis showed a difference in the activity of fibroblasts in the dermis layer with respect to the presence or absence of ALA. We observed that the epidermis layer became increasingly prominent as the culture period was extended by treatment with 10 μM ALA. The expression of epidermal structural proteins of filaggrin, involucrin, keratin 10, and collagen IV increased because of the effect of ALA. Changes in the epidermis layer were noticeable after the ALA treatment. As a result of aging, damage to the skin-barrier function and structural integrity is reduced, indicating that ALA has an anti-aging effect. We performed a gene analysis of filaggrin, involucrin, keratin 10, integrin, and collagen I genes in ALA-treated human skin equivalents, which indicated an increase in filaggrin gene expression after ALA treatment. These results indicate that pumpless SOC can be used as an in vitro skin model similar to human skin, protein and gene expression can be analyzed, and it can be used for functional drug tests of cosmetic materials in the future. This technology is expected to contribute to the development of skin disease models.

Antioxidant Effect of α-Lipoic Acid on the Oxidation of Phosphatidylcholine Initiated by the Fenton Reaction

Mass spectrometry with negative-ion electrospray ionization proves the existence of not only monomers of α-lipoic acid (LA) but also its dimers and trimers in the aqueous phase. Upon incubation with ferrous ions (0.1 mM), new mass ions at m/z 261, 467, and 727 appear in the mass chromatogram in the positive ionization mode, and a mass ion at m/z 671 appears in the negative ionization mode. These mass ions are complexes of LA with ferrous ions, formed due to coordination bonds. The presence of complexes depends on the LA concentration. At concentrations of 0.25 to 4.00 mM, four complexes are observed. LA at a concentration of 4 mM (the maximum concentration that can be achieved by dissolving the acid in water) in the presence of 1 mM of hydrogen peroxide and 0.1 mM of Fe2+ inhibits phospholipid oxidation by 25%. Such an effect was not observed at the LA concentrations below 4 mM. At a concentration of 0.06 mM, only one complex with iron ions is formed (m/z 261). We found by IR spectroscopy that in the presence of iron ions and hydrogen peroxide, one or both sulfur atoms in the LA molecule are oxidized by the hydroxyl radical. The results suggest two mechanisms for the implementation of the antioxidant properties of LA: oxidation by a hydroxyl radical and chelation of ferrous ions.

Effect of α-lipoic acid on spatial memory and structural integrity of developing hippocampal neurons in rats subjected to sodium arsenite exposure

BackgroundExposure to arsenic has been reported to affect the nervous system in a number of ways. Various epidemiological studies suggest cognitive impairment in subjects following exposure to environmental arsenic. The goal of the present study was to determine if supplementation of exogenous α-lipoic acid (ALA) could ameliorate sodium arsenite (NaAsO2) induced adverse effects on learning and memory and synaptic connectivity in rat hippocampus. MethodsAccordingly, NaAsO2 alone (1.5/2.0 mg/kg bw) or NaAsO2 along with ALA (70 mg/kg bw) was administered by intraperitoneal (i.p.) route from postnatal day (PND) 4–17 to Wistar rat pups (experimental groups) and the Control groups received either distilled water or no treatment at all. After carrying out Elevated Plus Maze (EPM) and Morris Water Maze (MWM) test, the fresh brain tissues were collected on PND 18 and processed for Golgi Cox staining. ResultsObservations of MWM test revealed impaired learning and memory in iAs alone treated animals as against those co-exposed to iAs and ALA. In Golgi stained hippocampal sections of iAs alone treated animals, decreased dendritic arborization and reduced number of spines in pyramidal neurons (CA1) and granule cells (DG) was observed whereas neuronal morphology was preserved in the controls and ALA supplemented groups ConclusionsThese observations are suggestive of beneficial effects of ALA on iAs induced effects on learning and memory as well as on hippocampal neuronal morphology.

