RESUMEN

α-Lipoic acid possesses remarkable antioxidant activity; however, its poor lipid solubility greatly restricts its practical utilization. The present study was the first (i) to synthesize a novel lipophilic antioxidant of octacosanol lipoate and (ii) to assess its antioxidant potency in sunflower oil by hydrogen nuclear magnetic resonance (1H NMR) spectroscopy. In brief, octacosanol lipoate was successfully synthesized using octacosanol and lipoic acid as substrates and Candida sp. 99-125 lipase as a catalyst. The conversion of octacosanol lipoate could reach as high as 98.1% within merely 2 h, with an overall yield of 87.9%. The hydrophobicity of lipoic acid was significantly enhanced upon esterification with octacosanol. Interestingly, both traditional methods and 1H NMR analysis consistently indicated that octacosanol lipoate exhibited superior antioxidant activity compared with butyl hydroxytoluene at high temperatures. It was concluded that octacosanol lipoate has the potential to be developed into a safe and efficient natural antioxidant which can be utilized not only in daily cooking oils but also in frying oils.

RESUMEN

Oxytetracycline (OTC) is a widely employed antibiotic in veterinary treatment and in the prevention of infections, potentially leaving residues in animal-derived food products, such as milk, that are consumed by humans. Given the detrimental effects of prolonged human exposure to antibiotics, it has become imperative to develop precise and sensitive methods for monitoring the presence of OTC in food. Herein, we describe the development and results of a preliminary label-free electrochemical aptasensor with antifouling properties designed to detect OTC in milk samples. The sensor was realized by modifying a gold screen-printed electrode with α-lipoic acid-NHS and an amine-terminated aptamer. Different electrochemical techniques were used to study the steps of the fabrication process and to quantify OTC in the presence of the Fe(CN)64-/Fe(CN)63- redox couple The detectable range of concentrations satisfy the maximum residue limits set by the European Union, with an limit of detection (LOD) of 14 ng/mL in phosphate buffer (BP) and 10 ng/mL in the milk matrix, and a dynamic range of up to 500 ng/mL This study is a steppingstone towards the implementation of a sensitive monitoring method for OTC in dairy products.

Asunto(s)

Aptámeros de Nucleótidos , Técnicas Biosensibles , Técnicas Electroquímicas , Leche , Oxitetraciclina , Oxitetraciclina/análisis , Oxitetraciclina/química , Técnicas Electroquímicas/métodos , Técnicas Biosensibles/métodos , Leche/química , Aptámeros de Nucleótidos/química , Animales , Límite de Detección , Oro/química , Electrodos , Antibacterianos/análisis , Antibacterianos/química , Humanos

RESUMEN

Background: In recent years, minimally invasive treatment options for lumbar disc herniation, such as percutaneous laser disc decompression (PLDD), have been introduced to avoid more invasive surgical methods. Combining these minimally invasive approaches with nutraceuticals that are effective in neuroprotection and pain management may lead to better long-term outcomes. Methods: The present study evaluated the beneficial effects of a new oral food supplement composed of acetyl-L-carnitine, α-lipoic acid, quercetin, bromelain, pantothenic acid, and vitamins C, B1, B2, B6, and B12 in patients with neuropathic pain due to herniated lumbar discs treated with PLDD. Patients were divided into two groups of 26 patients each: group A underwent PLDD alone, while group B underwent PLDD followed by a dietary supplement for two months after surgery. Preoperative VAS scores for leg pain were recorded for both groups and no significant difference was observed (8.7 for Group A and 8.6 for Group B). Results: In Group A, the mean postoperative VAS score for leg pain at a 1-month follow-up was 2.5, which remained stable at 3 months. In Group B, the mean postoperative VAS score was 2.0 at 1-month and improved to 1.6 at the 3-month follow-up. According to self-reported leg pain assessments, 66.5% of the patients using the dietary supplement reported a significantly better pain condition, and 43.5% reported a somewhat better situation. In contrast, 7.7% of the patients who underwent PLDD alone reported no changes in leg pain at the final follow-up. Conclusions: The results of our study indicate that the oral food supplement could provide a safe and effective treatment in patients with painful radiculopathy, enhancing the recovery of sensory fiber function in lumbar nerve roots after surgical lumbar disc decompression.

