Search Results (17)

Alpha-lipoic acid (ALA) is well-known for its antioxidant and anti-inflammatory functions in various disease models. Here, we tested whether pre-exposure to ALA can protect the testes from cellular damage caused by scrotal heat shock (HS) in mice. Methods: Thirty-six Swiss albino mice were divided into control (CTRL, n = 6), HS (n = 10), and two ALA dose (HS + ALA 200 mg/kg, n = 10; and HS + ALA 400 mg/kg, n = 10) groups. ALA supplementation was administered orally for 30 days. Subsequently, the animals, except the controls, were subjected to an HS water bath at 43 °C for 20 min. Two days later, they were euthanized, and biometric data from gonads and accessory sexual glands, testicular samples for histomorphometric and immunohistochemical analyses, and sperm from the epididymis cauda were obtained for evaluation. Results: Animals submitted to HS had a lower body weight, decreased relative mass of testes and prostate, reduced seminiferous epithelium height and tubular diameter, and increased degeneration in seminiferous tubules. Additionally, sperm analysis showed a reduced linear progressive velocity (VSL) and straightness (STR), increased midpiece defects, and fewer sperm with functional membranes. Immunohistochemical evaluation revealed a reduced superoxide dismutase (SOD1) staining intensity in the testes. Preventive exposure to ALA at 200 mg/kg did not normalize the relative testicular mass, but it reduced the number of giant cells, decreased midpiece defects, normalized the number of sperm with functional membranes, and partially preserved SOD1 expression. Although animals treated with ALA 400 mg/kg showed an improvement in relative testicular mass, this dose was less efficient in other parameters. Conclusions: This study showed that while 30 days of oral ingestion of ALA before the induction of acute degenerative injury did not fully protect male mouse gonads at the tissue level, some parameters related to testicular function and sperm quality showed a partial improvement. Full article

Alpha-lipoic acid (ALA, also known as thioctic acid) was discovered nearly 90 years ago and began to be used in clinical practice in the late 1950s. Numerous nonclinical and clinical studies have investigated ALA for treating diabetic peripheral neuropathy (DPN) and various other diseases. The rising global prevalence of DPN necessitates timely treatment; however, there is currently no effective cure. Current guideline-recommended therapies for DPN provide symptom relief rather than modifying the disease. Among the pathogenesis-oriented therapies, ALA holds a unique position as a universal antioxidant, essential for every cell in the body. This review highlights the ongoing issues and challenges in using ALA to treat DPN. While confronting a complex disease with poorly understood pathophysiology, we also have an endogenous substance with pleiotropic effects on all cells in the human body. It becomes clear that this is a highly multifactorial process that will likely never be precisely defined. This does not diminish the significance of ALA in treating DPN but underscores the need for a deeper understanding of when to start therapy, dosage, duration, and monitoring. In this comprehensive review, we evaluate the achievements of the past 70 years and highlight gaps in ALA’s role in treating DPN. Full article

Background: Multiple sclerosis (MS) is a chronic inflammatory disease characterized by demyelination in the central nervous system (CNS). Despite the availability of interventions for disease exacerbations and symptomatic management, EM remained without a cure. Oxidative stress has been implicated in the MS demyelination mechanism. Adjuvant therapies like α-lipoic acid (ALA) have garnered interest for their potential to mitigate oxidative damage and control MS symptoms. ALA is found naturally in vegetables and red meat and can also be synthesized in mitochondria through enzymatic reactions involving octanoic acid and cysteine. However, its bioavailability from dietary sources is limited, prompting an investigation into supplemental forms. We conducted a systematic review and meta-analysis to assess the effect of ALA on disability in randomized clinical trials (RCTs) for MS. Methods: Records were searched until June 2023 (CRD42023397760). Five RCTs evaluated ALA’s effect on MS progression using the Expanded Disability Status Scale (EDSS). The quality of evidence was assessed using GRADE, and publication bias was evaluated using Egger’s and Begg’s tests. Results: Following the selection process, five studies were included involving 179 patients (87 placebo and 92 ALA). Oral administration of racemic ALA (R/S-ALA) at 600 mg twice daily reduced EDSS, indicating a potential for ALA supplementation to mitigate MS disability. The North American trials (SPMS patients) did not show heterogeneity, while Asian studies (RRMS patients) were moderated. The quality of evidence was high without publication bias. Conclusions: ALA treatment reduce EDSS scores. However, further studies are warranted to establish the role of ALA as an adjuvant in clinical practice in long-term follow-up (>2 years) RCTs. Full article

