Alpha-lipoic Acid Treatment Research Articles

Cardiovascular and Renal Effects Induced by Alpha-Lipoic Acid Treatment in Two-Kidney-One-Clip Hypertensive Rats.

α-Lipoic acid (LA) is an antioxidant of endogenous production, also obtained exogenously. Oxidative stress is closely associated with hypertension, which causes kidney injury and endothelial dysfunction. Here, we evaluated the cardiovascular and renal effects of LA in the two-kidney-one-clip (2K1C) hypertension model. The rats were divided into four groups: Sham surgery (Sham), the two-kidneys-one-clip (2K1C) group, and groups treated with LA for 14 days (Sham-LA and 2K1C-LA). No changes were observed in the pattern of food, water intake, and urinary volume. The left/right kidney weight LKw/RKw ratio was significantly higher in 2K1C animals. LA treatment did not reverse the increase in cardiac mass. In relation to vascular reactivity, there was an increase in the potency of phenylephrine (PHE) curve in the hypertensive animals treated with LA compared to the 2K1C group and also compared to the Sham group. Vasorelaxation induced by acetylcholine (Ach) and sodium nitroprusside (SNP) were not improved by treatment with LA. Urea and creatinine levels were not altered by the LA treatment. In conclusion, the morphological changes in the aorta and heart were not reversed; however, the treatment with LA mitigated the contraction increase induced by the 2K1C hypertension.

Alpha-Lipoic Acid Ameliorates Impaired Steroidogenesis in Human Granulosa Cells Induced by Advanced Glycation End-Products.

Ovarian granulosa cells (GCs) are essential for follicular development. Ovarian advanced glycation end-products (AGEs) accumulation is related to GCs dysfunction. Alpha-lipoic acid (ALA) illustrates therapeutic capabilities for infertility-related disorders. Therefore, this study assessed the effects of ALA on AGEs-induced GCs hormonal dysfunction. The study was conducted from October 2021 to September 2022 at the Department of Medical Genetics, Shiraz University of Medical Sciences. Isolated GCs (n=50) were divided into control, human glycated albumin (HGA), HGA+ALA, and ALA treatments. Steroidogenic enzymes and AGE receptor (RAGE) genes were assessed by qRT-PCR. Steroid hormones and RAGE protein were evaluated using ELISA and Western blotting. Data were analyzed using GraphPad Prism software (ver. 9), and P<0.05 was considered significant. Our findings showed that HGA treatment significantly (P=0.0001) increased RAGE (by 140.66%), STAR (by 117.65%), 3β-HSD (by 165.68%), and 17β-HSD (by 122.15%) expression, while it decreased CYP19A1 (by 68.37%) expression. RAGE protein level (by 267.10%) was also increased in HGA-treated GCs. A significant decrease in estradiol (by 59.66%) and a slight and sharp elevation in progesterone (by 30.40%) and total testosterone (by 158.24%) levels was also observed. ALA treatment ameliorated the HGA-induced changes in steroidogenic enzyme mRNA levels (P=0.001) and steroid hormone secretion (P=0.010). This work shows that ALA therapy likely corrects hormonal dysfunctions caused by AGEs in luteinized GCs. This effect is probably achieved by decreased RAGE expression. Clinical research is needed to understand how AGEs and ALA interact in the ovary, which might lead to a more targeted ovarian dysfunction therapy.

Hepatoprotective potential of alpha-lipoic acid against gliclazide-induced liver injury in high-glucose-exposed human liver cells and experimental type 2 diabetic rats