RESUMEN

Alzheimer's disease is associated with a progressive loss of neurons and synaptic connections in the cholinergic system. Oxidative stress contributes to neuronal damages and to the development of amyloid plaques and neurofibrillary tangles. Therefore, antioxidants have been widely studied to mitigate the progression of Alzheimer's disease, and among these, lipoic acid has demonstrated a neuroprotective effect. Here, we present the synthesis, the molecular modelling, and the evaluation of lipoic acid-donepezil hybrids based on O-desmethyldonepezil. As compounds 5 and 6 display a high inhibition of acetylcholinesterase (IC50 = 7.6 nM and 9.1 nM, respectively), selective against butyrylcholinesterase, and a notable neuroprotective effect, slightly better than that of lipoic acid, the present study suggests that O-desmethyldonepezil could serve as a platform for the straightforward design of donepezil hybrids.

Asunto(s)

Acetilcolinesterasa , Enfermedad de Alzheimer , Butirilcolinesterasa , Inhibidores de la Colinesterasa , Donepezilo , Indanos , Fármacos Neuroprotectores , Piperidinas , Ácido Tióctico , Ácido Tióctico/química , Ácido Tióctico/farmacología , Ácido Tióctico/síntesis química , Donepezilo/farmacología , Donepezilo/química , Donepezilo/síntesis química , Enfermedad de Alzheimer/tratamiento farmacológico , Piperidinas/química , Piperidinas/farmacología , Piperidinas/síntesis química , Indanos/química , Indanos/farmacología , Indanos/síntesis química , Humanos , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Acetilcolinesterasa/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/síntesis química , Fármacos Neuroprotectores/química , Butirilcolinesterasa/metabolismo , Relación Estructura-Actividad , Estructura Molecular , Relación Dosis-Respuesta a Droga , Modelos Moleculares

RESUMEN

Breast cancer is the most common cancer among women worldwide, and adjuvant radiotherapy (RT) following tumor removal is one of the most commonly used treatments for breast cancer. However, the high risk of tumor recurrence and inevitable radiation skin injury after RT remain fatal problems, seriously challenging the patient's postoperative rehabilitation. Herein, a multifunctional poly (lipoic acid)-based hydrogel is constructed through one-step heating the mixture of α-lipoic acid (LA)/arginine (Arg)/silk fibroin (SF), without introducing any non-natural molecules. The multiple synergistic interactions among LA, Arg, and SF not only enhance the solubilization of LA in aqueous systems but also stabilize poly(lipoic acid) through strong salt bridge hydrogen bonds and ionic hydrogen bonds. Intriguingly, the LA-based surfactant induced ß-sheet transformation of SF can further modulate the bulk strength of the hydrogel. Regulating the content of LA in hydrogels not only allows efficient control of hydrogel bioactivity but also enables the evolution of hydrogels from injectable forms to adhesive patches. Based on the different biological activities and forms of hydrogels, they can be implanted internally or applied externally on the mice's skin, achieving simultaneous prevention of tumor recurrence post-surgery and assistance in treating radiation-induced skin damage after radiotherapy.

