Effect Of Alpha-lipoic Acid Research Articles

The Effect of Alpha Lipoic Acid on the Recovery of Sciatic Nerve Injury in Rats: A Prospective Randomized Controlled Trial.

The aim of this study was to investigate the regenerative effects of alpha lipoic acid on the recovery of sciatic nerve crush injury (SNCI) in rats. This was a randomized, experimental, and sham-controlled study. The sciatic nerves of 28 rats in four groups were traumatized for 60 secs: G1, sham operated + saline; G2, SNCI + saline; G3, SNCI + alpha lipoic acid 50 mg/kg/day; and G4, SNCI + alpha lipoic acid 100 mg/kg/day. Sciatic functional index values were measured on day 0, 1, 7, 14, 21, and 28. Sciatic nerve stimulation threshold values were recorded on day 1, 14, and 28. End-point histopathologic evaluation was conducted. The mean sciatic functional index value of G2 but not G3/G4 on day 7 was significantly lower than on day 0 (P = 0.035, P = 0.447/P = 0.800). The mean sciatic functional index value of G2 but not G3/G4 increased significantly between day 7 and 14 (P = 0.035, P = 0.447/P = 0.438). The day 14 mean sciatic nerve stimulation threshold values of G3/G4 but not G2 were decreased significantly compared with those on day 1 (P = 0.022/P = 0.022, P = 0.933). The mean sciatic nerve stimulation threshold values of G3/G4 on day 14 were similar to those on day 0 (P = 0.106/P = 0.418). Regeneration in muscle and nerve connective tissues and nerve structures was observed in G3/G4. Inflammation in the muscle and nerve tissues of G4 was suppressed down to similar levels of G1. Myelinated nerve fibers were less degenerated in G3/G4. Alpha lipoic acid has the potential to accelerate the process of nerve healing in the context of SNCI in rats.

Hepatocurative Effects of Alpha Lipoic Acid in 5-Fluorouracil-Induced Toxicity Involves Activation of TNF Alpha and NF-?? Signaling Pathway

Hepatocurative Effects of Alpha Lipoic Acid in 5-Fluorouracil-Induced Toxicity Involves Activation of TNF Alpha and NF-?? Signaling Pathway

Effect of Alpha Lipoic Acid on Polycystic Ovary Syndrome with Insulin Resistance

Effect of Alpha Lipoic Acid on Polycystic Ovary Syndrome with Insulin Resistance

Stereological Study of the Protective Effect of Alpha-Lipoic Acid on Kidney Tissue following Toxicity with Silver Nanoparticles in NMRI Mice

Stereological Study of the Protective Effect of Alpha-Lipoic Acid on Kidney Tissue following Toxicity with Silver Nanoparticles in NMRI Mice

The effect of alpha lipoic acid on passive avoidance and social interaction memory, pain perception, and locomotor activity in REM sleep-deprived rats.

Evidence shows the vital role of sleep in the modulation of cognitive functions. Sleep deprivation (SD) can disrupt learning and memory processes. SD also affects pain perception and locomotor activity. Furthermore, alpha lipoic acid (ALA) may induce antioxidant and neuroprotective effects. ALA affects memory processes, pain subthreshold, and locomotor activity. The goal of the present study was to investigate the effect of REM (rapid-eye movement) SD and ALA on social and passive avoidance memory, locomotor activity, and pain perception. Multiple-platform apparatus was used to induce REM SD for 24h. Three-chamber paradigm test, the shuttle box, locomotion apparatus, and hot plate were used to assess social interaction memory, passive avoidance memory, locomotor activity, and pain perception, respectively. ALA was injected intraperitoneally at the doses of 35 and 70mg/kg. 24h REM SD impaired both types of memory. In addition, ALA (35mg/kg) reversed REM SD-induced memory impairments. However, ALA (70mg/kg) impaired social memory with no effect on REM SD-induced memory impairments. ALA (70mg/kg) also decreased pain subthreshold in REM SD rats. REM SD impairs social interaction and passive avoidance memory. Furthermore, ALA may exhibit a dose-dependent manner in some cognitive tasks. ALA can induce a therapeutic effect at one dose, and an impairment effect at another dose (lower or higher), while the cognitive task and the conditions are equal.