Growing clinical evidence shows that sulfonylurea therapy for patients with type 2 diabetic mellitus (T2DM) contributes to progressive worsening of their liver. The present study presents hepatotoxicity induced by gliclazide, a second-generation sulfonylurea, and alpha-lipoic acid (ALA) as a novel and promising drug for T2DM treatment. Normal human liver cells (HL-7702) were incubated with high-glucose DMEM in the presence or absence of gliclazide and ALA for 72 h, and cell viability and death were measured by flow cytometry. Next, Sprague-Dawley rats were subjected to 12 h of fasting, and fasting blood glucose was measured. The rats were randomized into four groups: HC (healthy control; n = 7), T2DM (diabetic rats without treatment; n = 9), GLC (diabetic rats with 15 mg/kg gliclazide treatment; n = 7) and GLC+ALA (diabetic rats with gliclazide and 60 mg/kg ALA treatment; n = 7). T2DM was induced by a bolus administration of 110 mg/kg nicotinamide and 55 mg/kg streptozotocin intraperitoneally. The experimental protocol lasted for 6 weeks after which the animals were sacrificed and pancreas, liver and blood samples were collected for biochemical, histological and molecular analyses. Compared to healthy control (HC) group, exposure of HL-7702 cells to high glucose induced significant cell death by 19 % (p < 0.001), which was exacerbated with gliclazide treatment by 29 % (p < 0.0001) but markedly reduced by 6 % to near HC value following ALA treatment. In vivo, GLC-treated rats had severe liver damage characterized by increased hepatocellular vacuolation, and significant expression of ED-1, iNOS and caspase-3 as well as markedly high levels of liver enzymes (aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase compared to T2DM rats. Interestingly, ALA administration prevented these pathological changes and protected the diabetic liver to levels comparable to HC rats. ALA showed hepatoprotective effect against gliclazide-induced hepatotoxicity by suppressing inflammation and apoptosis while activating antioxidant pathway in the diabetic liver.Abbreviations: ALA, Alpha-lipoic acid; ALT, Alanine aminotransferase; ALP, Alkaline phosphatase; AMPK, Adenosine monophosphate-activated protein kinase; AST, Aspartate aminotransferase; ATP, Adenosine triphosphate; DMEM, Dulbecco’s Modified Eagle Medium; EDTA, ethylenediaminetetraacetic acid; FBG, Fasting blood glucose; FBS, Fetal bovine serum; GLC, Gliclazide; GLUT4, Glucose transporter type 4; GSH, Glutathione; H&E, Hematoxylin/Eosin; HbA1c, Glycosylated haemoglobin A1c; HC, Healthy control; HG, Hyperglycemic group; HOMA-β, Homeostasis model assessment of β-cell function; IL-1β, Interleukin-1β; IL-6, Interleukin-6; iNOS, Inducible nitric oxide synthase; KATP, ATP-dependent potassium channels; MDA, Malondialdehyde; MPTP, Mitochondrial permeability transition pore; NO, Nitric oxide; P/S, Penicillin/streptomycin; PAS, Periodic acid-Schiff; RIA, Radioimmunoassay; ROS, Reactive oxygen species; SOD, Superoxide dismutase; T2DM, Type 2 diabetes mellitus; TBARS, Thiobarbituric acid reactive substances; TNF-α, Tumor necrosis factor-alpha.

Potential effects of Resatorvid and alpha lipoic acid on gentamicin-induced nephrotoxicity in rats.

Gentamicin is an aminoglycoside antibiotic with a rapid bactericidal effect on the treatment of many infections. However, its use at high concentrations for more than 7 days causes nephrotoxic side effects. This study investigated the potential of Resatorvid and alpha lipoic acid (ALA) in mitigating gentamicin-induced nephrotoxicity in rats, considering biochemical, histopathological, and molecular parameters. This study randomly distributed 34 Wistar albino rats into four groups: healthy control (n = 6), Gentamicin (80 mg/kg, n = 7), Gentamicin + Sham (%10 hydroalcoholic solution, n = 7), Gentamicin + Resatorvid (5 mg/kg, n = 7), and Gentamicin + ALA (100 mg/kg, n = 7). Resatorvid treatment led to a statistically significant decrease in urinary IL-18, KIM-1, and NGAL levels, whereas ALA treatment significantly reduced KIM-1 levels compared to the gentamicin-only group. Both Resatorvid and ALA showed partial reductions in urine creatinine levels. Moreover, treatments with Resatorvid and ALA resulted in statistically significant decreases in NRF-2, CAS-3, and NR4A2 expressions. However, only Resatorvid demonstrated a statistically significant decrease in NF-B expression. These findings highlight the potential of Resatorvid in ameliorating gentamicin-induced nephrotoxicity, thereby expanding the therapeutic utility of gentamicin and enhancing its efficacy against infections.

Alpha-lipoic acid upregulates the PPARγ/NRF2/GPX4 signal pathway to inhibit ferroptosis in the pathogenesis of unexplained recurrent pregnancy loss.

