Radical S-Adenosylmethionine Enzymes in Human Health and Disease.

Radical S-adenosylmethionine (SAM) enzymes catalyze an astonishing array of complex and chemically challenging reactions across all domains of life. Of approximately 114,000 of these enzymes, 8 are known to be present in humans: MOCS1, molybdenum cofactor biosynthesis; LIAS, lipoic acid biosynthesis; CDK5RAP1, 2-methylthio-N(6)-isopentenyladenosine biosynthesis; CDKAL1, methylthio-N(6)-threonylcarbamoyladenosine biosynthesis; TYW1, wybutosine biosynthesis; ELP3, 5-methoxycarbonylmethyl uridine; and RSAD1 and viperin, both of unknown function. Aberrations in the genes encoding these proteins result in a variety of diseases. In this review, we summarize the biochemical characterization of these 8 radical S-adenosylmethionine enzymes and, in the context of human health, describe the deleterious effects that result from such genetic mutations.

α-lipoic acid ameliorates consequences of copper overload by up-regulating selenoproteins and decreasing redox misbalance.

α-lipoic acid (LA) is an essential cofactor for mitochondrial dehydrogenases and is required for cell growth, metabolic fuel production, and antioxidant defense. In vitro, LA binds copper (Cu) with high affinity and as an endogenous membrane permeable metabolite could be advantageous in mitigating the consequences of Cu overload in human diseases. We tested this hypothesis in 3T3-L1 preadipocytes with inactivated Cu transporter Atp7a; these cells accumulate Cu and show morphologic changes and mitochondria impairment. Treatment with LA corrected the morphology of Atp7a-/- cells similar to the Cu chelator bathocuproinedisulfonate (BCS) and improved mitochondria function; however, the mechanisms of LA and BCS action were different. Unlike BCS, LA did not decrease intracellular Cu but instead increased selenium levels that were low in Atp7a-/- cells. Proteome analysis confirmed distinct cell responses to these compounds and identified upregulation of selenoproteins as the major effect of LA on preadipocytes. Upregulation of selenoproteins was associated with an improved GSH:GSSG ratio in cellular compartments, which was lowered by elevated Cu, and reversal of protein oxidation. Thus, LA diminishes toxic effects of elevated Cu by improving cellular redox environment. We also show that selenium levels are decreased in tissues of a Wilson disease animal model, especially in the liver, making LA an attractive candidate for supplemental treatment of this disease.

The mitochondrion of Plasmodium falciparum is required for cellular acetyl-CoA metabolism and protein acetylation.

Coenzyme A (CoA) biosynthesis is an excellent target for antimalarial intervention. While most studies have focused on the use of CoA to produce acetyl-CoA in the apicoplast and the cytosol of malaria parasites, mitochondrial acetyl-CoA production is less well understood. In the current study, we performed metabolite-labeling experiments to measure endogenous metabolites in Plasmodium falciparum lines with genetic deletions affecting mitochondrial dehydrogenase activity. Our results show that the mitochondrion is required for cellular acetyl-CoA biosynthesis and identify a synthetic lethal relationship between the two main ketoacid dehydrogenase enzymes. The activity of these enzymes is dependent on the lipoate attachment enzyme LipL2, which is essential for parasite survival solely based on its role in supporting acetyl-CoA metabolism. We also find that acetyl-CoA produced in the mitochondrion is essential for the acetylation of histones and other proteins outside of the mitochondrion. Taken together, our results demonstrate that the mitochondrion is required for cellular acetyl-CoA metabolism and protein acetylation essential for parasite survival.

Injectable Hydrogel System Incorporating Black Phosphorus Nanosheets and Tazarotene Drug for Enhanced Vascular and Nerve Regeneration in Spinal Cord Injury Repair.