Alpha lipoic acid attenuates iron induced oxidative acute kidney injury in rats

ABSTRACT Iron has been implicated in oxidative tissue injury owing to its ability to generate reactive oxygen species (ROS). We investigated the reno-protective effects of alpha lipoic acid (ALA) by investigating its effects on the kidney isoform of NADPH oxidase (Nox4) and the specific signaling pathways, p38 MAPK and PI3K/Akt, which participate in apoptosis and survival, respectively. We established four groups of seven rats: control, 100 mg/kg ALA, 80 mg/kg iron sucrose (IS) and IS + ALA. IS and ALA were injected intravenously and rats were sacrificied after 6 h. The mRNA expression of the subunits of NADPH oxidase, Nox4 and p22phox; tumor necrosis factor-alpha (TNF-α); and kidney injury molecule-1 (KIM-1) were measured using quantitative real time polymerase chain reaction (qRT-PCR). Active caspase-3 protein expression was evaluated by immunostaining. Also, p38 MAPK and PI3K/Akt signaling pathways were analyzed using western blot. ALA suppressed the mRNA expression of Nox4, p22phox, TNF-α and KIM-1. Active caspase-3 protein expression induced by IS was decreased by ALA. ALA also suppressed p38 MAPK and activated the PI3K/Akt signaling pathway following IS administration. We found that ALA may be an effective strategy for preventing oxidative acute kidney injury caused by IS.

Effect of alpha-lipoic acid during preimplantation development of cattle embryos when there were different in vitro culture conditions

In many species, alpha-lipoic acid (ALA) is essential for embryo development. There, therefore, was investigation of effects of ALA supplementation to culture media for in vitro development of cattle embryos. In Experiment I, there were assessments of embryo production and oxidative status of cattle embryos derived by in vitro maturation and fertilization (IVM/IVF)that were cultured until the blastocyst stage of development using different ALA concentrations (5, 25 and 100 μM), fetal bovine serum (FBS) and amino acids (aa) as well as 20 % oxygen (O2) in the culture atmosphere. In Experiment II, embryos were cultured without FBS, at different ALA concentrations (2.5, 5 and 7.5 μM) and in the presence or absence of aa when there was a 7 % O2 atmosphere. Embryo development rates and blastocyst quality were evaluated. With 20 % O2 concentration, treatment with 100 μM ALA resulted in lesser hatching rates and development to the blastocyst stage (P < 0.01), while with supplementation with 5 μM ALA there were lesser (P = 0.04) glutathione concentrations and greater protein contents of embryos (P < 0.01). Culturing in the 7 % O2 atmosphere, combined with supplementation with 2.5 μM ALA with FBS and aa resulted in a greater blastocyst cell number (P = 0.03) and lesser hatching rates (P = 0.04). Taken together, results indicate supplementation with the greater ALA concentrations resulted in impairment of embryo development, regardless of the O2 concentration imposed during the culture period, while the relatively lesser supplementation-concentrations with ALA led to improvements in embryo quality.

The Histological Alteration of Proximal Part of Aorta Exposed to (MSG) and Protective Effect of an a Lipoic Acid (ALA) in Male Rabbits

Background. Monosodium Glutamate is one of the most world’s most widely used food additives. Its toxic effect have been shown in numerous animal studies, in which study MSG effects on cardiovascular system, therefore, This study was aimed to investigate the effect of alpha lipoic acid(ALA) on the damage in the large blood vessels induce by Mono sodium glutamate. Thirty two male rabbits was divided equally and randomly into four groups as following. Control group in which rabbits where fed with normal diet without supplementation, second group was gived MSG orally (8mg/kg.BW), While animals of third group were given ALA orally (60mg/kg.BW) while animal in fourth group were given orally (MSG 8mg/kg.bw and ALA 60mg/kg.bw), all treatment are extended to 8 weeks. The outcomes of research revealed a significant increased (p&lt;0.05) in aortic medial layer thickness in animals administration of MSG in a comparesion with control and groups treated and distortion structure of laminar fibers, endothelial cells lost normal squamous. In addition, there is a significant decreased (p&lt;0.05) in medial tunica thicken in animals used ALA combination with MSG, so we noted return the disarranged of architecture tissue near.

