Alpha-lipoic Acid Supplementation Research Articles

Effects of Alpha Lipoic Acid Supplementation on Slow Skeletal Muscle Mass and Contractile Functions in Type 2 Diabetic Male Sprague Dawley Rats

Objective: To see the Effects of Alpha-Lipoic Acid (ALA) supplementation on slow skeletal muscle mass andcontractile functions in type 2 diabetic male Sprague Dawley rats.Study Design: Quasi-experimental study.Place and Duration of Study: The study was carried out at the Physiology Research Lab, Army MedicalCollege, Rawalpindi, Pakistan from June 2019 to April 2021 in collaboration with the National Institute of Health(NIH) Islamabad, Pakistan.Methods: Sixty adult SD rats were divided into three equal groups. Rats were fed on a standard diet as per NIHprotocols. After 2 weeks type 2 Diabetes mellitus (T2DM) was induced in groups 2 and 3 by injecting low dose35mg of streptozotocin (STZ) in the abdomen intraperitoneally. T2DM was successfully developed andconfirmed by measuring glucose levels through a glucometer. Group 3 was injected with Alpha Lipoic acid30mg/kg/day at the lower abdomen for the next two weeks. After 04 weeks, soleus muscles were dissected.The animal data acquisition unit (iWorx) was used for assessing the contractile functions of soleus.Results: Alpha Lipoic acid group showed improvement in muscle mass, muscle tension strength, and recoveryfrom fatigue after applying fatigue protocol as compared to group 2.Conclusion: Alpha Lipoic acid supplementation improves contractile force and delays fatigue in the soleusmuscles of diabetic rats. How to cite this: Khan BU, Yousef I, Arshad S, Ikram F, Ali A, Ullah I. Effects of Alpha Lipoic Acid Supplementation on Slow Skeletal Muscle Mass and Contractile Functions in Type 2 Diabetic Male Sprague Dawley Rats. Life and Science. 2024; 5(2): 216-221. doi: http://doi.org/10.37185/LnS.1.1.408

Impact of combined alpha-lipoic acid and mitoquinone supplementation on myocardial infarction in aged rats: Heart performance and molecular mechanisms

BackgroundThis study aimed to investigate the effects of combined alpha-lipoic acid (ALA) and mitoquinone (Mito Q) supplementation on cardiac function and the underlying mechanisms in aged rats with myocardial infarction (MI). MethodsThe aged rats underwent left anterior descending artery (LADA) occlusion for 30 min, followed by reperfusion for 24 h. ALA (100 mg/kg, gavage) and Mito Q (10 mg/kg, IP) were administered daily for two weeks before ischemia. Cardiac function, inflammatory, and apoptotic markers were evaluated 24 h after ischemia. ResultsThe results of this study indicated that the administration of the combination of ALA and Mito Q significantly improved cardiac function. This improvement was linked to a reduction in the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β (P < 0.001) and apoptotic markers (Bax, caspase-3, and Cyt-c), as well as a decrease in the percentage of TUNEL-positive cells (P < 0.001). ConclusionThe study revealed that combined intervention synergistically mitigated cardiac dysfunction by suppressing inflammatory and apoptotic pathways in aged rats with MI. Further research is needed to validate the potential of ALA and Mito Q as therapeutic options for elderly people at risk of heart attacks.

Effectiveness of Vitamin D and Alpha-Lipoic Acid in COVID-19 Infection: A Literature Review.