With unknown etiology and limited treatment options, unexplained recurrent pregnancy loss (URPL) remains a thorny problem. Ferroptosis, a newly identified type of cell death, has been shown to be crucial in the development in reproductive disorders. This study aims to explore the specific mechanism of ferroptosis in URPL and to uncover whether alpha-lipoic acid (ALA) can inhibit ferroptosis, and then exert a protective effect in URPL. The decidua tissues of URPL and control patients who actively terminated pregnancy were collected. The CBA/J × DBA/2 murine models of URPL were established, and were randomly treated with peroxisome proliferator activated receptor γ (PPARγ) agonists (Rosiglitazone) and ALA. The CBA/J × BALB/c murine models of normal pregnancy were intraperitoneally injected with PPARγ inhibitors (T0070907). Here, we used reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH)/GSSG, and FeRhoNox-1 analysis to detect the level of ferroptosis. We used quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis to evaluate the mRNA level of PPARγ. Besides, western blot and immunofluorescence were utilized to test the expression profile of PPARγ/nuclear factor erythroid 2-related factor 2 (NRF2)/glutathione peroxidase 4 (GPX4). In this study, we found that iron deposition was increased in the decidual tissue of patients with URPL. Additionally, the changes in cell morphology, the level of ROS, MDA, GSH, and the expression of ferroptosis marker proteins NRF2/GPX4 confirmed activated ferroptosis in URPL. Besides, bioinformatics analysis combined with experiments confirmed that PPARγ was critical in triggering NRF2/GPX4 pathway in URPL. Furthermore, URPL mouse models were established, and the results showed that PPARγ/NRF2/GPX4-mediated ferroptosis was also significantly increased, which could be mitigated by ALA treatment. Overall, these findings suggest that ferroptosis may play an important role in URPL, and ALA might be a promising therapeutic drug for improving pregnancy outcomes in URPL via targeting the PPARγ/NRF2/GPX4 pathway.

Alpha lipoic acid mitigates adverse impacts of drought stress on growth and yield of mungbean: photosynthetic pigments, and antioxidative defense mechanism.

Exogenous use of potential organic compounds through different modes is a promising strategy for the induction of water stress tolerance in crop plants for better yield. The present study aimed to explore the potential role of alpha-lipoic acid (ALA) in inducing water stress tolerance in mungbean lines when applied exogenously through various modes. The experiment was conducted in a field with a split-plot arrangement, having three replicates for each treatment. Two irrigation regimes, including normal and reduced irrigation, were applied. The plants allocated to reduced irrigation were watered only at the reproductive stage. Three levels of ALA (0, 0.1, 0.15 mM) were applied through different modes (seed priming, foliar or priming+foliar). ALA treatment through different modes manifested higher growth under reduced irrigation (water stress) and normal irrigation. Compared to the other two modes, the application of ALA as seed priming was found more effective in ameliorating the adverse impacts of water stress on growth and yield associated with their better content of leaf photosynthetic pigments, maintenance of plant water relations, levels of non-enzymatic antioxidants, improved activities of enzymatic antioxidants, and decreased lipid peroxidation and H2O2 levels. The maximum increase in shoot fresh weight (29% and 28%), shoot dry weight (27% and 24%), 100-grain weight (24% and 23%) and total grain yield (20% and 21%) in water-stressed mungbean plants of line 16003 and 16004, respectively, was recorded due to ALA seed priming than other modes of applications. Conclusively, 0.1 and 0.15 mM levels of ALA as seed priming were found to reduce the adverse impact of water stress on mungbean yield that was associated with improved physio-biochemical mechanisms. The findings of the study will be helpful for the agriculturalists working in arid and semi-arid regions to obtain a better yield of mungbean that will be helpful to fulfill the food demand in those areas to some extent.

Alpha-lipoic acid reduces nociception by reducing oxidative stress and neuroinflammation in a model of complex regional pain syndrome type I in mice