Supplementation of freezing media with alpha lipoic acid preserves the structural and functional characteristics of sperm against cryodamage in infertile men with asthenoteratozoospermia

The aim of this study was to examine the effects of alpha lipoic acid (ALA) supplementation during semen cryopreservation on the sperm quality, chromatin integrity, oxidative stress, and expression level of BAX, BCL2, HSP70 and iNOS genes in semen samples obtained from infertile men with asthenoteratozoospermia. MethodsTwenty freshly ejaculated semen samples were cryopreserved with sperm freezing medium supplemented with 0.00, 0.02, 0.05, 0.1, 0.5, and 1 mmol/mL of ALA. The samples were analyzed according to the WHO guidelines before and after freezing. Sperm ROS production level, DNA fragmentation and cryo-capacitation were assessed using flow cytometry, TUNEL assay and chlortetracycline (CTC) test, respectively. Expression level of stress protein (HSP70), pro-apoptotic Bax, anti-apoptotic Bcl-2, and iNOS genes was assessed by real-time PCR assay. ResultsThe effective concentrations of ALA (0.02 and 0.5 mM) significantly improved the motility, viability and morphology of the frozen-thawed sperms compared to the control group treated with 0.00 mM of ALA. During cryopreservation, treatment of semen with 0.02 mM of ALA, as the optimal concentration, significantly decreased DNA fragmentation and oxidative stress level (P < 0.05), protected the acrosome integrity, and led to insignificant reduction in BAX gene expression level and significant increase in expression level of BCL2, HSP70, and iNOS genes compared with control group. ConclusionOur findings revealed that the adding ALA to semen samples obtained from infertile men with asthenoteratozoospermia plays a significant protective role against cryodamage by preserving the sperm functional parameters.

Effect of Alpha-Lipoic Acid on Blood Hormonal Parameters and Follicular Fluid Oxidative Stress Factors in Infertile Women with Polycystic Ovary Syndrome Undergoing Intracytoplasmic Sperm Injection

Effect of Alpha-Lipoic Acid on Blood Hormonal Parameters and Follicular Fluid Oxidative Stress Factors in Infertile Women with Polycystic Ovary Syndrome Undergoing Intracytoplasmic Sperm Injection

Ameliorative effect of alpha lipoic acid and royal jelly against the side effects of cyclophosphamide in liver of albino rats

BackgroundCyclophosphamide (CP) is a cytotoxic anticancer drug used for the treatment of neoplastic diseases. The present study aimed to examine biochemical, histological, and ultrastructural effects of CP on rat liver and determine the hepatoprotective effects of alpha-lipoic acid (LA) or royal jelly (RJ) against CP.ResultsThe present study revealed that CP-induced significant increase in hepatic marker enzymes (ALT and AST), and elevation in malonaldehyde (MDA) was concomitant with a significant decrease of superoxide dismutase (SOD). It caused histopathological changes in the liver of rat including vacuolation, infiltration, degeneration, and necrosis. Ultrastructurally, the hepatocytes appeared degenerated with multiple small- and medium-sized lipid droplets in the cytoplasm. Kupffer cell showed a shrunken nucleus. Administration of LA and RJ resulted in an obvious improvement in the altered level of ALT, AST, MDA, and SOD activities when compared with the CP-treated group in addition to marked amelioration in histopathology and ultrastructure of the liver.ConclusionsLA is markedly effective than RJ in protecting rats against CP-induced biochemical, histopathological, and ultrastructural changes. This protection may be due to its antioxidant properties and scavenging abilities against active free radicals.

The protective effect of alpha lipoic acid (ALA) on social interaction memory, but not passive avoidance in sleep-deprived rats.