RESUMEN

Developing versatile ionoelastomers, the alternatives to hydrogels and ionogels, will boost the advancement of high-performance ionotronic devices. However, meeting the requirements of bio-derivation, high toughness, high stretchability, autonomous self-healing ability, high ionic conductivity, reprocessing, and favorable recyclability in a single ionoelastomer remains a challenging endeavor. Herein, a dynamic covalent and supramolecular design, lipoic acid (LA)-based dynamic covalent ionoelastomer (DCIE), is proposed via melt building covalent adaptive networks with hierarchically dynamic bonding (CAN-HDB), wherein lithium bonds aid in the dissociation of ions and the integration of dynamic disulfide metathesis, lithium bonds, and binary hydrogen bonds enhances the mechanical performances, self-healing capability, reprocessing, and recyclability. Therefore, the trade-off among mechanical versatility, ionic conductivity, self-healing capability, reprocessing, and recyclability is successfully handled. The obtained DCIE demonstrates remarkable stretchability (1011.7%), high toughness (3877 kJ m-3), high ionic conductivity (3.94 × 10-4 S m-1), outstanding self-healing capability, reprocessing for 3D printing, and desirable recyclability. Significantly, the selective ion transport endows the DCIE with multisensory feature capable of generating continuous electrical signals for high-quality sensations towards temperature, humidity, and strain. Coupled with the straightforward methodology, abundant availability of LA and HPC, as well as multifunction, the DCIEs present new concept of advanced ionic conductors for developing soft ionotronics.

RESUMEN

BACKGROUND: Kidney diseases are a major global health problem affecting millions of people. Despite this, there is as yet no effective drug therapy improving outcome in patients with renal disease. The aim of this study was to examine the nephroprotective effect of α-lipoic acid (ALA) in vitro and to examine the effect of ALA administered in vivo on the production of reactive sulfur species (RSS), including hydrogen sulfide (H2S) and compounds containing sulfane sulfur. METHODS: The effect of ALA was studied in vitro by determining the viability of human embryonic kidney cells (HEK293) in normoxic and hypoxic conditions as well as in vivo in two groups of chronic kidney disease (CKD) patients: non-dialyzed (ND) and undergoing continuous ambulatory peritoneal dialysis (PD) after 30 days of ALA supplementation. RESULTS: The results revealed that the viability of HEK293 cells was significantly decreased by hypoxic conditions, while ALA administered during hypoxia increased the viability to the level observed in normoxic conditions. Studies performed in plasma of CKD patients after ALA supplementation suggested that ALA did not affect the parameters of oxidative stress, while significantly increased the level of reactive sulfane sulfur in both ND and PD patients suffering from CKD. The results suggest that ALA can exert nephroprotective effects which are related to sulfane sulfur production.

Asunto(s)

Insuficiencia Renal Crónica , Ácido Tióctico , Humanos , Ácido Tióctico/farmacología , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/tratamiento farmacológico , Células HEK293 , Masculino , Femenino , Supervivencia Celular/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Persona de Mediana Edad , Antioxidantes/farmacología , Sulfuro de Hidrógeno/farmacología

RESUMEN

Advanced glycation end products (AGEs) are the final products of the Maillard reaction, formed through the interaction of carbohydrates and proteins. Reactive dicarbonyl compounds such as methylglyoxal (MGO) serve as precursors for AGEs formation. Elevated levels of MGO/AGEs are observed in conditions like obesity, polycystic ovarian syndrome (PCOS), and diabetes, negatively impacting oocyte development. Previous studies have shown that hydrogen sulfide, a gasotransmitter with anti-AGEs effects, is produced in a process influenced by vitamin B6. R-α-lipoic acid (ALA) inhibits protein glycation and AGEs formation while stimulating glutathione (GSH) production. Taurine mitigates oxidative stress and acts as an anti-glycation compound, preventing in vitro glycation and AGEs accumulation. This study aimed to explore the ameliorative effects of a micronutrient support (Taurine, ALA and B6: TAB) on mouse oocytes challenged with MGO. Our results indicate that MGO reduces oocyte developmental competence, while TAB supplementation improves maturation, fertilization, and blastocyst formation rates. TAB also restores cell lineage allocation, redox balance and mitigates mitochondrial dysfunction in MGO-challenged oocytes. Furthermore, cumulus cells express key enzymes in the transsulfuration pathway, and TAB enhances their mRNA expression. However, TAB does not rescue MGO-induced damage in denuded oocytes, emphasizing the supportive role of cumulus cells. Overall, these findings suggest that TAB interventions may have significant implications for addressing reproductive dysfunctions associated with elevated MGO/AGEs levels. This study highlights the potential of TAB supplementation in preserving the developmental competence of COCs exposed to MGO stress, providing insights into mitigating the impact of dicarbonyl stress on oocyte quality and reproductive outcomes.