Over three years since the World Health Organization (WHO) declared COVID-19 a pandemic, it is still a global burden. Vaccines against COVID-19, caused by SARS-CoV-2, are available and effective for preventing disease. However, their protective effects are not 100%. Currently, the U.S. Food and Drug Administration (FDA) has only approved a limited number of inpatient treatments for COVID-19, such as remdesivir, baricitinib, and tocilizumab. These medications have indications and contraindications applicable to a select patient population. Finding additional effective therapies that are widely available with limited risk could be vital in optimizing treatment strategies for this viral illness. Some vitamins and supplements have been identified as potential options for managing COVID-19. Vitamin D (VD) deficiency has been associated with respiratory tract infections. Moreover, alpha-lipoic acid (ALA) is a powerful antioxidant and helps reduce inflammatory responses in many pathologic conditions. This review aims to analyze the current evidence regarding the effectiveness of VD and alpha-lipoic acid in COVID-19 infection in both outpatient and hospitalized patients. Relevant randomized controlled trials (RCTs) were identified via the PubMed database from January 1, 2021, to December 31, 2023. Inclusion criteria were as follows: the study design was a randomized controlled trial (RCT), the usage of a constant dose during the intervention period without any additional boluses, and a research ethics committee approved it. Exclusion criteria included a lack of an outcome or apparent intervention, additional boluses, or a single-dose regimen in all the interventional groups. There were 11 studies with a total sample size of 35,717 patients that met the criteria for this review. A total of 10 RCTs examined the efficacy of VD, and one RCT that reviewed the efficacy of ALA was identified. All of the articles investigated the use of VD or ALA during the treatment of COVID-19. The endpoints of each study varied, including length of stay in hospital, viral load, SARS-CoV-2 infection rate, mechanical ventilation, inflammatory markers, clinical symptoms, Sequential Organ Failure Assessment (SOFA) score, and mortality. In 8/10 VD supplementation trials, significant differences were identified between the interventional and placebo groups in the aforementioned parameters. In 2/10 VD supplementation trials, no significant differences were identified. The ALA supplementation RCT found no differences between the interventional and placebo groups in the SOFA score and 30-day all-cause mortality rate. The current literature suggests that VD can potentially reduce the SARS-CoV-2 infection rate, oxygen requirements, inflammatory markers, clinical symptoms, and mortality. Regarding ALA, although there was a suggestion of benefit, it was not statistically significant. Common limitations among the different studies included relatively small sample sizes, different geographical patient locations among studies, and differences in dosages. Trials investigating the effects of higher doses of VD supplementation on SARS-CoV-2 infection should be conducted. More research is needed to define best practices and optimal dosing protocols for the use of VD in COVID-19.

The effect of Chromium Propionate and Alpha-Lipoic Acid Supplementation on Gene Expression of Cytokine Profile in the Spleen Tissue of Broilers

The effect of Chromium Propionate and Alpha-Lipoic Acid Supplementation on Gene Expression of Cytokine Profile in the Spleen Tissue of Broilers

Assessing the clinical and biochemical efficacy of alpha-lipoic acid in patients with non-alcoholic fatty liver disease: A randomized placebo-controlled clinical trial

Given the importance of inflammatory and metabolic markers in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), this study was designed to evaluate the effects of alpha-lipoic acid (ALA) supplementation on inflammatory and serum levels of fetuin-A, sirtuin1 (SIRT-1), cytokeratin 18 (CK-18), and hepatic steatosis in patients with NAFLD. In a double-blind, placebo-controlled, randomized clinical trial, 50 patients with NAFLD were randomized to receive daily supplementation with either two capsules of ALA (each capsule containing 600 mg ALA plus 400 mg/day of vitamin E) or two placebo capsules (two placebo capsules plus 400 mg/day of vitamin E) for 12 weeks. Significant reductions in homeostasis model assessment for insulin resistance (HOMA-IR) score and serum levels of insulin and fetuin-A were observed in the ALA group compared to the placebo group (all P < 0.05). ALA supplementation was significantly more effective than placebo in reducing hepatic steatosis by at least one grade.

Effects of alpha lipoic acid supplementation on post-thaw quality of drone semen

This study aimed to determine the effect of alpha-lipoic acid (ALA) on post-thaw quality of bee semen. In the study, semen from sexually mature drone were collected. A series of experiments were carried out in which the retrieved semen was diluted with diluents containing different ALA concentrations or without ALA supplement (control). Cryopreserved sperm were thawed, and evaluated for motility (phase-contrast microscope), plasma and acrosomal membrane integrity, mitochondrial membrane potential, and DNA fregmantation. The results obtained showed that the highest motility after thawing was observed in the groups containing ALA 0.25 mmol (P < 0.05). Likewise, plasma membrane integrity was found to be better preserved in the ALA 0.25 mmol-added group than in other groups. Acrosomal integrity were also higher in the ALA-containing groups than in the control group (P < 0.05). The results of this study show that ALA supplementation especially at 0.25 mmol improved post-thawed sperm motility, plasma membrane functionality, and mitochondrial membrane potantial quality of honeybee semen.