Complex regional pain syndrome type I (CRPS-I) is a disabling pain condition without adequate treatment. Chronic post-ischemia pain injury (CPIP) is a model of CRPS-I that causes allodynia, spontaneous pain, inflammation, vascular injury, and oxidative stress formation. Antioxidants, such as alpha lipoic acid (ALA), have shown a therapeutic potential for CRPS-I pain control. Thus, we aim to evaluate if ALA repeated treatment modulates neuroinflammation in a model of CRPS-I in mice. We used male C57BL/6 mice to induce the CPIP model (O-ring torniquet for 2 h in the hindlimb). For the treatment with ALA or vehicle (Veh) mice were randomly separated in four groups and received 100 mg/kg orally once daily for 15 days (CPIP-ALA, CPIP-Veh, Control-ALA, and Control-Veh). We evaluated different behavioral tests including von Frey (mechanical stimulus), acetone (cold thermal stimulus), rotarod, open field, hind paw edema determination, and nest-building (spontaneous pain behavior). Also, hydrogen peroxide (H2O2) levels, NADPH oxidase and superoxide dismutase (SOD) activity in the sciatic nerve and spinal cord, and Iba1, Nrf2, and Gfap in spinal cord were evaluated at 16 days after CPIP or sham induction. Repeated ALA treatment reduced CPIP-induced mechanical and cold allodynia and restored nest-building capacity without causing locomotor or body weight alteration. ALA treatment reduced SOD and NADPH oxidase activity, and H2O2 production in the spinal cord and sciatic nerve. CPIP-induced neuroinflammation in the spinal cord was associated with astrocyte activation and elevated Nfr2, which were reduced by ALA. ALA repeated treatment prevents nociception by reducing oxidative stress and neuroinflammation in a model of CRPS-I in mice.

Effects of Oral Alpha-Lipoic Acid Treatment on Diabetic Polyneuropathy: A Meta-Analysis and Systematic Review.

Alpha-lipoic acid (ALA) was found to improve the symptoms in patients with diabetic sensorimotor peripheral neuropathy (DSPN) by reducing oxidative stress and ameliorating microcirculation. Our meta-analysis is aimed at evaluating the effects of oral-administered ALA versus a placebo in patients with DSPN and determining the optimal dosage for this treatment. We systematically reviewed randomized controlled trials (RCTs) in the PubMed, Embase, and Cochrane databases to determine the efficacy of oral ALA for patients with DSPN. The primary outcome was total symptoms' score (TSS), and secondary outcomes were the neurological disability score (NDS), neuropathy impaired score (NIS), NIS-lower limb (NIS-LL), vibration perception threshold (VPT), nerve conduction study (NCS) results, and global satisfaction. A subgroup analysis of the ALA dosage (600, 1200, and 1800 mg/day) was also conducted. Ten RCTs (1242 patients) were included. ALA treatment produced favorable results for TSS (a dose-related trend was observed), NDS, and the global satisfaction score. For VAS, VPT, NIS-LL, and NCS results, ALA did not produce favorable results. ALA treatment had favorable effects on DSPN by reducing sensory symptoms, and it resulted in a dose-dependent response relative to the placebo for TSS and the global satisfaction score. The use of ALA to prevent neurological symptoms should be further researched.

Alpha Lipoic Acid (ALA) Alleviates Hepatocytes Toxicity of Titanium Dioxide Nanoparticles in Rats

BACKGROUND: Titanium dioxide nanoparticles (TiO2 NPs) uptake may primarily cause adverse effects by inducing oxidative stress, resulting in cell damage, genotoxicity, inflammation, and immune response. To date, there are limited studies investigating the adverse effect of TiO2 NPs on liver health and no studies found a naturally occurring compound able to ameliorate such effect. Thus, this study investigated alpha lipoic acid (ALA) potential for reversing the biochemical and histopathological changes that TiO2 NPs exposure causes in rat liver.METHODS: Thirty adult male albino rats were divided into: control rats received distilled water, control rats treated with 50 mg/kg ALA, rats intoxicated with TiO2 NPs, and TiO2 NPs-intoxicated rats treated 50 mg/kg ALA. Rats were sacrificed before blood samples were collected to assess the liver function using parameters of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, albumin and total protein. Liver tissue homogenates were prepared to assess hepatic antioxidant and oxidative stress using parameters of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and malondialdehyde (MDA). Liver tissue sections were used for histopathological analysis and caspase-3 immunohistochemical analysis.RESULTS: TiO2 NPs produced deleterious effects on rat liver tissue, as confirmed through biochemical results, caspase-3 immunohistochemistry, and histological alterations. TiO2 NPs intoxication induced hepatocyte vacuolation, blood vessels congestion, biliary proliferation, apoptosis, and fibrosis. However, ALA treatment of TiO2 NPs-intoxicated rats significantly alleviated deleterious impact on the liver.CONCLUSION: Administration of 600 mg/kg TiO2 NPs to rats resulted in hepatic degenerative lesions, depletion of GSH, oxidative stress, and apoptosis. However, these changes were mitigated by ALA administration. Therefore, ALA offers protection against deleterious effects of TiO2 NPs intoxication.KEYWORDS: titanium dioxide nanoparticles, TiO2 NPs, hepatotoxicity, alpha-lipoic acid (ALA), rat

Alpha-lipoic acid modulates the diabetes mellitus-mediated neuropathic pain via inhibition of the TRPV1 channel, apoptosis, and oxidative stress in rats.