Spinal cord injury (SCI) often leads to cell death, vascular disruption, axonal signal interruption, and permanent functional damage. Currently, there are no clearly effective therapeutic options available for SCI. Considering the inhospitable SCI milieu typified by ischemia, hypoxia, and restricted neural regeneration, a novel injectable hydrogel system containing conductive black phosphorus (BP) nanosheets within a lipoic acid-modified chitosan hydrogel matrix (LAMC) is explored. The incorporation of tannic acid (TA)-modified BP nanosheets (BP@TA) into the LAMC hydrogel matrix significantly improved its conductivity. Further, by embedding a bicyclodextrin-conjugated tazarotene drug, the hydrogel showcased amplified angiogenic potential in vitro. In a rat model of complete SCI, implantation of LAMC/BP@TA hydrogel markedly improved the recovery of motor function. Immunofluorescence evaluations confirmed that the composite hydrogel facilitated endogenous angiogenesis and neurogenesis at the injury site. Collectively, this work elucidates an innovative drug-incorporated hydrogel system enriched with BP, underscoring its potential to foster vascular and neural regeneration.

Wearable and Recyclable Water-Toleration Sensor Derived from Lipoic Acid.

Flexible wearable sensors recently have made significant progress in human motion detection and health monitoring. However, most sensors still face challenges in terms of single detection targets, single application environments, and non-recyclability. Lipoic acid (LA) shows a great application prospect in soft materials due to its unique properties. Herein, ionic conducting elastomers (ICEs) based on polymerizable deep eutectic solvents consisting of LA and choline chloride are prepared. In addition to the good mechanical strength, high transparency, ionic conductivity, and self-healing efficiency, the ICEs exhibit swelling-strengthening behavior and enhanced adhesion strength in underwater environments due to the moisture-induced association of poly(LA) hydrophobic chains, thus making it possible for underwater sensing applications, such as underwater communication. As a strain sensor, it exhibits highly sensitive strain response with repeatability and durability, enabling the monitoring of both large and fine human motions, including joint movements, facial expressions, and pulse waves. Furthermore, due to the enhancement of ion mobility at higher temperatures, it also possesses excellent temperature-sensing performance. Notably, the ICEs can be fully recycled and reused as a new strain/temperature sensor through heating. This study provides a novel strategy for enhancing the mechanical strength of poly(LA) and the fabrication of multifunctional sensors.

Protective effect of alpha-lipoic acid and epalrestat on oxaliplatin-induced peripheral neuropathy in zebrafish.

INTRODUCTION/AIMS: Oxaliplatin is a platinum-based anti-cancer drug widely used in colorectal cancer patients, but it may cause peripheral neuropathy. As one of the main causes of oxaliplatin-induced peripheral neuropathy (OPN) is oxidative stress, which is also a key factor causing diabetic peripheral neuropathy (DPN), the aim of this study was to evaluate the preventive effects of alpha-lipoic acid (ALA) and epalrestat (EP), which are used for the treatment of DPN, in an OPN zebrafish model. METHODS: Tg(nbt:dsred) transgenic zebrafish, with sensory nerves in the peripheral lateral line, were treated with oxaliplatin, oxaliplatin/EP, and oxaliplatin/ALA for 4 days. A confocal microscope was used to visualize and quantify the number of axon bifurcations in the distal nerve ending. To analyze the formation of synapses on sensory nerve terminals, quantification of membrane-associated guanylate kinase (MAGUK) puncta was performed using immunohistochemistry. RESULTS: The number of axon bifurcations and intensity of MAGUK puncta were significantly reduced in the oxaliplatin-treated group compared with those in the embryo medium-treated group. In both the oxaliplatin/EP and oxaliplatin/ALA-treated groups, the number of axon bifurcations and intensity of MAGUK puncta were greater than those in the oxaliplatin-treated group (p < .0001), and no significant difference was observed between larvae treated with oxaliplatin/ALA 1 µM and oxaliplatin/EP 1 µM (p = .4292). DISCUSSION: ALA and EP have protective effects against OPN in zebrafish. Our findings show that ALA and EP can facilitate more beneficial treatment for OPN.

In vitro models for neuropathic pain phenotypic screening in brain therapeutics.