Asunto(s)

Oocitos , Piruvaldehído , Taurina , Ácido Tióctico , Vitamina B 6 , Animales , Taurina/farmacología , Piruvaldehído/farmacología , Piruvaldehído/metabolismo , Oocitos/efectos de los fármacos , Oocitos/metabolismo , Ratones , Ácido Tióctico/farmacología , Femenino , Vitamina B 6/farmacología , Vitamina B 6/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Estrés Oxidativo/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos

RESUMEN

BACKGROUND: Multidrug resistance (MDR) is a key challenge in clinical chemotherapy. The combination of drugs can effectively reverse multi-drug resistance. OBJECTIVE: In this study, doxorubicin (DOX) was capsulated into nanoparticles formed by an amphiphilic PEGylated-poly (α-lipoic acid)-methanamide analogue of celastrol (mPEG-PαLA-CEN) prodrug polymer. CEN was linked to the branched chain of poly (α-lipoic acid) by forming ester bonds. DOX was physically trapped inside the nanoparticles via electrostatic interaction. Both drugs can be simultaneously released in response to low pH and high GSH in order to overcome DOX resistance. METHODS: The chemical structure of the mPEG-PαLA-CEN-DOX NPs was confirmed through 1H NMR, FT-IR spectroscopy, UV-Vis spectrum, DLS, and TEM. Drug-loading content, efficacy, and drug release were measured using HPLC. Cell toxicity was examined using an MTT assay. RESULTS: CEN/DOX-loaded nanoparticles were found to have spherical shapes with diameters of around 229.7 nm. The NPs exhibited high biocompatibility and released 92% DOX and 71.8% CEN in response to low pH and high GSH of tumor microenvironments. As dual drug-loaded nanoparticles, the efficacy of mPEG-PαLA-CEN-DOX NPs against tumor cell lines in vitro was enhanced for both MCF-7 and MCF-7/ADR compared to free DOX. Compared to free DOX, the IC50 of mPEG-PαLA-CEN-DOX NPs reduced from 46.10 µM to 8.36 µM for the MCF-7/ADR cell line. CONCLUSION: In conclusion, this study demonstrated that PEGylated poly (α-lipoic acid)-CEN copolymers can be used not only as biocompatible, stimulation-responsive anticancer drug nanocarriers but also as chemosensitizers to overcome multidrug resistance, which provide a theoretical base for clinical application of CEN/DOX nanodrug.

RESUMEN

Heat stress from varicocele can heighten oxidative stress in the testes, impacting sperm function and male fertility. Antioxidant therapy is explored as a remedy for varicocele, while dietary factors like processed foods, sugar, and saturated fats correlate with male infertility. Advanced glycation end products (AGEs), generated through glycation processes, can provoke oxidative stress, inflammation, and adverse health consequences. Alpha-lipoic acid (ALA), a versatile antioxidant, may alleviate oxidative stress and counteract the impact of AGEs, potentially by enhancing glucose reabsorption. Alagebrium chloride (ALT711), an anti-AGE compound, exhibits promise in cardiovascular disease by disrupting AGE cross-links. This study investigates the effects of ALA and ALT-711 on testicular function in varicocele and AGEs animal models. Both AGE and varicocele were found to alter the natural trends, leading to abnormal patterns in sperm parameters, testicular functional tests, as well as the expression of CML, RAGE, and TNF-α proteins. However, the administration of ALA or ALT711 helped mitigate these effects. While ALA demonstrated a slightly greater overall benefit compared to ALT, the difference was not statistically significant.