Vincristine, a vinca alkaloid, is used in chemotherapy protocols for cancers such as acute leukemia, Hodgkin’s disease, neuroblastoma, cervical carcinoma, lymphomas, breast cancer, and melanoma. Among the common adverse effects of vincristine is peripheral neuropathy, with most patients receiving a cumulative dose over 4 mg/m² who develop varying degrees of sensory neuropathy. The onset of vincristine-induced peripheral neuropathy can greatly affect patients’ quality of life, often requiring dose adjustments or the discontinuation of treatment. Moreover, managing vincristine-induced peripheral neuropathy is challenging, with few effective therapeutic strategies available. In the past decade, preclinical studies have explored diverse substances aimed at preventing or alleviating VIPN. Our review consolidates these findings, focusing on the analgesic efficacy and potential mechanisms of various agents, including pharmaceutical drugs, natural compounds, and antioxidants, that show promise in reducing neuropathic pain and protecting neural integrity in preclinical models. Key novel therapeutic options, such as metabolic agents (liraglutide), enzyme inhibitors (ulinastatin), antipsychotics (aripiprazole), interleukin-1 receptor antagonists (anakinra), hormones (oxytocin), and antioxidants (thioctic acid), are highlighted for their neuroprotective, anti-inflammatory, and antioxidant effects. Through this synthesis, we aim to enhance the current understanding of VIPN management by identifying pharmacological strategies that target critical molecular pathways, laying the groundwork for future clinical studies. By clarifying these novel pharmacological approaches and elucidating their mechanisms of action, this review provides a foundation for developing more effective VIPN treatment strategies to ultimately improve patient outcomes. Full article

Liquid-filled hard gelatin capsules may have pertinent advantages both for therapeutic effect and extemporaneous preparations of medicines. Alpha lipoic acid is a substance used in medicines and dietary supplements and there is a need for creating an appropriate formulation which would be suitable for each individual patient or consumer. Based on its biopharmaceutical and physical chemical characteristics, eight different capsule formulations were designed and characterized. Silicon dioxide was added to form a semisolid content and prevent leakage. The formulation filled with alpha lipoic acid solution in polyethylene glycol 400 showed the best performance. Although the addition of silicon dioxide to the formulation with polyethylene glycol 400 led to a change in both flow character and viscosity, the release rate did not show a statistically significant decrease (more than 85% of content was released after 5 min testing). Applied technique is a simple and an appropriate approach for compounding and could be used for other substances with similar properties. Full article

A carbon dot-functionalized solution-gated graphene transistor (CD-SGGT) was designed and prepared via the modification of CDs on the gate of SGGT. The above CDs were hydrothermally synthesized using DL-thioctic acid and triethylenetramine as C, N and S sources. The average size of CDs was ~6.2 nm, and there were many amino and carboxyl groups on the CDs’ surfaces. The CDs was then used as a probe for preparation of CD-SGGT sensor for the cobalt(II) (Co²⁺) ions detection. The CD-SGGT sensor showed excellent sensitivity and high selectivity. Remarkably, the limit of detection (LOD) reached 10⁻¹⁹ M. The linear detection range was obtained from 10⁻¹⁹ to 10⁻¹⁵ M. Additionally, the CD-SGGT also showed fast response and good stability. Full article

An electrochemical biosensor based on chitosan- and thioctic-acid-modified nanoporous gold (NPG) co-immobilization glycerol kinase (GK) and glycerol-3-phosphate oxidase (GPO) was constructed for glycerol determination in wine. The NPG, with the properties of porous microstructure, large specific surface area, and high conductivity, was beneficial for protecting the enzyme from inactivation and denaturation and enhancing electron transfer in the modified electrode. The co-immobilization of the enzyme by chitosan-embedding and thioctic-acid-modified NPG covalent bonding was beneficial for improving the catalytic performance and stability of the enzyme-modified electrode. Ferrocene methanol (Fm) was used as a redox mediator to accelerate the electron transfer rate of the enzyme-modified electrode. The fabricated biosensor exhibited a wide determination range of 0.1–5 mM, low determination limit of 77.08 μM, and high sensitivity of 9.17 μA mM⁻¹. Furthermore, it possessed good selectivity, repeatability, and stability, and could be used for the determination of glycerol in real wine samples. This work provides a simple and novel method for the construction of biosensors, which may be helpful to the application of enzymatic biosensors in different determination scenarios. Full article