Diabetes mellitus (DM) is a chronic syndrome involving neuropathic pain. Increased oxidative stress in DM is assumed to increase free reactive oxygen radicals (ROS) and causes diabetic damage. The sciatic nerve (ScN) and dorsal root ganglion (DRG) both contain high levels of the TRPV1 channel, which is triggered by capsaicin and ROSs and results in increased Ca2+ entry into the neurons. Alpha-lipoic acid (ALA) is considered an important part of the antioxidant system. To better characterize the protective effects of ALA on the DM-induced neuronal through TRPV1 modulation, we investigated the role of ALA on DM-induced neuropathic pain, oxidative ScN, and DRG damage in diabetic rats. Forty adult Wistar albino female rats were divided into four groups as control, ALA (50mg/kg for 14 days), streptozotocin (STZ and 45mg/kg and single dose), and STZ + ALA. Rats were used for the pain tests. After obtaining the DRGs and ScN, they were used for plate reader, patch-clamp, and laser confocal microscope analyses. We observed the modulator role of ALA on the thresholds of mechanical withdrawal pain (von Frey test) and hot sensitivity pain (hot plate test) in the STZ + ALA group. The treatment of ALA decreased STZ-induced increase of TRPV1 current densities, intracellular free Ca2+ concentrations (Fura-2 and Fluo - 3/AM), ROS, caspase 3, caspase 9, mitochondrial membrane potential, and apoptosis values in the ScN and DRG neurons, although its treatment induced the increase of cell viability and body weight gain. The treatment of ALA acted a neuroprotective role on the TRPV1 channel stimulation-mediated Ca2+ influx, neuropathic pain, and neuronal damage in diabetic rats. The neuroprotective role of ALA treatment can be explained by its modulating the TRPV1 channel activity, intracellular Ca2+ increase-induced oxidative stress, and apoptosis.

Alpha-Lipoic Acid Ameliorates Doxorubicin-Induced Cognitive Impairments by Modulating Neuroinflammation and Oxidative Stress via NRF-2/HO-1 Signaling Pathway in the Rat Hippocampus.

Chemotherapy-induced cognitive impairment (CICI) is a common complication associated with the use of chemotherapeutics. Doxorubicin (DOX) is a reactive oxygen species (ROS) producing anticancer agent capable of causing potential neurotoxic effects via cytokine-induced oxidative and nitrosative damage to brain tissues. On the other hand, alpha-lipoic acid (ALA), a nutritional supplement, is reputable for its excellent antioxidant, anti-inflammatory, and anti-apoptotic activities. Consequently, the objective of the current investigation was to examine any potential neuroprotective and memory-improving benefits of ALA against DOX-induced behavioral and neurological anomalies. DOX (2mg/kg/week, i.p.) was administrated for 4weeks to Sprague-Dawley rats. ALA (50, 100, and 200mg/kg) was administered for 4weeks. The Morris water maze (MWM) and novel objective recognition task (NORT) tests were used to assess memory function. Biochemical assays with UV-visible spectrophotometry were used to analyze oxidativestress markers [malondialdehyde (MDA), protein carbonylation (PCO)], endogenous antioxidants [reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)] and acetylcholinesterase (AChE) activity in hippocampal tissue. Inflammatory markers [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nuclear factor kappa B (NF-κB)], nuclear factor erythroid 2-related factor-2 (NRF-2) and hemeoxygenase-1 (HO-1) levels were estimated using enzyme-linked immunosorbent assay (ELISA). In addition, reactive oxygen species (ROS) levels were measured in hippocampus tissue using 2-7-dichlorofluorescein-diacetate (DCFH-DA) assay with fluorimetry. ALA treatment significantly protected against DOX-induced memory impairment. Furthermore, ALA restored hippocampal antioxidants, halted DOX-induced oxidative and inflammatory insults via upregulation of NRF-2/HO-1 levels, and alleviated the increase in NF-κB expression. These results indicate that ALA offers neuroprotection against DOX-induced cognitive impairment, which could be attributed to its antioxidant potential via the NRF-2/HO-1 signaling pathway.