Asunto(s)

Productos Finales de Glicación Avanzada , Testículo , Ácido Tióctico , Varicocele , Masculino , Animales , Ácido Tióctico/farmacología , Productos Finales de Glicación Avanzada/metabolismo , Testículo/metabolismo , Testículo/efectos de los fármacos , Testículo/patología , Ratas , Varicocele/metabolismo , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Espermatozoides/efectos de los fármacos , Espermatozoides/metabolismo , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología , Antioxidantes/farmacología , Dieta , Factor de Necrosis Tumoral alfa/metabolismo , Modelos Animales de Enfermedad , Ratas Sprague-Dawley , Tiazoles

RESUMEN

Anti-estrogenic therapy is established in the management of estrogen receptor (ER)-positive breast cancer. However, to overcome resistance and improve therapeutic outcome, novel strategies are needed such as targeting widely recognized aberrant epigenetics. The study aims to investigate the combination of the aromatase inhibitor exemestane and the histone deacetylase (HDAC) inhibitor and antioxidant α-lipoic acid in ER-positive breast cancer cells. First, the enantiomers and the racemic mixture of α-lipoic acid, and rac-dihydro-lipoic acid were investigated for HDAC inhibition. We found HDAC inhibitory activity in the 1-3-digit micromolar range with a preference for HDAC6. Rac-dihydro-lipoic acid is slightly more potent than rac-α-lipoic acid. The antiproliferative IC50 value of α-lipoic acid is in the 3-digit micromolar range. Notably, the combination of exemestane and α-lipoic acid resulted in synergistic behavior under various incubation times (24 h to 10 d) and readouts (MTT, live-cell fluorescence microscopy, caspase activation) analyzed by the Chou-Talalay method. α-lipoic acid increases mitochondrial fusion and the expression of apoptosis-related proteins p21, APAF-1, BIM, FOXO1, and decreases expression of anti-apoptotic proteins survivin, BCL-2, and c-myc. In conclusion, combining exemestane with α-lipoic acid is a promising novel treatment option for ER-positive breast cancer.

Asunto(s)

Androstadienos , Antioxidantes , Apoptosis , Neoplasias de la Mama , Sinergismo Farmacológico , Inhibidores de Histona Desacetilasas , Ácido Tióctico , Humanos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Ácido Tióctico/farmacología , Femenino , Inhibidores de Histona Desacetilasas/farmacología , Androstadienos/farmacología , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Receptores de Estrógenos/metabolismo , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Células MCF-7

RESUMEN

The objective of this study was to investigate the influence of α-lipoic acid (LA; R enantiomer) supplementation on maternal and fetal metabolic health in pregnancies complicated by maternal obesity. Forty female Sprague-Dawley rats were randomized to one of 4 treatment groups (n=10/group) throughout prepregnancy (3 weeks) and gestation (20 days): (1) a low calorie control (CON); (2) a high calorie obesity-inducing diet (HC); (3) the HC diet with 0.25% LA (HC+LA) or; (4) the HC diet pair-fed to match the caloric intake of the HC+LA group (HC+PF). On gestation day 20, pregnant rats were placed under anesthesia for collection of maternal/fetal blood and tissues. Compared with the HC group, LA-supplemented mothers demonstrated lower maternal prepregnancy and gestational weight gain (GWG), improved glycemic control (lower homeostatic model assessment for insulin resistance), and higher cholesterol concentrations in serum [high-density lipoprotein cholesterol (HDL-C) and low-and very-low density lipoprotein cholesterol (LDL/VLDL) fractions] and liver. Male and female fetuses from LA-supplemented mothers exhibited lower body weight, improved insulin sensitivity, and evidence of altered lipid metabolism including lower serum HDL-C, lower serum triglyceride (TG), and increased hepatic TG accumulation. Although maternal LA supplementation showed some benefit for both mothers and fetuses with respect to obesity and glycemic control, concern about the potential longer-term implications of liver cholesterol (mothers) and TG accumulation (fetuses) needs further investigation.