Comparative Characteristics of Dosage Forms of α-Lipoic Acid

α-Lipoic acid is a fatty acid, which in its physiological effect is on a par with vitamins and minerals, is a vitamin-like substance (vitamin N). A review of clinical trials of the effectiveness of α-lipoic acid in evidence-based diseases is presented. It is proved that the main indication for the use of α-lipoic acid is diabetes mellitus and complications associated with impaired glucose metabolism, including neuropathy, comprising children and adolescents. In addition, α-lipoic acid can be used for medicinal purposes and for a number of other diseases. α-Lipoic acid is an active substance with “critical bioavailability”: when introduced into the interior, its inter- and intra-individual plasma levels can vary significantly. Therefore, the therapeutic effectiveness of lipoic acid preparations largely depends on its form. A comparative characteristic of solid dosage forms of α-lipoic acid according to pharmacokinetic and clinical indicators is given. It was shown that the pharmacokinetic indices of the solid forms of α-lipoic acid practically do not differ, and the bioavailability of all forms is in the range of 30-60%. The advantages (for manufacturers and consumers / patients) and the disadvantages of α-lipoic acid drugs in solid forms - capsules and tablets are shown. Results proving the best therapeutic effect of α-lipoic acid in micellar form are presented.

Pharmacological Antagonism of T-Type Calcium Channels Constrains Rebound Burst Firing in Two Distinct Subpopulations of GABA Neurons in the Rat Ventral Tegmental Area: Implications for α-Lipoic Acid.

The ventral tegmental area (VTA) is a midbrain region highly involved in motivation and reward. A large body of work has investigated synaptic plasticity and ion channel excitability in this area, which has strong implication in drug abuse. We recently provided electrophysiological and pharmacological evidence that the CaV3.1 isoform of T-type voltage-gated calcium channels contributes to the excitability of VTA dopamine (DA) neurons. However, the role of T-channels in excitability of VTA gamma-amino-butyric acid (GABA) neurons remained unaddressed. Here, with a population study of rat VTA GABA neurons, we provide evidence that T-channels contribute to rebound spiking activity in two phenotypically distinct subpopulations of GABAergic neurons, each with differing electrophysiological characteristics. Additionally, we provide the first study to investigate the effect of α-lipoic acid (ALA) on ion channels in mesolimbic reward circuitry. Taken together, our population study and pharmacology experiments implicate T-channels as a target for therapies aimed at tempering VTA and mesolimbic circuit excitability.

Effects of α-lipoic acid on LPS-induced neuroinflammation and NLRP3 inflammasome activation through the regulation of BV-2 microglial cells activation

Microglial cells are known as the main immune cells in the central nervous system, both regulating its immune response and maintaining its homeostasis. Furthermore, the antioxidant α-lipoic acid (LA) is a recognized therapeutic drug for diabetes because it can easily invade the blood–brain barrier. This study investigated the effect of α-LA on the inflammatory response in lipopolysaccharide (LPS)-treated BV-2 microglial cells. Our results revealed that α-LA significantly attenuated several inflammatory responses in BV-2 microglial cells, including pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin (IL)-6, and other cytotoxic molecules, such as nitric oxide and reactive oxygen species. In addition, α-LA inhibited the LPS-induced phosphorylation of ERK and p38 and its pharmacological properties were facilitated via the inhibition of the nuclear factor kappa B signaling pathway. Moreover, α-LA suppressed the activation of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasomes, multiprotein complexes consisting of NLRP3 and caspase-1, which are involved in the innate immune response. Finally, α-LA decreased the genes accountable for the M1 phenotype, IL-1β and ICAM1, whereas it increased the genes responsible for the M2 phenotype, MRC1 and ARG1. These findings suggest that α-LA alleviates the neuroinflammatory response by regulating microglial polarization.

Effects of α-lipoic acid on chronic cerebrovascular hypoperfusion in an animal model of vascular dementia.