The discovery of brain therapeutics faces a significant challenge due to the low translatability of preclinical results into clinical success. To address this gap, several efforts have been made to obtain more translatable neuronal models for phenotypic screening. These models allow the selection of active compounds without predetermined knowledge of drug targets. In this review, we present an overview of various existing models within the field, examining their strengths and limitations, particularly in the context of neuropathic pain research. We illustrate the usefulness of these models through a comparative review in three crucial areas: i) the development of novel phenotypic screening strategies specifically for neuropathic pain, ii) the validation of the models for both primary and secondary screening assays, and iii) the use of the models in target deconvolution processes.

Influence of α-lipoic acid on longevity and stress resistance in Drosophila melanogaster fed with a high-fat diet.

Consumption of a high-fat diet is accompanied by the risks of obesity and early onset of age-associated complications for which dietary interventions are imperative to combat. α-lipoic acid has been shown to hinder diet-induced obesity and induce lifespan-extending efficacy in model organisms. In this study, α-lipoic acid was investigated for its efficacy in improving lifespan and stress resistance in the Canton-S strain of Drosophila melanogaster fed with a high-fat diet. Furthermore, as mating status significantly impacts survival in fruit flies, flies were reared in two experimental groups-group one, in which males and females were bred together, and group two, in which males and females were bred separately. In group one, α-lipoic acid improved the mean lifespan, reduced the fecundity of females, and reduced the mean body weight of flies at a dose range of 2-2.5 mM, respectively. In group two, α-lipoic acid improved the mean lifespan, reduced the fecundity of females, and reduced the mean body weight of flies at a dose range of 1-2.5 mM, respectively. Improved climbing efficiency was observed with α-lipoic acid at the dose range of 1.5-2.5 mM in flies of group one and 1-2.5 mM in flies of group two, respectively. Administration of α-lipoic acid improved resistance to oxidative stress in only female flies of group one at 2.5 mM, whereas in group two, both male and female flies exhibited enhanced resistance to oxidative stress with α-lipoic acid at a dose range of 2-2.5 mM, respectively. Male and female flies of only group one showed improved resistance to heat shock stress with α-lipoic acid at a dose range of 2-2.5 mM. Only female flies of group two exhibited a slight improvement in recovery time following cold shock with α-lipoic acid only at 2.5 mM. No significant change in resistance to starvation stress was observed with any dose of α-lipoic acid in either group of flies. To summarize, data from this study suggested a probable dose and gender-dependent efficacy of α-lipoic acid in flies fed with a high-fat diet, which was significantly influenced by the mating status of flies due to varied rearing conditions.

Anti-cancer effects of alpha lipoic acid, cisplatin and paclitaxel combination in the OVCAR-3 ovarian adenocarcinoma cell line.

BACKGROUND: Ovarian cancer is the leading cause of gynecological cancer deaths. One of the major challenges in treating ovarian cancer with chemotherapy is managing the resistance developed by cancer cells to drugs, while also minimizing the side effects caused by these agents In the present study, we aimed to examine the effects of a combination of alpha lipoic acid (ALA), with cisplatin and paclitaxel in ovarian cancer(OVCAR-3). METHODS: The cytotoxic effects of ALA, cisplatin and paclitaxel on OVCAR-3 cells were determined. Four groups were formed: Control, ALA, Cisplatin + Paclitaxel, ALA + Cisplatin + Paclitaxel. The effects of single and combined therapy on cell migration, invasion and colony formation were analyzed. Changes in the expression of genes related to apoptosis, cell adhesion and cell cycle were analyzed with Real-time polymerase chain reaction(RT-PCR). The oxidative stress index and The Annexin V test were performed. RESULTS: The reduction in rapamycin-insensitive companion of mTOR(RICTOR) expression in the ALA + Cisplatin + Paclitaxel group was found statistically significant(p < 0.05). The decrease in MMP-9 and - 11 expressions the ALA + Cisplatin + Paclitaxel group was statistically significant(p < 0.05). The lowest values for mitogen-activated protein kinase(MAPK) proteins were found in the ALA + Cisplatin + Paclitaxel group. No colony formation was observed in the Cisplatin + Paclitaxel and ALA + Cisplatin + Paclitaxel groups. The lowest wound healing at 24 h was seen in the ALA + Cisplatin + Paclitaxel group. CONCLUSIONS: This study is the first one to investigate the combined treatment of ALA, Cisplatin, Paclitaxel on OVCAR-3. While ALA alone was not effective, combined therapy with ALA, has been found to reduce cell invasion, especially wound healing in the first 24 h, along with tumor cell adhesion.