Renal and cardiac impairments are frequent events in the presence of hypertension. Organ damage is mainly linked to oxidative stress due to high blood pressure and may be reduced by antioxidant supplementation. Alpha-lipoic acid (ALA) is one of most effective antioxidants. It is widely used as a nutritional supplement in a racemic mixture (+/–), even though the (+)-enantiomer is biologically active. This study was designed to investigate the effect of treatment with (+/–)-ALA and its enantiomers on renal and heart parenchyma in spontaneously hypertensive rats (SHR), using immunochemical and immunohistochemical techniques. The results confirmed that the oxidative mechanisms of organ alterations, due to hypertension, and characterized by glomerular and tubular lesions, left ventricular hypertrophy, and fibrosis but not by apoptosis were accompanied by proteins’ and nucleic acids’ oxidation. We found greater effectiveness of (+)-ALA compared to (+/−)-ALA in reducing oxidative stress, cardiac and renal damages in SHR. To conclude, these data propose (+)-ALA as one of the more appropriate antioxidant molecules to prevent renal and cardiac alterations associated with hypertension. Full article

Alpha-lipoic acid (ALA, thioctic acid), a naturally-occurring essential dithiol compound, has become a common ingredient in many pharmaceutical and food supplement products (FSP), used in oxidative stress-dependent pathologies; oral bioavailability of ALA is limited by pharmacokinetic particularities that reduce its therapeutic efficacy-reduced solubility, lack of gastric stability and hepatic degradation, doubled by formulation hinders. The objectives were to develop a solid oral 600 mg ALA FSP to obtain an optimal pharmaceutical profile compared to a reference listed drug (RLD) with a similarity factor f₂ 50. A comparative dissolution study was performed; an HPLC method was used for ALA quantification. After planning combinatory simulations (formulation stage), two prototype formulas (#1 and #2) were manufactured and further optimized by adjusting ALA physical characteristics and the excipients quantities (#3 and #4) in order to achieve the Quality Target Product Profile. A misshapen of ALA’s in vitro release was observed for #3 Formula (f₂ = 31.6); the optimal profile was obtained for Formula #4 (f₂ = 58.5). A simple quantitative formula is not enough to assure good ALA bioavailability; the formulation needs multiple compounding modulations under physicochemical compatibility algorithms, with multiple dissolution profiles testing back-ups. It is essential to ensure a formulation with an in vitro dissolution comparable with the RLD, allowing the compound to reach its target level to assure the optimum claimed antioxidant activity of ALA at the cellular level, even for food supplement formulations. Full article

Alpha-lipoic acid (ALA) is a natural short-chain fatty acid that has attracted great attention in recent years as an antioxidant molecule. However, some concerns have been recently raised regarding its safety profile. To address the issue, we aimed to assess ALA safety profile through a systematic review of the literature and a meta-analysis of the available randomized placebo-controlled clinical studies. The literature search included EMBASE, PubMed Medline, SCOPUS, Google Scholar, and ISI Web of Science by Clarivate databases up to 15th August 2020. Data were pooled from 71 clinical studies, comprising 155 treatment arms, which included 4749 subjects with 2558 subjects treated with ALA and 2294 assigned to placebo. A meta-analysis of extracted data suggested that supplementation with ALA was not associated with an increased risk of any treatment-emergent adverse event (all p > 0.05). ALA supplementation was safe, even in subsets of studies categorized according to smoking habit, cardiovascular disease, presence of diabetes, pregnancy status, neurological disorders, rheumatic affections, severe renal impairment, and status of children/adolescents at baseline. Full article

The constitutive activation of the mechanistic target of rapamycin complex 1 (mTORC1) leads to the overproduction of apoB-containing triacylglycerol-rich lipoproteins in HepG2 cells. R-α-lipoic acid (LA) and 4-phenylbutyric acid (PBA) have hypolipidemic function but their mechanisms of action are not well understood. Here, we reported that LA and PBA regulate hepatocellular lipid metabolism via distinct mechanisms. The use of SQ22536, an inhibitor of adenylyl cyclase, revealed cAMP’s involvement in the upregulation of CPT1A expression by LA but not by PBA. LA decreased the secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) in the culture media of hepatic cells and increased the abundance of LDL receptor (LDLR) in cellular extracts in part through transcriptional upregulation. Although PBA induced LDLR gene expression, it did not translate into more LDLR proteins. PBA regulated cellular lipid homeostasis through the induction of CPT1A and INSIG2 expression via an epigenetic mechanism involving the acetylation of histone H3, histone H4, and CBP-p300 at the CPT1A and INSIG2 promoters. Full article