The Effects of Alpha Lipoic Acid on Oxidative Stress, Lipid Profile, and Blood Glucose Levels in Type 2 Diabetic Male Sprague Dawley Rats

Objective: To determine the effect of Alpha Lipoic Acid (ALA) on blood glucose, lipid profile, and oxidative stress in streptozotocin-induced type II diabetic male Sprague Dawley rats.Study Design: Laboratory-based experimental study.Place and Duration of the Study: The study was carried out at the Physiology Research Lab, Army Medical College, Rawalpindi, Pakistan, from 20th January 2021 to 24th June 2021.Methods: Thirty Sprague Dawley (SD) rats were divided into three equal groups. Group I was given a normal standard rat diet. In Groups II and III after feeding a diet rich in fat and calories for 2 weeks, after feeding a diet rich in fat and calories for 2 weeks, a single low dose of streptozotocin was injected for Type 2 Diabetes Mellitus (T2DM) induction. Alpha Lipoic Acid 30 mg/kg body weight/day was administered intraperitoneally in Group III for 01 weeks after the development of T2DM.Results: The blood glucose, lipid profile, and serum Malondialdehyde levels were deranged in the diabetic group. After Alpha Lipoic Acid supplementation, the blood glucose levels, Serum MDA, and levels of triglycerides, cholesterol, and Low Density Lipoproteins decreased, whereas High Density Lipoproteins level were significantly raised (p &lt;0.001) in group III as compared to the diabetic group II. Conclusion: Treatment with Alpha Lipoic Acid reduces oxidative stress and improve reduces oxidative stress and improves glycemic and lipid profiles in T2DM rats.&#x0D; How to cite this: khan BU, Arshad S, Ikram F, Yousef I, Naizi I, Ismaeel M. The Effects of Alpha Lipoic Acid on Oxidative Stress, Lipid Profile and Blood Glucose Levels in Type 2 Diabetic Male Sprague Dawley Rats. Life and Science. 2024; 5(1): 89-94. doi: http://doi.org/10.37185/LnS.1.1.405

Ameliorating the Cardiovascular Disorders after Ovariectomy By Alpha Lipoic Acid Supplementation

Ameliorating the Cardiovascular Disorders after Ovariectomy By Alpha Lipoic Acid Supplementation

Kwas alfa-liponowy w prewencji powikłań cukrzycowych

Diabetes is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Diabetes is due to either the pancreas not producing enough insulin, or the cells of the body not responding properly to the insulin produced (insulin resistance). Chronic hyperglycemia is associated with damage of small and large blood vessels in many tissues and organs (micro- and macroangiopathy). Microvascular complications may contribute to the diabetic retinopathy and neuropathy. Diabetes is strongly associated with increased oxidative stress, which could be a consequence of either increased production of free radicals or reduced antioxidant defenses. Many of the biochemical pathways (e.g., protein glycation, polyol pathway, protein kinase C activation) associated with hyperglycemia can result in increased reactive oxygen species. An ideal therapeutic antioxidant should fulfill several criteria. These include absorption from the diet, conversion in cells and tissues into usable form, a variety of antioxidant actions (including interactions with other antioxidants) in both membrane and aqueous phases, and low toxicity. Alpha-lipoic acid is unique among natural antioxidants in its ability to fulfill all of these requirements. Alpha-lipoic acid has been shown to have diverse beneficial effects suggesting that it acts by multiple mechanisms on oxidative stress parameters. Alpha-lipoic acid’s antioxidant properties consist of the following: 1) its capacity to directly scavenge reactive oxygen species, 2) its ability to regenerate endogenous antioxidants, such as glutathione, vitamins E and C, and 3) its metal chelating activity, resulting in reduced reactive oxygen species production. Alpha-lipoic acid prevents micro-vascular damage through normalized pathways downstream of mitochondrial overproduction of reactive oxygen species. Alpha-lipoic acid inhibits diabetes-induced apoptosis of both endothelial cells and pericytes, signs and predictor of retinopathy, and prevents nerve ischemia and hypoxia whitch could cause neuropathy. Alpha-lipoic acid supplementation is an achievable adjunct therapy to help prevent vision loss and reduce neuropathic symptoms in diabetic patients. Honokiol is a natural polyphenolic compound extracted from the bark, cone and leaves of Magnolia. Honokiol is used in traditional Chinese and Japanese medicine for the treatment of various diseases. This promising bioactive compound presented an wide range of therapeutic and biological activities which include neuroprotective, anti-spasmodic, antidepressant, anti-tumorigenic, antithrombotic, antimicrobial, analgesic properties, and others. Some of its mechanism for exhibiting its pharmacological effects includes inhibition of oxidative stress and suppression of pro-inflammatory cytokines (TNF-α, IL-10 and IL-6). Honokiol might exert its protective effect on hyperglycemia-induced cell damage in human endothelial cells through the inhibition of NF-κB and COX-2 upregulation. Low-dose of honokiol may have the potential to protect endothelial cells from damage associated with elevated glucose.