Given the aging population, the treatment of vascular dementia (VaD) is becoming increasingly important. The antioxidant α-lipoic acid (α-LA) protects against neurodegeneration in VaD, but the underlying mechanisms remain unclear. Hence, we aimed to identify the effects of α-LA on cognitive function following chronic cerebrovascular hypoperfusion in a VaD animal model. Mice were categorized into the sham, bilateral common carotid artery stenosis (BCAS), or BCAS + α-LA group. The BCAS + α-LA group was intraperitoneally injected (100 mg/kg) once daily with α-LA for 4 weeks after BCAS surgery, while the BCAS and sham groups were injected with saline. After the last injection, we examined cognitive function and exploration behavior using the Morris water maze. Mice brains were then harvested for Western blot analyses. The BCAS group, but not the BCAS + α-LA group, showed cognitive dysfunction in the Morris water maze. Apoptosis pathways involving poly (ADP-ribose) polymerase (PARP) cleavage, phosphorylated-mammalian target of rapamycin (p-mTOR), phosphorylated-3-phosphoinositide-dependent protein kinase-1, and phosphorylated-protein kinase B (p-AKT) were enhanced in the BCAS group than the α-LA group. The BCAS + α-LA group demonstrated less PARP cleavage and p-mTOR function than did the BCAS group. The activity of autophagy pathways involving LC3B was higher in the BCAS and BCAS + α-LA groups than the sham group, but there were no significant differences between the BCAS and BCAS + α-LA groups. In the BCAS rodent model, cognitive dysfunction and apoptosis mediated by the phosphatase and tensin homolog/AKT/mTOR pathway were observed in the hippocampus. However, acting on the mTOR pathway, α-LA improved cognitive function and led to hippocampal cell survival. Thus, α-LA may be useful for treating VaD.

Alpha lipoic acid and metformin alleviates experimentally induced insulin resistance and cognitive deficit by modulation of TLR2 signalling.

Obesity is commonly found to be co-morbid with type 2 Diabetes Mellitus. In obese diabetic patients, TLR-2 receptor induced inflammation leads to the development of insulin resistance (IR). Furthermore, the IR is considered to be the most important cause for promoting cognitive decline which is evident in brain of patients with Alzheimer's disease related dementia (ADRD). In this study, the effect of α-lipoic acid (ALA) has been examined in rodent model of zymosan induced insulin resistance and cognitive deficits, targeting at TLR-2 signalling. TLR-2 agonist, Zymosan initiates inflammatory cascade, resulting in IR and cognitive dysfunction. Zymosan (50 mg/kg ip) was given to mice on 1st, 8th, 15th and 22nd day to induce IR which was confirmed by hyperglycaemia, hyperinsulinemia, hyperlipidimea, increased glycated haemoglobin and HOMA-IR. Further the cognitive performance was assessed in Morris water maze revealing cognitive deficit in zymosan treated mice. Daily treatment with ALA for 28 days (50, 100, 200 mg/kg, ip) significantly improved insulin sensitivity and cognitive performance in mice by decreasing insulin resistance, corticosterone, IL-6 levels, acetylcholinesterase enzyme activity and oxidative stress in liver, cortex and hippocampus. ALA also increased adiponectin level and reduced body weight. Combination of ALA (100 mg/kg, ip) with metformin (100 mg/kg, ip) exhibited a potentiating effect in improving cognitive performance and insulin signalling. The findings of the study supported the hypothesis that TLR-2 induced inflammation leads to insulin resistance and cognitive impairment and provides an evidence for the therapeutic effect of ALA in IR and ADRD patients.

Effects of α-lipoic acid on oxidative stress markers in type 2 diabetes patients with nonalcoholic fatty liver disease