Mitochondrial dysfunction in Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome: prospect use of antioxidants and mitochondrial nutrients.

Fragile X syndrome (FXS) is a genetic disorder characterized by mutation in the FMR1 gene, leading to the absence or reduced levels of fragile X Messenger Ribonucleoprotein 1 (FMRP). This results in neurodevelopmental deficits, including autistic spectrum conditions. On the other hand, Fragile X-associated tremor/ataxia syndrome (FXTAS) is a distinct disorder caused by the premutation in the FMR1 gene. FXTAS is associated with elevated levels of FMR1 mRNA, leading to neurodegenerative manifestations such as tremors and ataxia.Mounting evidence suggests a link between both syndromes and mitochondrial dysfunction (MDF). In this minireview, we critically examine the intricate relationship between FXS, FXTAS, and MDF, focusing on potential therapeutic avenues to counteract or mitigate their adverse effects. Specifically, we explore the role of mitochondrial cofactors and antioxidants, with a particular emphasis on alpha-lipoic acid (ALA), carnitine (CARN) and Coenzyme Q10 (CoQ10). Findings from this review will contribute to a deeper understanding of these disorders and foster novel therapeutic strategies to enhance patient outcomes.

Improving Gene Delivery: Synergy between Alkyl Chain Length and Lipoic Acid for PDMAEMA Hydrophobic Copolymers.

In the field of gene delivery, hydrophobic cationic copolymers hold great promise. They exhibit improved performance by effectively protecting genetic material from serum interactions while facilitating interactions with cellular membranes. However, managing cytotoxicity remains a significant challenge, prompting an investigation into suitable hydrophobic components. A particularly encouraging approach involves integrating nutrient components, like lipoic acid, which is known for its antioxidant properties and diverse cellular benefits such as cellular metabolism and growth. In this study, a copolymer library comprising 2-(dimethylamino)ethyl methacrylate (DMAEMA) and lipoic acid methacrylate (LAMA), combined with either n-butyl methacrylate (nBMA), ethyl methacrylate (EMA), or methyl methacrylate (MMA), is synthesized. This enables to probe the impact of lipoic acid incorporation while simultaneously exploring the influence of pendant acyclic alkyl chain length. The inclusion of lipoic acid results in a notable boost in transfection efficiency  while maintaining low cytotoxicity. Interestingly, higher levels of transfection efficiency are achieved in the presence of nBMA, EMA, or MMA. However, a positive correlation between pendant acyclic alkyl chain length and cytotoxicity is observed. Consequently, P(DMAEMA-co-LAMA-co-MMA), emerges as a promising candidate. This is attributed to the optimal combination of low cytotoxic MMA and transfection-boosting LAMA, highlighting the crucial synergy between LAMA and MMA.

Discovery of neuroprotective Agents: Potent, brain Penetrating, lipoic acid derivatives for the potential treatment of ischemic stroke by regulating oxidative stress and inflammation - a Preliminary study.