Dietary alpha-lipoic acid boosts growth, immune-antioxidant traits, behavior, and transcriptomes of antioxidant, apoptosis, and immune-related genes to combat cold stress in Nile tilapia (Oreochromis niloticus)

AbstractWater temperature is a major environmental factor affecting fish activity, physiology, behavior, and growth. Alpha lipoic acid (ALA) has garnered much attention lately as an aqua feed supplement because of its antioxidant effects. Thus, this study aimed to assess the effect of dietary ALA on performance, hematological and immunological indices, behavior and oxidative stress, apoptosis, and genetic inflammation in Oreochromis niloticus following 60 days of cold stress. Two hundred forty fish were divided into four groups (15 fish/replicate, N = 60 fish/group). The control (CNT) and ALA groups were reared at 25 °C and fed a basal diet without any supplementation or a basal diet containing 600 mg ALA/kg diet, respectively. The cold water-stressed group (CWS) and ALA + CWS groups were reared at 18 °C and fed basal and basal diets containing ALA, respectively. The results revealed that dietary ALA supplementation significantly improved feed utilization and growth in fish. ALA also mitigated CWS-induced microcytic hypochromic anemia and hyperlipidemia. Moreover, ALA supplementation considerably enhanced the antioxidant status and boosted intestinal α amylase, lipase, protease, and serum acetylcholinesterase activity of CWS-exposed fish. Besides, ALA supplementation significantly reversed CWS-induced upregulation of proinflammatory genes, pro-apoptotic genes, heat shock protein, and proliferating cell nuclear antigen or downregulation of superoxide dismutase and catalase gene expressions in liver and spleen tissues. Furthermore, ALA supplementation reduced CWS-induced histopathological alterations in fish liver, spleen, and intestine. We can conclude that ALA (600 mg/kg diet) could be recommended as an aqua feed supplement to boost growth, antioxidant capacity, and immunity and attenuate inflammatory and apoptotic reactions of fish reared under CWS-induced.

The effect of alpha-lipoic acid supplementation on anthropometric, glycemic, lipid, oxidative stress, and hormonal parameters in individuals with polycystic ovary syndrome: a systematic review and meta-analysis of randomized clinical trials.

This systematic review and meta-analysis aimed to examine the effect of the antioxidant alpha-lipoic acid (ALA) on various cardiometabolic risk factors and hormonal parameters in patients with polycystic ovary syndrome (PCOS). We searched PubMed, EMBASE, SCOPUS, Cochrane Library, and Web of Science databases without language restrictions until May 2023 to find randomized controlled trials (RCTs) that assessed the impact of ALA supplementation on anthropometric, glycemic, lipid, oxidative stress, and hormonal parameters in women with PCOS. Outcomes were summarized using the standardized mean difference (SMD) and 95% confidence interval (CI) in a random-effects model. An I2 statistic of >60% established significant between-study heterogeneity. The overall certainty of the evidence for each outcome was determined using the grading of recommendations, assessment, development, and evaluations system. Seven RCTs met the inclusion criteria. The ALA group had significant reductions in fasting blood sugar (fasting blood sugar (FBS), n=7 RCTs, SMD, -0.60; 95% CI, -1.10 to -0.10; I2=63.54%, moderate certainty of evidence) and homeostatic model assessment for insulin resistance (homeostatic model assessment of insulin resistance (HOMA-IR), n=4 RCTs, SMD, -2.03; 95% CI, -3.85 to -0.20; I2=96.32%, low certainty of evidence) compared with the control group. However, significant differences were observed between the groups in body mass index, insulin, estrogen, follicle-stimulating hormone, luteinizing hormone, testosterone, low-density lipoprotein, highdensity lipoprotein, triglyceride, total cholesterol, malondialdehyde, or total antioxidant capacity profiles. ALA supplementation improves FBS and HOMA-IR levels in women with PCOS. ALA consumption is an effective complementary therapy for the management of women with PCOS.