Sleep is involved in maintaining energy, regulating heat, and recovering tissues. Furthermore, proper cognitive functions need sufficient sleep. Many studies have revealed the impairment effect of sleep deprivation (SD) on cognitive functions including learning and memory. Alpha lipoic acid (ALA) is a potent free radical scavenger, biological antioxidant, and neuroprotective agent. Furthermore, ALA improves learning and memory performance, decreases oxidative stress, and enhances antioxidant biomarkers. In this study, we aimed to investigate the effect of ALA on social interaction and passive avoidance memories in sleep-deprived rats. Total sleep deprivation (TSD) apparatus was used to induce SD (for 24h). Three-chamber paradigm test and shuttle box apparatus were used to evaluate social interaction and passive avoidance memory, respectively. Rats' locomotor apparatus was used to assess locomotion. ALA was administered intraperitoneally at doses of 17 and 35mg/kg for 3 consecutive days. The results showed SD impaired both types of memories. ALA at the dose of 35mg/kg restored social interaction memory in sleep-deprived rats; while, at the dose of 17mg/kg attenuated impairment effect of SD. Moreover, ALA at the dose of 35mg/kg impaired passive avoidance memory in sham-SD rats and at both doses did not rescue passive avoidance memory in sleep-deprived rats. In conclusion, ALA showed impairment effect on passive avoidance memory, while improved social interaction memory in sleep-deprived rats.

Inhibitory effect of alpha-lipoic acid on mitochondrial dysfunction and interleukin-8 expression in interleukin-1beta-stimulated ataxia teleangiectasia fibroblasts.

Ataxia telangiectasia (A-T) is an inherited neurodegenerative disease caused by mutation in the ataxia telangiectasia mutated (ATM) gene, leading to loss of function in the encoded protein ATM. Because ATM functions to reduce oxidative stress by up-regulating antioxidant enzymes, oxidative stress is a prevalent A-T phenotype and a mediator of the inflammation that drives A-T pathology. Reactive oxygen species (ROS) levels and the expression of pro-inflammatory cytokine interleukin-8 (IL-8) were higher in A-T cells than in normal cells. ROS are related to mitochondrial dysfunction and activation of nuclear factor kappa B (NF-κB) to induce IL-8 expression. Alpha-lipoic acid (α-LA), a naturally occurring thiol compound, shows an antioxidant effect in various cells. This study is aimed to determine if α-LA confers protection against NF-κB activation, IL-8 expression, and mitochondrial dysfunction in A-T cells which are exposed to the inflammatory cytokine IL-1β. A-T fibroblasts were treated with or without α-LA. The levels of intracellular and mitochondrial ROS, mRNA and protein levels of IL-8, mitochondrial membrane potential (MMP), ATP levels, and DNA binding activity of NF-κB were determined. As a result, IL-1β increased NF-κB activation, IL-8 expression, intracellular and mitochondrial ROS levels, but decreased MMP and ATP level in A-T cells. Pretreatment of A-T cells with α-LA inhibited IL-1β-induced activation of NF-κB, IL-8 expression, and mitochondrial dysfunction by reducing ROS levels. In conclusion, supplementation with α-LA may be beneficial for reducing the oxidative stress-induced mitochondrial dysfunction and IL-8 production associated with A-T.

Protective Effect of Alpha-Lipoic Acid on Salivary Dysfunction in a Mouse Model of Radioiodine Therapy-Induced Sialoadenitis.

Radioiodine (RI) therapy is known to cause salivary gland (SG) dysfunction. The effects of antioxidants on RI-induced SG damage have not been well described. This study was performed to investigate the radioprotective effects of alpha lipoic acid (ALA) administered prior to RI therapy in a mouse model of RI-induced sialadenitis. Four-week-old female C57BL/6 mice were divided into four groups (n = 10 per group): group I, normal control; group II, ALA alone (100 mg/kg); group III, RI alone (0.01 mCi/g body weight, orally); and group IV, ALA + RI (ALA at 100 mg/kg, 24 h and 30 min before RI exposure at 0.01 mCi/g body weight). The animals in these groups were divided into two subgroups and euthanized at 30 or 90 days post-RI treatment. Changes in salivary 99mTc pertechnetate uptake and excretion were tracked by single-photon emission computed tomography. Salivary histological examinations and TUNEL assays were performed. The 99mTc pertechnetate excretion level recovered in the ALA treatment group. Salivary epithelial (aquaporin 5) cells of the ALA + RI group were protected from RI damage. The ALA + RI group exhibited more mucin-containing parenchyma and less fibrotic tissues than the RI only group. Fewer apoptotic cells were observed in the ALA + RI group compared to the RI only group. Pretreatment with ALA before RI therapy is potentially beneficial in protecting against RI-induced salivary dysfunction.