RESUMEN

Parkinson's disease (PD) is an idiopathic disease caused by the loss or degeneration of the dopaminergic (dopamine-producing) neurons in the brain and characterized by various inflammatory and apoptotic responses in the neuronal cells. Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) axis is responsible for neuronal survival by providing a number of anti-inflammatory and anti-apoptotic milieu that prevent the progression of PD. Alpha-lipoic acid (ALA) is a natural cofactor that has antioxidant capacity and contributes to various metabolic processes. ALA can penetrate the blood-brain barrier and contribute to numerous neuroprotective effects. It can activate PI3K/AKT pathway with consequent reduction of different inflammatory and oxidative biomarkers. Our work aims to unfold the neuroprotective effects of ALA via targeting PI3k/AKT pathway. Forty male mice were divided into four groups: control, ALA (100 mg/kg/day; i.p.), rotenone (ROT) (1.5 mg/kg/2 days, i.p.) and rotenone + ALA for 21 days. ALA showed obvious neuroprotective effects via significant activation of PI3K/AKT pathway with subsequent decreasing level of Caspase-3. ALA resulted in prominent anti-inflammatory actions by decreasing interlukin-1ß (IL-1ß), tumor necrosis factor (TNF)-α and nuclear factor kabba (NFk)-B. ALA remarkably induced antioxidant activities via increasing reduced glutathione (GSH) and superoxide dismutase (SOD) levels as well as decreasing malondialdehyde (MDA) level. The substantial behavioral improvement reflected in these results was noticed in the ALA-treated mice as a reflection of the neuroprotective activities of ALA. In conclusion, ALA showed promising neuroprotective effects in rotenone-induced PD via activating the PI3K/AKT pathway and consequent inhibition of apoptotic and inflammatory biomarkers.

Asunto(s)

Fármacos Neuroprotectores , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Rotenona , Transducción de Señal , Ácido Tióctico , Animales , Ácido Tióctico/farmacología , Ácido Tióctico/uso terapéutico , Rotenona/toxicidad , Proteínas Proto-Oncogénicas c-akt/metabolismo , Masculino , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Ratones , Transducción de Señal/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/farmacología

RESUMEN

Alpha-lipoic acid (ALA) is a naturally occurring compound synthesized by mitochondria and widely distributed in both animal and plant tissues. It primarily influences cellular metabolism and oxidative stress networks through its antioxidant properties and is an important drug for treating metabolic diseases associated with oxidative damage. Nevertheless, research indicates that the mechanism by which ALA affects cancer cells is distinct from that observed in normal cells, exhibiting pro-oxidative properties. Therefore, this review aims to describe the main chemical and biological functions of ALA in the cancer environment, including its mechanisms and effects in tumor prevention and anticancer activity, as well as its role as an adjunctive drug in cancer therapy. We specifically focus on the interactions between ALA and various carcinogenic and anti-carcinogenic pathways and discuss ALA's pro-oxidative capabilities in the unique redox environment of cancer cells. Additionally, we elaborate on ALA's roles in nanomedicine, hypoxia-inducible factors, and cancer stem cell research, proposing hypotheses and potential explanations for currently unresolved issues.

RESUMEN

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.

RESUMEN

Background: 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. Methods: 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. Results: Our findings showed that HGA treatment significantly (P=0.0001) increased RAGE (by 140.66%), STAR (by 117.65%), 3ß-HSD (by 165.68%), and 17ß-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). Conclusion: 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.