Stroke poses a serious risk to the physical and mental health of patients. Endogenous compounds are widely used to treat ischemic stroke. Lipoic acid, a naturally occurring (R)-5-(1,2-dithiolan-3-yl)pentanoic acid, has therapeutic potential for the treatment of ischemic stroke. However, the direct application of lipoic acid is limited by its relatively low efficacy and instability. Therefore, there is a need to modify the structure of lipoic acid to improve its pharmaceutical capabilities. Currently, 37 lipoic acid derivatives have been synthesized, and compound AA-9 demonstrated optimal therapeutic potential in an in vitro model of induced oxidative damage using tert-butyl hydroperoxide (t-BHP). In addition, in vitro experiments have shown that compound AA-9 has an excellent safety profile. Subsequently, the therapeutic effect of AA-9 was significant in the rat MCAO ischemic stroke model, which may be attributed to the antioxidant and anti-inflammatory effects of compound AA-9 by activating PGC-1α and inhibiting NLRP3. Notably, compound AA-9 exhibited higher stability and better bioavailability properties than ALA in plasma stability and pharmacokinetic properties. In conclusion, AA-9 may be a promising neuroprotective agent for the treatment of ischemic stroke and warrants further investigation.

Polymeric nanocomposite electrode for enhanced electrochemical detection of α-lipoic acid: Application in neuroinflammation prevention and clinical analysis.

Using poly (vanillin-co-chitosan)/functionalized MWCNTs/GCE (PV-CS/f-MWCNTs/GCE) as a polymeric nanocomposite modified electrode, the present investigation has been conducted on the electrochemical detection of α-lipoic acid (α-LA) to prevent the activation of microglia inflammation of the nervous system. The manufacture of modified polymeric nanocomposite electrodes was carried out using the established electropolymerization process. Field emission scanning electron microscopy (FE-SEM) and X-ray diffraction (XRD) analyses of structure revealed that the electropolymerization of poly (vanillin-co-chitosan) on the surface of the f-MWCNTs modified electrode was successful. Vanillin-co-chitosan electropolymerization on f-MWCNTs as electroactive sheets can enhance the signal for α-LA electrochemical sensors, according to research on the electrochemical characteristics utilizing cyclic voltammetry (CV) and differential pulse voltammetry (DPV) methodologies. The PV-CS/f-MWCNTs/GCE demonstrated that it had a sensitivity of 0.04664 µA/µM, a detection limit of 0.012 µM, and an excellent response, linear range, and wide linear range to α-LA from 0 to 3000 µM. The results of the application of PV-CS/f-MWCNTs/GCE for determining the concentration of α-LA in a prepared real sample of human serum by DPV and human lipoic acid ELISA Kit analyses via standard addition method illustrated the substantial conformity between the findings of both assays. The results of the DPV analyses resulted in acceptable recovery values (97.60%-99.10%) and appropriate values of the Relative Standard Deviation (RSD) (3.58%-5.07%), which demonstrated the great applicability and accuracy of the results of PV-CS/f-MWCNTs/GCE for determining α-LA concentration in biological fluids and pharmaceutical specimens.

Outcomes of dietary alpha-lipoic acid on testicular vascularization, steroid hormones, and seminal quality in aged Baladi bucks.

BACKGROUND: Senescence is accompanied by a progressive decrease in male reproductive performance, mainly due to oxidative stress and endothelial dysfunction. Alpha lipoic acid (ALA) is a potent antioxidant, that diffuses freely in aqueous and lipid phases, possessing anti-inflammatory and anti-apoptotic properties. This study aimed to examine the effects of supplemental dietary ALA on testicular hemodynamics (TH), circulating hormones, and semen quality in aged goats. Twelve Baladi bucks were divided into two groups (n = 6 each); the first fed a basic ration and served as a control group (CON), while the second received the basic ration supplemented with 600 mg ALA/ kg daily for consecutive eight weeks (ALA). RESULTS: There were improvements in testicular blood flow in the ALA group evidenced by a lower resistance index (RI) and pulsatility index (PI) concurrent with higher pampiniform-colored areas/pixel (W3-W6). There were increases in testicular volume and decreases in echogenicity (W3-W5; ALA vs. CON). Compared to the CON, ALA-bucks had higher serum concentrations of testosterone, estradiol, and nitric oxide (W3-W5). There were enhancements in semen traits (progressive motility, viability, morphology, and concentration, alanine aminotransferase enzyme) and oxidative biomarkers (catalase, total antioxidant capacity, and malondialdehyde). CONCLUSIONS: ALA dietary supplementation (600 mg/kg diet) improved aged bucks' reproductive performance by enhancing the testicular volume, testicular hemodynamics, sex steroids, and semen quality.