Effect of Alpha Lipoic Acid (ALA) Supplementation in Goat Oocyte In Vitro Maturation Media on Superoxide Dismutase (SOD) and 8-Hydroxy-2'-Deoxyguanosine (8-OHdG) Levels

Introduction: This study explains about the effect of Alpha Lipoic Acid (ALA) supplementation in goat oocyte In Vitro maturation media on Superoxide Dismutase (SOD) levels and 8-Hydroxy-2'-Deoxyguanosine (8-OHdG) levels with the aim of determining the status of balanced intracellular redox status and good oocyte quality. Objective: This laboratory experimental study contained three treatment groups: no ALA (P0), 25 μmol/L ALA supplementation (P1), and 50 μmol/L ALA supplementation (P2). SOD and 8-OHdG levels were measured using the ELISA method. SOD levels in group P0 were 1.41±0.40 pg/mL, group P1 were 2.04±0.50 pg/mL, and group P2 were 3.65±1.20 pg/mL. Data on 8-OHdG levels in the P0 group was 51.17±27.58 pg/mL, the P1 group was 11.21±5.98 pg/mL, and the P2 group was 12.66±6.01 pg/mL. Results: The P1 group could not significantly increase the SOD level of the P0 group (p&gt;0.05), while the P2 group could significantly increase the SOD level of the P0 group (p&lt;0.05). Data on 8-OHdG levels in the P1 and P2 groups decreased significantly when compared to the P0 group (p&lt;0.05). Conclusion: ALA supplementation at a dose of 50 µmol/L in goat oocyte In Vitro maturation media can increase SOD levels and reduce 8-OHdG levels.

Maternal supplementation of alpha-lipoic acid ameliorates prenatal cytarabine-induced mutilation in reproductive development and function in F1 male adult rats.

Cytarabine (CYT), a prevalent anticancer drug for blood cancers, detrimentally affects male reproductive development and function. Alpha-lipoic acid (ALA), a universal antioxidant, offers defense against chemical-induced reproductive dysfunction. Our study sought to explore ALA's protective role against prenatal CYT-induced reproductive impairment in F1 male adult rats. Pregnant rats were divided into 5 groups and administered normal saline, ALA 200mg/kg, CYT 12.5mg/kg, CYT 25mg/kg, and CYT 25mg/kg + ALA 200mg/ kg from gestational day 8 to 21. On postnatal day 73, F1 male rats were sacrificed, and general, oxidative, steroidogenic, spermatogenic, histological, and morphometrical parameters were evaluated. Prenatal CYT caused dose-dependent reductions in body weight, testis, and accessory gland weights; elevated oxidative stress; delayed puberty onset; sperm anomalies (decreased count, motility, viability, seminal fructose; increased morphological anomalies); impeded steroidogenesis (lower testosterone, follicle-stimulating hormone, luteinizing hormone, 3β-Hydroxysteroid dehydrogenase(HSD), 17β-HSD, and elevated cholesterol); and testicular histopathological and morphometric disturbances. Maternal supplementation of ALA was found to alleviate all the CYT-induced reproductive disruptions. The present work accentuates the beneficial actions of ALA against CYT-induced impairment in reproductive development and functions by combating disruptions in oxidative balance, steroidogenesis, spermatogenesis, and testicular histological aberrations. However, future experimental and clinical studies are warranted to explore the molecular mechanisms involved in the ALA's protection against prenatal CYT-induced testicular injury.

The effects of alpha lipoic acid (ALA) supplementation on blood pressure in adults: a GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials.

There have been various clinical studies on the effect of Alpha lipoic acid (ALA) supplementation on blood pressure (BP), but the findings from these are contradictory. Therefore, we performed a systematic review and dose-response meta-analysis to summarize the relation of ALA supplementation and systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults. A comprehensive search was conducted in Medline (PubMed), Embase, Scopus, and ProQuest up to July 2023. Randomized controlled trials (RCTs) evaluating the effect of ALA on SBP and DBP were included. The pooled weighted mean difference (WMD) of included trials was estimated using a random-effects model. The dose-dependent effect was also assessed. A total of 11 RCTs with the participation of 674 patients were included. The result of the meta-analysis indicated that using ALA supplementation significantly reduced the SBP (WMD = -5.46 mmHg; 95% CI: -9.27, -1.65; p < 0.001) and DBP (WMD = -3.36 mmHg, 95% CI: -4.99, -1.74; p < 0.001). The ALA administrations significantly reduced SBP and DBP at the dosages of <800 mg/day, when administered for ≤12 weeks. The present meta-analysis revealed that ALA supplementation could exert favorable effects on SBP and DBP. Further well-designed studies with larger samples are needed to ascertain the long-term effects of ALA on BP. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=447658, identifier PROSPERO: CRD42023447658.