Asunto(s)

Productos Finales de Glicación Avanzada , Células de la Granulosa , Ácido Tióctico , Humanos , Ácido Tióctico/farmacología , Ácido Tióctico/uso terapéutico , Células de la Granulosa/efectos de los fármacos , Femenino , Productos Finales de Glicación Avanzada/farmacología , Receptor para Productos Finales de Glicación Avanzada , Células Cultivadas

RESUMEN

Fresh-cut pear fruit is greatly impacted by enzymatic browning, and maintaining quality remains a challenge. This study examined the impact of exogenous α-lipoic acid (α-LA) treatment on enzymatic browning and nutritional quality of fresh-cut pears. Results revealed that 0.5 g/L α-LA treatment effectively maintained color and firmness, and inhibited the increase in microbial number. The α-LA treatment also reduced MDA and H2O2 contents, decreased PPO activity, and enhanced SOD, CAT, and PAL activities. The α-LA treatment notably upregulated phenolic metabolism-related gene expression, including PbPAL, Pb4CL, PbC4H, PbCHI and PbCHS, and then increasing total phenols and flavonoids contents. Furthermore, it also influenced carbohydrate metabolism-related gene expression, including PbSS, PbSPS, PbAI and PbNI, maintaining a high level of sucrose content. These findings indicated that α-LA treatment showed promise in reducing browning and enhancing fresh-cut pears quality, offering a potential postharvest method to prolong the lifespan and maintain nutritional quality.

Asunto(s)

Metabolismo de los Hidratos de Carbono , Frutas , Valor Nutritivo , Fenoles , Pyrus , Ácido Tióctico , Pyrus/química , Pyrus/metabolismo , Pyrus/genética , Frutas/química , Frutas/metabolismo , Frutas/efectos de los fármacos , Fenoles/metabolismo , Fenoles/análisis , Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Ácido Tióctico/metabolismo , Ácido Tióctico/farmacología , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética

RESUMEN

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-ß, Homeostasis model assessment of ß-cell function; IL-1ß, Interleukin-1ß; 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.

Asunto(s)

Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Gliclazida , Ratas Sprague-Dawley , Ácido Tióctico , Ácido Tióctico/farmacología , Ácido Tióctico/uso terapéutico , Animales , Gliclazida/farmacología , Gliclazida/uso terapéutico , Humanos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/metabolismo , Ratas , Masculino , Glucosa/metabolismo , Glucosa/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Línea Celular , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Hepatocitos/patología , Antioxidantes/farmacología , Antioxidantes/uso terapéutico

RESUMEN

The objective of this study was to examine the therapeutic efficacy of curcumin (CUR) and α-lipoic acid (ALA) in mitigating UV-A and UV-B-induced damage (UVAB) in rat dorsal skin. This was achieved through the utilisation of immunohistochemical (TUNEL), biochemical and stereological techniques. The rats in the UVAB, UVAB + CUR, and UVAB + ALA groups were subjected to UVAB irradiation for a period of two hours per day over the course of one month. The UVAB + CUR and UVAB + ALA groups were administered 100 mg/kg/day of curcumin and 100 mg/kg/day of α-lipoic acid via gavage 30 min prior to UVAB irradiation. The CUR group was administered 100 mg/kg/day of curcumin via gavage, while the ALA group received the same dose of α-lipoic acid. A significant change in the volume ratio of the dorsal skin epidermis and dermis was observed in the stereological findings of the rats in the UVAB group. These changes exhibited a favourable progression as a consequence of the CUR and ALA applications. In the UVAB group, TOS and OSI were significantly elevated as a consequence of the rise in oxidative stress. Conversely, the treatment groups demonstrated a notable reduction in TOS and OSI levels. The study also revealed a substantial increase in the number of apoptotic cells within the UVAB group. However, the treatment groups exhibited a significant decline in apoptotic cells. In conclusion, the findings suggest that CUR and ALA possess a protective effect against UVAB-induced skin damage.

RESUMEN

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.