Targeted nanoparticles triggered by plaque microenvironment for atherosclerosis treatment through cascade effects of reactive oxygen species scavenging and anti-inflammation.

Inflammatory factors and reactive oxygen species (ROS) are risk factors for atherosclerosis. Many existing therapies use ROS-sensitive delivery systems to alleviate atherosclerosis, which achieved certain efficacy, but cannot eliminate excessive ROS. Moreover, the potential biological safety concerns of carrier materials through chemical synthesis cannot be ignored. Herein, an amphiphilic low molecular weight heparin- lipoic acid conjugate (LMWH-LA) was used as a ROS-sensitive carrier material, which consisted of injectable drug molecules used clinically, avoiding unknown side effects. LMWH-LA and curcumin (Cur) self-assembled to form LLC nanoparticles (LLC NPs) with LMWH as shell and LA/Cur as core, in which LMWH could target P-selectin on plaque endothelial cells and competitively block the migration of monocytes to endothelial cells to inhibit the origin of ROS and inflammatory factors, and LA could be oxidized to trigger hydrophilic-hydrophobic transformation and accelerate the release of Cur. Cur released within plaques further exerted anti-inflammatory and antioxidant effects, thereby suppressing ROS and inflammatory factors. We used ultrasound imaging, pathology and serum analysis to evaluate the therapeutic effect of nanoparticles on atherosclerotic plaques in apoe-/- mice, and the results showed that LLC showed significant anti-atherosclerotic effects. Our finding provided a promising therapeutic nanomedicine for the treatment of atherosclerosis.

Ångstrom-scale gold particles loaded with alendronate via alpha-lipoic acid alleviate bone loss in osteoporotic mice.

Osteoporosis is a highly prevalent metabolic disease characterized by low systemic bone mass and deterioration of bone microarchitecture, resulting in reduced bone strength and increased fracture risk. Current treatment options for osteoporosis are limited by factors such as efficacy, cost, availability, side effects, and acceptability to patients. Gold nanoparticles show promise as an emerging osteoporosis therapy due to their osteogenic effects and ability to allow therapeutic delivery but have inherent constraints, such as low specificity and the potential for heavy metal accumulation in the body. This study reports the synthesis of ultrasmall gold particles almost reaching the Ångstrom (Ång) dimension. The antioxidant alpha-lipoic acid (LA) is used as a dispersant and stabilizer to coat Ångstrom-scale gold particles (AuÅPs). Alendronate (AL), an amino-bisphosphonate commonly used in drug therapy for osteoporosis, is conjugated through LA to the surface of AuÅPs, allowing targeted delivery to bone and enhancing antiresorptive therapeutic effects. In this study, alendronate-loaded Ångstrom-scale gold particles (AuÅPs-AL) were used for the first time to promote osteogenesis and alleviate bone loss through regulation of the WNT signaling pathway, as shown through in vitro tests. The in vivo therapeutic effects of AuÅPs-AL were demonstrated in an established osteoporosis mouse model. The results of Micro-computed Tomography, histology, and tartrate-resistant acid phosphatase staining indicated that AuÅPs-AL significantly improved bone density and prevented bone loss, with no evidence of nanoparticle-associated toxicity. These findings suggest the possible future application of AuÅPs-AL in osteoporosis therapy and point to the potential of developing new approaches for treating metabolic bone diseases using Ångstrom-scale gold particles.

Solubilization and stabilization of lipoic acid trisulfide by creation of various ß-cyclodextrin clathrates.

Lipoic acid trisulfide, a sulfane sulfur-containing trisulfide of α-lipoic acid, holds promise in pharmaceuticals, yet knowledge gaps persist regarding its synthesis, properties, and stability. Here, we synthesized the lipoic acid trisulfide with a purity exceeding 99% from α-lipoic acid on a gram scale and obtained novel ß-cyclodextrin clathrates (84%-95% yield). Differential scanning calorimetry confirmed the inclusion of lipoic acid trisulfide in ß-cyclodextrins. The resulting ß-cyclodextrin clathrates exhibited significant improvements in water solubility and thermal stability. This pioneering study demonstrated a novel approach to the practical preparation of trisulfide and its ß-cyclodextrin clathrates as active ingredients, paving the way for clinical development.