Objective To study the serum levels of oxidative stress markers in the new type 2 diabetes mellitus(T2DM) patients with nonalcoholic fatty liver disease(NAFLD), and the effect of α-lipoic acid(A-LA) on oxidative stress markers. Methods From August 2016 to August 2017, 80 new T2DM patients complicated with NAFLD (T2DM + NAFLD group) and 80 new T2DM patients without NAFLD (T2DM group) admitted to Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University were selected.The serum levels of Fasting blood glucose(FPG), body mass index(BMI), triglyceride(TG), total cholesterol(TC), high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C), insulin resistance index(HOMA-IR), serum superoxide dismutase(SOD), serum malondialdehyde(MDA), glutathione peroxidase(GSH-PX) were detected and compared between the two groups.And then, the T2DM patients with NAFLD were treated by A-LA for two weeks.The SOD, MDA, GSH-PX levels were compared before and after treatment. Results The FPG, BMI, TG, HOMA-IR of the T2DM+ NAFLD group were (10.71±3.63)mmol/L, (27.08±3.87)kg/m2, (3.40±1.85)mmol/L, (5.40±2.98), respectively, which were significantly higher than those of the T2DM group[(9.50±3.78)mmol/L, (23.58±2.75)kg/m2, (1.79±1.44)mmol/L, (2.41±1.18)](t=2.022, 6.603, 2.829, 4.157, all P 0.05). The level of MDA in the T2DM+ NAFLD group was (5.11±0.25)μmol/L, which was significantly higher than (4.56±0.28)μmol/L in the T2DM group(t=2.106, P<0.05). The levels of SOD, GSH-PX, SOD/MDA in the T2DM+ NAFLD group were (77.42±10.31)U/mL, (69.62±9.24)U, (15.39±2.23), respectively, which were significantly lower than those in the T2DM group[(93.26±11.21)U/mL, (87.54±9.58)U, (20.33±2.93)](t=2.455, 2.653, 3.148, all P<0.05). After treatment with A-LA, the MDA level of the T2DM+ NAFLD group was (4.81±0.26)μmol/L, which was significantly lower than that before treatment[(5.11±0.25)μmol/L, t=2.117, P<0.05], the levels of SOD, GSH-PX, SOD/MDA of the T2DM+ NAFLD group were (87.15±10.88)U/mL, (78.73±9.57)U, (18.05±2.51), respectively, which were significantly higher than those before treatment(t=2.117, 2.207, 2.228, 3.148, all P<0.05). Conclusion A-LA might prove usefully in the treatment of patients with T2DM and NAFLD by change the oxidative stress. Key words: Diabetes mellitus, Type 2; Fatty liver; Oxidative stress; Thioctic acid

Impact of dietary lipoic acid supplementation on liver mitochondrial bioenergetics and oxidative status on normally fed Wistar rats

The aim of this study was to examine the effects of α-lipoic acid (α-LA) on liver mitochondrial bioenergetics and oxidative status for 8 weeks in normal-healthy animals. A pair-fed group was included to differentiate between α-LA direct effects and those changes due to reduced food intake. α-LA decreased body weight gain, liver weight and insulin levels with no differences compared to its pair-fed group. α-LA significantly reduced energy efficiency, the activity of the electron transport chain complexes and induced a lower efficiency of oxidative phosphorylation with reduced ATP production. α-LA supplementation directly decreased plasma triglycerides (TGs), free fatty acids and ketone bodies levels. A significant reduction in hepatic TG content was also observed. A significant up-regulation of Cpt1a, Acadl and Sirt3, all β-oxidation genes, along with a significant deacetylation of the forkhead transcription factor 3a (FOXO3A) was found in α-LA-treated animals. Thus, α-LA along with a standard chow diet has direct actions on lipid metabolism and liver by modulating mitochondrial function in normal-weight rats. These results should be taken into account when α-LA is administered or recommended to a healthy population.

Alpha-lipoic acid alleviates the 6-OHDA-induced SH-SY5Y cell damage by inhibiting autophagy via AMPK/mTOR pathway

Objective To investigate the effects of α-lipoic acid(ALA)on 6-hydroxydopamine(6-OHDA)-induced autophagy in human neuroblastoma(SH-SY5Y)cells and its possible mechanisms. Methods SH-SY5Y cells were divided into 5 groups: blank control group(group A), ALA group(group B), 6-OHDA group(group C), ALA+ 6-OHDA group(group D), and rapamycin(RAPA)group(group E). The cell viability, cell apoptosis, and oxidative stress were assayed and analyzed in A-D group.The expression of autophagy-related proteins LC3-Ⅱ, AMP-activated protein kinase(AMP-K), phosphorylated AMPK(p-AMPK), the mammalian target of rapamycin(mTOR)and p-mTOR were detected by Western blot in A-E group. Results Compared with the blank control group, the 6-OHDA group significantly reduced the cell viability(P<0.01)and p-mTOR protein expression(P<0.05), and increased the cellular apoptosis rate(P<0.01), oxidative stress level(P<0.01), LC3-Ⅱ protein expression(P<0.05, with the highest level at 6 h after treatment), and p-AMPK protein expression(P<0.05). There was no significant difference in these indices between ALA group and the blank control group.Compared with 6-OHDA group, ALA+ 6-OHDA group showed that the cell viability(P<0.01)and p-mTOR protein expression(P<0.05)were increased, while the cellular apoptosis rate(P<0.01), oxidative stress level(P<0.01), LC3-Ⅱ protein expression(P<0.05), and p-AMPK protein expression(P<0.05)were decreased. Conclusions The 6-OHDA can induce oxidative stress and autophagy in SH-SY5Y cells and decrease the cell viability.ALA can alleviate the 6-OHDA-induced cell injury possibly by inhibiting autophagy via AMPK/mTOR pathway. Key words: Parkinson's disease; Autophagy; α-lipoic acid; Oxidative stress