Alpha-lipoic acid supplementation reverses the declining quality of oocytes exposed to cyclophosphamide

Cyclophosphamide (CY) is a chemotherapeutic drug that is commonly used to treat malignancies of the ovary, breast, and hematology, as well as autoimmune disorders. As a cofactor of mitochondrial multienzyme complexes, alpha lipoic acid (ALA) is well known for its antioxidant characteristics, which operate directly on the scavenging of reactive oxygen species (ROS) and indirectly on the intracellular recycling of other antioxidants. However, the underlying mechanisms through which CY exerts its toxic effects on meiosis and oocyte quality, as well as a viable approach for protecting oocyte quality and preserving fertility, remain unknown. In present study, immunostaining and fluorescence intensity quantification were applied to assess the effects of CY and ALA supplementation on the key processes during the oocyte meiotic maturation. Our results show that supplementing oocytes with ALA, a well-known antioxidant and free radical scavenger, can reverse CY-induced oocyte meiotic maturation failure. Specifically, we found that CY exposure caused oocyte meiotic failure by disrupting meiotic organelle dynamics and arrangement, as well as a prominently impaired cytoskeleton assembly. In addition, CY caused an abnormal distribution of mitochondrion and cortical granules, two indicators of oocyte cytoplasmic maturation. More importantly, we show that ALA supplementation effectively reverses CY-induced meiotic failure and oocyte quality decline by suppressing oxidative stress-induced DNA damage and apoptosis in oocytes. Collectively, our data reveal that ALA supplementation is a feasible approach to protect oocytes from CY-exposed deterioration, providing a better understanding of the mechanisms involved in chemotherapy-induced meiotic failure.

Effect of Alpha Lipoic Acid Supplementation on Oxidative Stress and Lipid Parameters in Women Diagnosed with Low-Grade Squamous Intraepithelial Lesions (LSILs): A Double-Blind, Randomized, Placebo-Controlled Trial.

Limited scientific evidence shows that alpha lipoic acid (ALA) can induce regression rates of low-grade squamous intraepithelial lesions (LSILs), but the mechanisms of these effects have not been elucidated. To gain a broader insight into its therapeutic potential and mechanisms of action, the effects of 3 months of supplementation with 600 mg of ALA on antioxidant and lipid status parameters in 100 patients with LSILs were investigated in a randomized, placebo-controlled study. The obtained results are discussed in terms of patients' initial metabolic status and diet quality (particularly nutritional intake of antioxidants). The obtained results showed that oxidative status biomarkers were not significantly affected by ALA supplementation. However, serum superoxide dismutase (SOD) activity was positively affected in the subgroup of patients with higher dietary antioxidant intake. Surprisingly, ALA supplementation resulted in a small but statistically significant increase in serum low density lipoprotein (LDL), and the observed effect was significantly affected by the initial lipid status of the participants. Larger studies are necessary to gain additional insights on the clinical significance of ALA as an antioxidant and hypolipemic agent and to optimize its potential application in LSIL treatment.

Alpha-lipoic acid attenuates heat stress-induced apoptosis via upregulating the heat shock response in porcine parthenotes

Heat stress (HS) is a long-standing hurdle that animals face in the living environment. Alpha-lipoic acid (ALA) is a strong antioxidant synthesized by plants and animals. The present study evaluated the mechanism of ALA action in HS-induced early porcine parthenotes development. Parthenogenetically activated porcine oocytes were divided into three groups: control, high temperature (HT) (42 °C for 10 h), and HT + ALA (with 10 µM ALA). The results show that HT treatment significantly reduced the blastocyst formation rate compared to the control. The addition of ALA partially restored the development and improved the quality of blastocysts. Moreover, supplementation with ALA not only induced lower levels of reactive oxygen species and higher glutathione levels but also markedly reduced the expression of glucose regulatory protein 78. The protein levels of heat shock factor 1 and heat shock protein 40 were higher in the HT + ALA group, which suggests activation of the heat shock response. The addition of ALA reduced the expression of caspase 3 and increased the expression of B-cell lymphoma-extra-large protein. Collectively, this study revealed that ALA supplementation ameliorated HS-induced apoptosis by suppressing oxidative and endoplasmic reticulum stresses via activating the heat shock response, which improved the quality of HS-exposed porcine parthenotes.