Alpha lipoic acid treatment in late middle age improves cognitive function: Proteomic analysis of the protective mechanisms in the hippocampus

Alpha lipoic acid (ALA), a powerful antioxidant, has the potential to relieve age-related cognitive impairment and neurodegenerative disease. Clinical randomized controlled studies have demonstrated the cognitive improvement effects of lipoic acid in Alzheimer's disease (AD). In the present study, we examined the effects of ALA on cognitive function in ageing mice and its protective mechanisms. Eighteen-month-old male C57BL6/J mice received ALA or normal saline for 2 months. The Morris water maze test revealed improved cognitive function in animals that received ALA. Furthermore, tandem Mass Tags (TMT) based liquid chromotography with mass spectrometry/mass spectrometry (LC-MS/MS) was established to identify the target proteins. The results showed that 10 proteins were changed significantly. Gene Ontology (GO) analysis indicated that the upregulated proteins were enriched in terminal bouton, synaptic transmission and lipid transporter activity while the down-regulated proteins were involved in nuclear transcription factor-κB binding, apoptosis and mitogen-activated protein kinase binding. Based on the GO results, two upregulated proteins oxysterol-binding protein-related protein 10 (OSBPL10) and oligophrenin 1 (OPHN1), and one downregulated protein, CDK5 regulatory subunit-associated protein 3 (CDK5rap3), were validated through Western blotting. The results were consistent with the proteomic results. Modulation of synaptic transmission, lipid transporter activity and neuroinflammation appears to be the mechanisms of ALA in the aged brain.

Effects of alpha lipoic acid treatment during in vitro maturation on the development of porcine somatic cell nuclear transfer embryos.

Oxidative stress influences the embryo production efficiency in vitro. We investigated the effects of alpha lipoic acid (ALA) treatment during the in vitro maturation (IVM) period on the porcine somatic cell nuclear transfer (SCNT) embryo production. After IVM, maturation rates of the 12.5- and 25-μM ALA-treated groups were not significantly different from those of the 0-μM ALA-treated group. Compared to those in the 0-μM ALA-treated group, the reactive oxygen species and glutathione levels were significantly decreased and increased, respectively, in the cytoplasm of matured oocytes in the 12.5-50-μM ALA-treated groups. Apoptosis rate in cumulus cells after IVM was significantly lower in the 12.5-50-μM ALA-treated groups than in the 0-μM ALA-treated group. Blastocyst formation rate was significantly higher in parthenogenetic oocytes treated with 12.5-μM ALA than in the 0-, 25-, and 50-μM ALA-treated groups. Similarly, in SCNT embryos, the 12.5-μM ALA-treated group showed a significantly higher blastocyst formation rate than the 0-μM ALA-treated group. Apoptosis rate in SCNT blastocysts was significantly decreased by 12.5-μM ALA treatment. The results showed that treatment with 12.5-μM ALA during IVM improves porcine SCNT embryo development and partial quality.

Efficacy of intravenous alpha lipoic acid in the treatment of neuropatic pain due to carpal tunnel syndrome.

<p>In this study, we analyzed the effect of oral and oral + intravenous Alpha-lipoic acid (ALA) treatment on pain level and physical examination findings in patients diagnosed with carpal tunnel syndrome (CTS).</p>. <p>A total of 115 patients patricipa&shy;ted in the study. Physiotherapy and wrist splint were first applied to all patients diag&shy;nosed with CTS in the study. 40 patients were treated with oral ALA after iv. ALA the&shy;rapy, 35 patients received only oral ALA treatment and 40 patients did not receive any medication. The patients were divided into 3 groups as those who received only splint treatment and physiotherapy, those who received oral ALA treatment, and those who received oral ALA treatment after iv. treat&shy;ment. All patients were assessed be&shy;fore the treatment, and at the 1st and 3rd months of the treatment. In clinical assessment, visual analog scale (VAS) forms were filled to define the pain severity, the Boston symptom severity scale (BSSS) and Boston functional status scale (BFDS) were filled for evaluating symptoms and functional status.&nbsp;</p>. <p>VAS, BSSS and BFDS scores of the patients who were treated with intravenous and then oral ALA were found to be significantly lower at the end of both the 1st and 3rd months compared to the patients who received only oral ALA or no medication (p=0.001; p&lt;0.001), (p=0.001; p&lt;0.001), (p=0.006; p&lt;0.001).</p>. <p>We think that iv. ALA is effective in the treatment of symptoms associated with CTS.</p> <p>&nbsp;</p>.