Manganese-induced neurotoxicity and the potential protective effects of lipoic acid and Spirulina platensis

Manganese (Mn) is essential for many physiological processes; however, its excessive accumulation in the brain causes severe dysfunctions in the nervous system. Oxidative stress is thought to be involved in Mn‐induced neurotoxicity. The aim of this study was to evaluate the neurotoxic effects of Mn and the potential protective effects of alpha lipoic acid (ALA) and Spirulina platensis (SP), each alone and in combination. Sixty-four male albino rats were divided into eight equal groups: group 1 was used as control, group 2 received saline, which used as a vehicle, group 3 received ALA (50 mg/kg/day), group 4 received SP (300 mg/kg/day), group 5 received Mn (74 mg/kg, 5 days/week), group 6 received Mn + ALA, group 7 received Mn + SP, group 8 received Mn + ALA + SP. Groups 6, 7 and 8 received the same previously mentioned doses. All treatments were orally gavaged for 8 weeks. Mn administration caused neurobehavioral changes, increases of brain and serum Mn and malondialdehyde (MDA), with decreased glutathione peroxidase (GPx), dopamine and acetylcholine levels. The co-treatment with ALA and SP revealed their ability to protect against oxidative damage, neurobehavioral and biochemical changes induced by Mn.

SO044ALPHA LIPOIC ACID COMPARED TO SELENIUM IN MITOCHONDRIAL RESUSCITATION AND MI RNA-126 EXPRESSION IN HEMODIALYSIS PATIENTS

Abstract Background and Aims anti-oxidants may decrease the risk of cardiovascular complications (CVC) in HD patients. We aimed to study antioxidant effect of Alpha lipoic acid and selenium on oxidative stress, endothelial repair, and mitochondrial functions in HD patients by evaluating the serum level of reactive oxygen species (ROS), miRNA-126, and CoQ10. Method 60 individuals were enrolled and randomized into 3 groups, G1; 22 HD patients as control, G2; 20 HD patients received Selenium, and G3;18 HD patients received. Serum levels of ROS, CoQ10, and miRNA-126 were assessed at base line and after three months treatment for all patients. Results At baseline, all groups were matched regarding their demographic data and target parameters. After three months, in G1; the serum level of ROS increased significantly (P &amp;lt; 0.05), CoQ10 didn't change significantly (P &amp;gt; 0.05), while the fold expression of miRNA-126 decreased significantly (P &amp;lt; 0.05). In G2,3; there were statistical significant changes in target parameters after the treatment, ROS level decreased significantly by 34%, and by 79%, CoQ10 mean levels increased significantly from 13.21 to 28.35, and from 13.46 to 36.43 ng/ml, mean fold expression of miRNA126, increased significantly by 6.94, and 10.54 folds, in Selenium and, Thiotacid groups respectively. The results showed that Thiotacid was better than Selenium in ROS level reduction, and CoQ10 level improvement, while no statistical significant difference between two drugs regarding miRNA126 level (P &amp;gt; 0.05). Conclusion Selenium and, Thiotacid reduce oxidative stress and also they enhancing the endothelial repairing, and improve mitochondrial functions and thus may reduce risk of CVC.

Histopathological Assessment of Hepato-Nephrotoxicity Induced by Nano Copper Particles in Adult Male Albino Rats and the Potential Protective Effect of Alpha Lipoic Acid: A Chronic Study

Background: Copper nanoparticles (CNPs) have unique physical and chemical properties for this reason it was widely used in various medical and non-medical applications. This study aimed to study the toxic effect of copper nanoparticles on liver and kidney through histopathological examination of liver and kidney tissues and if there is improvement of hepato-nephrotoxicity after cessation of exposure and to study the potential protective effect of alpha lipoic acid (ALA) against hepato-nephrotoxicity induced by copper nanoparticles. Finding: Histopathological examination of liver and kidney tissues in rats received CNPs showed significant alteration, cessation of exposure can cause slight improvement and ALA can cause significant improvement. Conclusion: Copper Nanoparticles have hepato-nephrotoxic effect and ALA can be safely used as a protective agent against CNPs toxicity.