Alpha-lipoic acid supplementation corrects pathological alterations in cellular models of pantothenate kinase-associated neurodegeneration with residual PANK2 expression levels

BackgroundNeurodegeneration with brain iron accumulation (NBIA) disorders are a group of neurodegenerative diseases that have in common the accumulation of iron in the basal nuclei of the brain which are essential components of the extrapyramidal system. Frequent symptoms are progressive spasticity, dystonia, muscle rigidity, neuropsychiatric symptoms, and retinal degeneration or optic nerve atrophy. One of the most prevalent subtypes of NBIA is Pantothenate kinase-associated neurodegeneration (PKAN). It is caused by pathogenic variants in the gene of pantothenate kinase 2 (PANK2) which encodes the enzyme responsible for the first reaction on the coenzyme A (CoA) biosynthesis pathway. Thus, deficient PANK2 activity induces CoA deficiency as well as low expression levels of 4′-phosphopantetheinyl proteins which are essential for mitochondrial metabolism.MethodsThis study is aimed at evaluating the role of alpha-lipoic acid (α-LA) in reversing the pathological alterations in fibroblasts and induced neurons derived from PKAN patients. Iron accumulation, lipid peroxidation, transcript and protein expression levels of PANK2, mitochondrial ACP (mtACP), 4′′-phosphopantetheinyl and lipoylated proteins, as well as pyruvate dehydrogenase (PDH) and Complex I activity were examined.ResultsTreatment with α-LA was able to correct all pathological alterations in responsive mutant fibroblasts with residual PANK2 enzyme expression. However, α-LA had no effect on mutant fibroblasts with truncated/incomplete protein expression. The positive effect of α-LA in particular pathogenic variants was also confirmed in induced neurons derived from mutant fibroblasts.ConclusionsOur results suggest that α-LA treatment can increase the expression levels of PANK2 and reverse the mutant phenotype in PANK2 responsive pathogenic variants. The existence of residual enzyme expression in some affected individuals raises the possibility of treatment using high dose of α-LA.

The Use of Alpha-Lipoic Acid Supplementation in Diabetes: The Available Evidence

Dietary health supplements have been increasingly used in the treatment and prevention of chronic disorders. During the previous years, lipoic acid has been reported to have a beneficial effect on diabetes and some of its complications. The aim of this paper is to review the evidence provided by lipoic acid research findings relevant to its use in diabetes. Since, the1950s, there has been an accumulating experimental evidence showing that that lipoic acid, a naturally occurring substance, has a protective effects against the development of diabetes and its complications especially neuropathy. The beneficial use of oral lipoic acid in diabetic neuropathy has been reported mostly from Germany as early as the 1960s.

Cognitive and Mood Effect of Alpha-Lipoic Acid Supplementation in a Nonclinical Elder Sample: An Open-Label Pilot Study.

Memory disorders are common among elder people, and nonclinical cognitive decline is commonly experienced with age. Preclinical investigations have explored the possible role of alpha-lipoic acid (ALA), a known antioxidant compound abundant in vegetables and animal tissues, in reducing oxidative stress in the aging brain and preventing cognitive decline. However, clinical evidence is limited, and the few existing results are contrasting. In addition, while most of the existing trials have been focused on the effects of ALA administration in Alzheimer's disease (AD) or other types of dementia, studies evaluating its effects on nonclinical elder population are still missing. In the present open-label, pilot study, fifteen elder patients (mean age: 84.5 ± 5.77) received ALA at a daily dose of 600 mg/day for 12 weeks. General cognitive function, executive function, and mood symptom assessment were carried out at baseline and at the endpoint. Overall, ALA administration was generally well-tolerated (only one dropout due to gastrointestinal side effects). However, no statistically significant effects either on cognitive function, executive function, or mood were found. Despite several limitations, our study found no evidence of positive effects on cognition and mood after ALA administration in elder people without the diagnosis of AD or cognitive impairment. Further clinical trials are needed to better investigate ALA effectiveness on cognition and mood in elder subjects.