Abstract 11586: Therapeutic Potential of Alpha Lipoic Acid in a Rat Model of Superimposed Preeclampsia: Effect on Maternal Signs, Placental Development and Fetal Growth

Introduction: Superimposed preeclampsia (SPE) occurs in 25-40% of pregnant women affected by chronic hypertension and is associated with adverse maternal and neonatal outcomes. In previous studies, we have demonstrated that pregnant Stroke-prone Spontaneously Hypertensive Rat represent a spontaneous SPE model, characterized by defective trophoblast invasion and placental oxidative stress, asymmetric fetal growth restriction and worsening maternal hypertension with renal dysfunction towards term. Here, we sought to evaluate the therapeutic potential of alpha lipoic acid (ALA), a potent antioxidant, during early pregnancy in this model. Methods: Congenic timed breedings were established using SHRSP and Wistar Kyoto (WKY) females (10-12 weeks old, 200-250 g body weight, N = 10 animals/day analyzed). Upon vaginal plug detection (gestation day (GD)1), dams were assigned to two groups: ALA treatment, injected 25mg/kg body weight ALA i.p. on GD1, GD8 and GD12 and controls, receiving saline following the same protocol. Systolic blood pressure (SBP) profiles throughout pregnancy were recorded using a noninvasive volume pressure recording device. On GD20, animals were euthanized and fetoplacental specimens isolated for morphological and molecular analyzes. Statistical analysis was run on GraphPad Prism v 8.0, using 2 way ANOVA. Statistical significance was set at p˂ 0.05. Results: Treatment with ALA prevented the pregnancy-dependent SBP increase typical of the SHRSP model (SBP GD14 SHRSP: 169.3±2.1 mmHg vs. SHRSP+ALA: 146.1±3.4, p˂0.001). Furthermore, fetuses carried by ALA-treated SHRSP displayed increased weights (SHRSP: 1.75±0.05g vs. SHRSP+ALA: 1.99±0.01g, p˂0.05) and decreased cephalization indexes on GD20, indicating an improvement in the asymmetric growth restriction pattern. Treated dams also presented increased numbers of glycogen trophoblasts (PAS + cells) in the junctional zone and an enhanced vessel density on Isolectin B4 + staining, suggesting an improved placental function. Conclusions: ALA administration during early pregnancy in the SHRSP model ameliorated maternal signs and improved placental function and fetal growth, emerging as a novel therapeutic intervention in pregnancies affected by chronic hypertension

Alpha-lipoic acid protects against aortic aneurysm and dissection by improving vascular smooth muscle cell function

Alpha-Lipoic acid (ALA) plays a protective role in a variety of vascular diseases, however, its effect on aortic aneurysm and dissection (AAD) has not been reported. In this study, we found that Alpha-Lipoic Acid treatment significantly improved the AAD and AAA development, which was demonstrated by ameliorated aneurysmal dilation, decreased aortic dissection and aneurysm incidence, improved aortic morphology and inhibited elastin degradation. ALA blunted extra-cellular matrix degradation, vascular smooth muscle cell (VSMC) loss and phenotype transformation. Moreover, the protective effect of ALA on VSMCs may be related to the amelioration of mitochondrial dysfunction. In conclusion, our study revealed that ALA exerts inhibitory effects against progression of AAD, thus suggesting that ALA may be a novel therapeutic molecule for AAD.

The effects of alpha-lipoic acid (ALA) on the urinary bladder injury in rats exposed to chronic stress: A histochemical study

Objective: In the present study, we aimed to investigate the morphological and biochemical effects of alpha-lipoic acid (ALA) on bladder injury caused by water avoidance stress (WAS) and to show its effect on the number of degranulated mast cells, which increase after stress. Materials and Methods: Wistar albino rats were subjected to WAS and the animals in the treatment group were injected ALA. After the urinary bladder tissues were subjected to routine tissue processing, hematoxylin-eosin staining and periodic acid-Schiff reaction were applied to observe general morphology and acidic toluidine blue method to investigate mast cells. Biochemical assessments of malondialdehyde (MDA) and glutathione (GSH) were also obtained. Transmission electron microscope was used for the ultrastructural, and scanning electron microscope for the topographical analyses. Results: The experiments showed that chronic stress caused injury in the bladder, increased degranulated and total number of mast cells and decreased GSH and increased MDA levels. ALA treatment after WAS ameliorated bladder injury in most areas, decreased degranulated and total mast cell number and increased GSH and decreased MDA levels. Conclusion: It was concluded that ALA can be a useful agent in the treatment of interstitial cystitis.