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.

To observe the clinical effect of lipoic acid combined with continuous positive airway pressure ventilation in treating obstructive sleep apnea-hypopnea syndrome and its effect on peripheral blood γ-aminobutyric acid and melatonin levels.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a common respiratory disease with potential lethality. At present, the commonly used treatment method is continuous positive airway pressure ventilation, but with the prolongation of the course of the disease, the effect of single ventilation on the improvement of oxidative stress levels is not good. Lipoic acid is a commonly used antioxidant in clinics. In this paper, lipoic acid combined with continuous positive airway pressure ventilation is used to explore whether it has a better therapeutic effect on patients. AIM: To probe into the clinical efficacy of lipoic acid combined with continuous positive airway pressure ventilation in the therapy of OSAHS. METHODS: 82 patients with OSAHS who were cured in our hospital from March 2021 to September 2022 were prospectively collected as subjects. Based on different treatment methods, patients were grouped into a control group (43 cases) and an observation group (39 cases). The control group was treated with continuous positive airway pressure (CPAP), and the observation group was treated with lipoic acid based on control group. The therapeutic effects were measured by apnea hypopnea index (AHI), oxygen saturation (SpO2), mean oxygen saturation (MSpO2), serum malondialdehyde (MDA), superoxide dismutase (SOD), hypoxia inducible factor-1α (HIF-1α) levels, peripheral blood γ-aminobutyric acid, melatonin levels. RESULTS: The clinical effectiveness of the observation group was better (P < 0.05). After treatment, AHI, the levels of MDA and HIF-1α in the observation group were lower and SpO2, MSpO2 and the level of SOD, γ- aminobutyric acid, and melatonin were higher than those in the control group (P < 0.05). The levels of γ- aminobutyric acid and melatonin were negatively correlated with the severity of symptoms, ESS, and AIS scores (P < 0.05). CONCLUSIONS: The clinical effect of lipoic acid combined with CPAP in the treatment of OSAHS is better, and it has a positive effect on the levels of γ-aminobutyric acid and melatonin in peripheral blood. Lipoic acid was added to the original method for treatment, and the therapeutic effect was greatly improved.

Alpha lipoic acid administration improved both peripheral sensitivity to insulin and liver clearance of insulin reducing potential risk of diabetes and nonalcoholic fatty liver disease in overweight/obese PCOS patients.

OBJECTIVE: To evaluate the effects of alpha lipoic acid (ALA) on hormonal and metabolic parameters in a group of overweight/obese Polycystic Ovary Syndrome (PCOS) patients. METHODS: This was a retrospective study in which thirty-two overweight/obese patients with PCOS (n = 32) not requiring hormonal treatment were selected from the database of the ambulatory clinic of the Gynecological Endocrinology Center at the University of Modena and Reggio Emilia, Italy. The hormonal profile, routine exams and insulin and C-peptide response to oral glucose tolerance test (OGTT) were evaluated before and after 12 weeks of complementary treatment with ALA (400 mg/day). Hepatic Insulin Extraction (HIE) index was also calculated. RESULTS: ALA administration significantly improved insulin sensitivity and decreased ALT and AST plasma levels in all subjects, though no changes were observed on reproductive hormones. When PCOS patients were subdivided according to the presence or absence of familial diabetes background, the higher effects of ALA were observed in the former group that showed AST and ALT reduction and greater HIE index decrease. CONCLUSION: ALA administration improved insulin sensitivity in overweight/obese PCOS patients, especially in those with familial predisposition to diabetes. ALA administration improved both peripheral sensitivity to insulin and liver clearance of insulin. Such effects potentially decrease the risk of nonalcoholic fat liver disease and diabetes in PCOS patients.