Effect of alpha-lipoic acid on oxidative stress, viability and motility in the common carp (Cyprinus carpio) spermatozoa after short-term storage and cryopreservation

As known for different metabolic functions, α-lipoic acid (ALA) has been tested for spermatozoa preservation of animals as well as of human, but not for fish spermatozoa. The present study determined the effects of ALA on short and long-term (cryopreservation) preservation of common carp (Cyprinus carpio) spermatozoa, for the first time. For that, spermatozoa were diluted in extenders containing 0 (control), 0.025, 0.05, 0.1, 0.5, 1, 2, 5, and 10 mM of ALA concentrations in both short-term preservation and cryopreservation. Spermatozoa motility parameters by computer-assisted semen analysis, viability, lipid peroxidation and catalase activity in spermatozoa were conducted in both 2nd and 120th hours of short-term storage and post-thaw samples. Higher percentages of total spermatozoa motility (80 ± 3) and viability (87 ± 3) were observed in 0.5 mM ALA group after 120 h of incubation. In post-thaw samples, higher percentages of these parameters were in 1 mM ALA group (74 ± 3 and 83 ± 2, respectively). Moreover, the results have shown that the addition of ALA until concentrations of 2 mM improved especially spermatozoa curvilinear velocity, maintained viability, and suppressed excessive lipid peroxidation during the preservations. In conclusion, the additions of 0.5 mM ALA for short-term preservation and 1 mM ALA for cryopreservation were the optimal concentrations, and shown the protective effects on common carp spermatozoa, when considering all measured parameters together.

Effects of alpha lipoic acid as a supplement in obese children and adolescents

ObjectivesObesity is significantly associated with inflammatory process and oxidative stress. Alpha lipoic acid (ALA) is a potent antioxidant that has been reported for reducing weight in animals and obese adults in several studies but no data are available in pediatrics. We investigated the possible beneficial role of ALA in obese children. Patients and methodsEighty obese children and adolescents were randomized into two groups; the treatment group (n = 40) who received 300 mg of ALA twice daily for 3 months and the control group (n = 40) who received placebo for 3 months. Measurements of weight, body mass index (BMI), lipid profile, fasting blood glucose (FBG), malondialdhyde (MDA), tumor necrosis factor alpha (TNF-α), leptin and adiponectin were carried out before and 3 months after the treatment. ResultsALA treatment group had a significant reduction of the weight, BMI, MDA, TNF-α, and leptin levels but a significant increase of adiponectin level (P < 0.05) compared to the control group. However, it had no effect on FBG or lipid profile (P > 0.05). ConclusionALA may be a promising supplement in the weight reduction in obese children and adolescents.

Effects of Alpha-Lipoic Acid on TGF-β1 and Urotensin-II Levels in Glucocorticoid-Induced Osteonecrosis in Rats

Background: Osteonecrosis (ON) is a serious health problem, which dramatically reduces the quality of life. Objectives: In the present study on the rat model of glucocorticoids (GCs) -induced ON, we explored the influence of alpha-lipoic acid on serum levels of TGF-β1 and urotensin-II (U-II) and on histological alteration with respect to fatty degeneration and osteocyte necrosis. Methods: A total of 32 male Wistar albino rats were equally assigned to four groups, including control, methylprednisolone acetate (MPA), alpha-lipoic acid (ALA), and MPA with ALA (MP1 + ALA). The animals in MPA group subcutaneously received 15 mg/kg/week during 2 weeks, whereas 100 mg/kg/day ALA was intraperitoneally administered to ALA group during 4 weeks. The MPA + ALA group had both treatments with the same doses. ON was confirmed and graded histologically. Lipid peroxidation and DNA damage levels were immunohistochemically assessed in rats’ bones. Results: After histopathological examinations, ALA injection attenuated oxidative stress levels through reducing both 8-OHdG-and 4-HNE-positive cells in the femoral head region (P < 0.05). The U-II and TGF-β1 protein levels significantly decreased after ALA treatment in MPA injected animals (P < 0.05, P < 0.01, respectively). Moreover, there was a strong correlation between U-II and TGF-β1 protein levels (P = 0.019, r = 0.884). Conclusions: This study is novel with regard to showing the therapeutic effects of ALA on GC-induced ON in rats as well as the strong correlation between the expression levels of U-II and TGF-β1 proteins. In this regard, ALA may be a therapeutic agent in the treatment of ON patients.