Protective Effects of Alpha-Lipoic Acid against 5-Fluorouracil-Induced Gastrointestinal Mucositis in Rats.

Alpha-lipoic acid (ALA) is extensively utilized in multivitamin formulas and anti-aging products. The purpose of this study was to investigate the potential protective benefits of ALA on 5-fluorouracil (5-FU)-induced gastrointestinal mucositis in Wistar albino rats. Tissues from the stomach, small intestine, and large intestine were excised, and blood sera were obtained to identify biochemical indices such as TNF-α, IL-1β, MDA, GPx, SOD, MMP-1, -2, -8, and TIMP-1. A histopathological study was also performed. The results revealed mucositis-elevated TNF-, IL-1, MDA, MMP-1, -2, -8, and TIMP-1 levels in both tissues and sera, and these values dropped dramatically following ALA treatment. Reduced SOD and GPx activities in mucositis groups were reversed in ALA-treated groups. The damage produced by mucositis in the stomach and small intestine regressed in the ALA-treated group, according to histopathological evaluation. Consequently, the implementation of ALA supplementation in 5-FU therapy may act as a protective intervention for cancer patients with gastrointestinal mucositis. In light of the findings, ALA, a food-derived antioxidant with pleiotropic properties, may be an effective treatment for 5-FU-induced gastrointestinal mucositus, and prevent oxidative stress, inflammation, and tissue damage in cancer patients receiving 5-FU therapy.

A novel approach to alpha-lipoic acid therapy in the treatment of diabetic peripheral neuropathy

Diabetic peripheral neuropathy (DPN) is a heterogenic disorder prevalent amongst patients suffering from diabetes mellitus (DM), with symptoms comprising neuropathic pain, paresthesia, and numbness in distal lower limbs. Alpha-lipoic acid (ALA) is proposed as a pathogenesis-oriented treatment option, targeting underlying causes of neural lesions such as hyperglycemia, metabolic and microvascular dysfunctions, and cellular oxidative stress. We performed a comprehensive review of controlled clinical trials demonstrating the clinical usefulness of ALA in the treatment of DPN, published in the last 5 years to determine the benefits of ALA monotherapy and combined treatments with other known antioxidants. We also investigated the differential efficacy of oral versus intravenous ALA administration. Clinical trials show the efficacy of ALA treatment, attributed to its anti-inflammatory, anti-hyperglycemic, and antioxidant properties, as well as its function in the endothelial activation and lipid metabolism parameters. ALA supplementation is associated with amelioration in nerve conduction velocity scores, clinically significant reduction of reported neuropathic pain, burning and paresthesia, as well as a decrease in serum triglycerides, improved insulin sensitivity, and quality of life.

Redox Active α-Lipoic Acid Differentially Improves Mitochondrial Dysfunction in a Cellular Model of Alzheimer and Its Control Cells.

Introduction: Alpha lipoic acid (ALA) is a sulphur-containing organic compound, derived from octanoic acid, and an important cofactor for mitochondrial respiratory enzymes. It has strong antioxidant properties that improve mitochondrial function. We investigated if ALA improves mitochondrial dysfunction in a cellular model of Alzheimer’s disease (AD). Methods: SH-SY5Y-APP695 cells were used as a model for an early stage of AD. Vector-transfected SH-SY5Y-MOCK cells served as controls. Using these cells, we investigated mitochondrial respiration (OXPHOS), mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) production, and citrate synthase activity (CS) in cells treated with ALA. Cells were treated for 24 h with different concentrations of ALA and with or without the complex I inhibitor rotenone. Results: Incubation with ALA showed a significant increase in ATP levels in both SH-SY5Y-APP695 and SH-SY5Y-MOCK cells. MMP levels were elevated in SH-SY5Y-MOCK cells, treatment with rotenone showed a reduction in MMP, which could be partly alleviated after incubation with ALA in SH-SY5Y-MOCK cells. ALA treatment showed significant differences in respiration chain complex activities in SH-SY5Y-MOCK cells. Citrate synthase activity was unaffected. ROS levels were significantly lower in both cell lines treated with ALA. Conclusions: ALA increased the activity of the different complexes of the respiratory chain, and consequently enhanced the MMP, leading to increased ATP levels indicating improved mitochondrial function. ALA only marginally protects from additional rotenone-induced mitochondrial stress.