Thioctic acid is a multipotent antioxidant compound existing as dextrorotatory (+), eutomer and naturally occurring and levorotatory (−). It has been proven to help fight many pathologies and is sold as racemate. In agreement with studies claiming a greater biopotency of the eutomer compared to the levorotatory compound, we recently preclinically and clinically showed that (+) thioctic acid is a pain-reliever as effective as double-dosed racemate. We investigated acute and subchronical toxicity of (+/−) thioctic acid, (−) thioctic acid, (+) thioctic acid and (+) salt thioctic acid on Sprague–Dawley rats. For acute toxicity, compounds were administered intraperitoneally (i.p.) with a single-injection at 125, 240, 360, 480 µmol/kg, then rodents were tested for motorial coordination and minimum lethal dose (LDmin). A subtoxic dose (360 µmol/kg) was administered i.p. for 15 days and we finally evaluated motorial impairment, glycemia, organ toxicity, and apoptosis state. Acutely administered, the highest doses of all thioctic acid compounds negatively affected motorial ability and (−) thioctic acid LDmin resulted higher than the others. Subchronic administrations caused overall body weight loss, motorial impairment, mass loss in some organs. (+/−) and (−) thioctic acid injections enhanced caspase-3 activity in some organs, (−) enantiomer-treated animals displayed more marked organ toxicity signs. Together with our previous study on the biologic role of enantiomers, these data suggest a therapeutic use of (+) enantiomer-based formulations, thus lowering dose and toxicity without affecting the positive effects brought by the drug. Full article

Sarcopenia is a clinical problem associated with several pathological and non-pathological conditions. The aim of the present research is the evaluation of the pharmacological profile of the leucine metabolite β-hydroxy-β-methyl butyrate (HMB) associated with the natural R(+) stereoisomer of lipoic acid (R(+)LA) in a cellular model of muscle wasting. The C2C12 cell line is used as myoblasts or is differentiated in myotubes, sarcopenia is induced by dexamethasone (DEX). A Bonferroni significant difference procedure is used for a post hoc comparison. DEX toxicity (0.01–300 µM concentration range) is evaluated in myoblasts to measure cell viability and caspase 3 activation after 24 h and 48 h; cell incubation with 1 µM DEX for 48 h is chosen as optimal treatment for decreasing cell viability and increasing caspase 3 activity. R(+)LA or HMB significantly prevents DEX-induced cell mortality; the efficacy is improved when 100 µM R(+)LA is combined with 1 mM HMB. Regarding myoblasts, this combination significantly reduces DEX-evoked O₂⁻ production and protein oxidative damage. During the early phase of myotube formation, the mixture preserves the number of myogenin-positive cells, whereas it completely prevents the DEX-dependent damage in a later phase of myotube differentiation (7 days), as evaluated by cell diameter and percentage of multinucleated cells. R(+)LA in association with HMB is suggested for sarcopenia therapy. Full article

α-lipoic acid (ALA, thioctic acid) is an organosulfur component produced from plants, animals, and humans. It has various properties, among them great antioxidant potential and is widely used as a racemic drug for diabetic polyneuropathy-associated pain and paresthesia. Naturally, ALA is located in mitochondria, where it is used as a cofactor for pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase complexes. Despite its various potentials, ALA therapeutic efficacy is relatively low due to its pharmacokinetic profile. Data suggests that ALA has a short half-life and bioavailability (about 30%) triggered by its hepatic degradation, reduced solubility as well as instability in the stomach. However, the use of various innovative formulations has greatly improved ALA bioavailability. The R enantiomer of ALA shows better pharmacokinetic parameters, including increased bioavailability as compared to its S enantiomer. Indeed, the use of amphiphilic matrices has capability to improve ALA bioavailability and intestinal absorption. Also, ALA’s liquid formulations are associated with greater plasma concentration and bioavailability as compared to its solidified dosage form. Thus, improved formulations can increase both ALA absorption and bioavailability, leading to a raise in therapeutic efficacy. Interestingly, ALA bioavailability will be dependent on age, while no difference has been found for gender. The present review aims to provide an updated on studies from preclinical to clinical trials assessing ALA’s usages in diabetic patients with neuropathy, obesity, central nervous system-related diseases and abnormalities in pregnancy. Full article

Water soluble gold nanoparticles protected by lipoic acid were obtained and further functionalized by standard coupling reaction with 1-naphtylamine, 4-aminoantipyrine, and 4′-aminobenzo-15-crown-5 ether. Derivatives of lipoic acid with 1-naphtylamine, 4-aminoantipyrine, and 4′-aminobenzo-15-crown-5 ether were also obtained and characterized. All these were tested for their antimicrobial activity, as well as for their influence on mammalian cell viability and cellular cycle. In all cases a decreased antimicrobial activity of the obtained bioactive nanoparticles was observed as compared with the organic compounds, proving that a possible inactivation of the bioactive groups could occur during functionalization. However, both the gold nanoparticles as well as the functionalized bioactive nanosystems proved to be biocompatible at concentrations lower than 50 µg/mL, as revealed by the cellular viability and cell cycle assay, demonstrating their potential for the development of novel antimicrobial agents. Full article