Effects of α-lipoic acid on growth performance, body composition, antioxidant status and lipid catabolism of juvenile Chinese mitten crab Eriocheir sinensis fed different lipid percentage

This study evaluates the effects of dietary lipid percentage (7% and 13%) on growth performance, body composition, antioxidative status and hepatopancreas lipid catabolism of Chinese mitten crab Eriocheir sinensis. Each lipid diet was supplemented with three concentrations of α-lipoic acid at 0, 700 and 1400mg/kg, and fed to E. sinensis juveniles for eight weeks. The weight gain and specific growth rate of crabs fed the diets supplemented with α-LA were significantly higher than those fed the control diet without α-LA, regardless of dietary lipid percentage. The α-LA significantly increased lipid accumulation in the whole body and hepatopancreas in a dose-dependent manner. Crabs fed 13% lipid showed a significantly higher hepatosomatic index than those fed 7% lipid. The mRNA expressions of triacylglycerol lipase and intracellular lipase increased with the increase of α-LA concentration in crabs fed 7% lipid. No significant difference was found in the CPT-1 mRNA expression among all treatments. The α-LA supplementation at 1400mg/kg significantly improved oxidative stress due to lipid accumulation in the hepatopancreas of crabs fed 7% lipid as indicated by the high activity of superoxide dismutase and glutathione peroxidase and a low level of malondialdehyde. The diet with 13% lipid increased the lipid content in the hepatopancreas but suppressed glutathione peroxidase. Meanwhile, the total antioxidant capacity increased with the increase of α-LA concentration in crabs fed 13% lipid. This study indicates that α-LA supplementation can improve growth performance and accelerate lipid accumulation in the hepatopancreas by increasing lipid utilization efficiency. Furthermore, α-LA can relieve hepatopancreas oxidative damage induced by lipid accumulation and improve the health of E. sinensis.

Protective Effects of α-Lipoic Acid Alone and in Combination with Ferulic Acid in Diabetes Induced Nephropathy in Rats: A Biochemical and Histoarchitecture study

Protective Effects of α-Lipoic Acid Alone and in Combination with Ferulic Acid in Diabetes Induced Nephropathy in Rats: A Biochemical and Histoarchitecture study

Neuroprotective effects of α-lipoic acid against hypoxic– ischemic brain injury in neonatal rats

Purpose: To explore the neuroprotective efficacy of α-lipoic acid (ALA) against hypoxic-ischemic encephalopathy (HIE) in neonatal rats. Methods: Forty-eight rats (P7-pups) were randomly assigned to one of four groups: group I received saline; group II (HI) underwent unilateral carotid artery ligation and hypoxia (92 % N2 and 8 % O 2 ) for 2.5 h; and groups III and IV (ALA 50 and 100) were treated with 50 or 100 mg ALA/kg for 7 days prior to against hypoxic-ischemic (HI) insult. Cerebral antioxidant status, edema, and the levels of inflammatory markers were determined. Results: ALA administration substantially (p < 0.01) attenuated both cerebral infarct area and degree of edema while decreasing the levels of several inflammatory markers (TNF-α, NF-p65, IL-1β, IL-6). In addition, in the ALA groups, antioxidant enzyme (SOD, CAT, GSH) activities were significantly elevated, while the expressions of TNF-α and IL-1β protein were significantly (p < 0.01) down-regulated. Conclusion: The neuroprotective efficacy of ALA in HIE can be attributed to its suppression of both oxidative stress and the levels of inflammatory markers. Keywords: Hypoxic–ischemic brain injury, α-Lipoic acid, Cerebral infarct area, Edema, Antioxidants, Inflammatory markers