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Molecules (Basel, Switzerland) Jan 2023The influence of kaempferol (K), myricetin (M) and lipoic acid (LA) on the properties of natural erythrocytes, isolated from animal blood and biological membrane models...
The influence of kaempferol (K), myricetin (M) and lipoic acid (LA) on the properties of natural erythrocytes, isolated from animal blood and biological membrane models (monolayers and liposomes) made of phosphatidylcholine (PC), cholesterol (CHOL), and sphingomyelin (SM), CHOL in a ratio of 10:9, was investigated. The Langmuir method, Brewster angle microscopy (BAM) and microelectrophoresis were used. The presented results showed that modification of liposomes with kaempferol, myricetin and lipoic acid caused changes in the surface charge density and the isoelectric point value. Comparing the tested systems, several conclusions were made. (1) The isoelectric point for the DPPC:Chol:M (~2.2) had lower pH values compared to lipoic acid (pH~2.5) and kaempferol (pH~2.6). (2) The isoelectric point for the SM-Chol with myricetin (~3.0) had lower pH values compared to kaempferol (pH~3.4) and lipoic acid (pH~4.7). (3) The surface charge density values for the DPPC:Chol:M system in the range of pH 2-9 showed values from 0.2 to -2.5 × 10 C m. Meanwhile, for the DPPC:Chol:K and DPPC:Chol:LA systems, these values were higher at pH~2 (0.7 × 10 C m and 0.8 × 10 C m) and lower at pH~9 (-2.1 × 10 C m and -1.8 × 10 C m), respectively. (4) The surface charge density values for the SM:Chol:M system in the range of pH 2-9 showed values from 0.5 to -2.3 × 10 C m. Meanwhile, for the DPPC:Chol:K and DPPC:Chol:LA systems, these values were higher at pH~2 (0.8 × 10 C m), and lower at pH~9 (-1.0 × 10 C m and -1.8 × 10 C m), respectively. (5) The surface charge density values for the erythrocytes with myricetin in the range of pH 2-9 showed values from 1.0 to -1.8 × 10 C m. Meanwhile, for the erythrocytes:K and erythrocytes:LA systems, these values, at pH~2, were 1.3 × 10 C m and 0.8 × 10 C m and, at pH~9, -1.7 × 10 C m and -1.0 × 10 C m, respectively.
Topics: Animals; Liposomes; Kaempferols; Thioctic Acid; Sphingomyelins; Cholesterol; Lecithins; Cell Membrane; 1,2-Dipalmitoylphosphatidylcholine
PubMed: 36770679
DOI: 10.3390/molecules28031013 -
Diabetes & Metabolism Journal Dec 2020
Topics: Animals; Diabetes Mellitus, Experimental; Diet, High-Fat; Metformin; Peripheral Nerves; Pharmaceutical Preparations; Rats; Streptozocin; Thioctic Acid
PubMed: 33389958
DOI: 10.4093/dmj.2020.0252 -
European Review For Medical and... Jul 2018Cancer patients frequently experience Chemotherapy-Induced Peripheral Neuropathy (CIPN), as a typical side effect related to time of administration and dose of... (Review)
Review
OBJECTIVE
Cancer patients frequently experience Chemotherapy-Induced Peripheral Neuropathy (CIPN), as a typical side effect related to time of administration and dose of anticancer agents. Yet, CIPN pathophysiology is poorly understood, and there is a lack of well-tolerated pharmacological remedies helpful to prevent or treat it. Therefore, new safe and effective compounds are highly warranted, namely if based on an adequate understanding of the pathogenic mechanisms.
MATERIAL AND METHODS
Herein we reviewed and discussed scientific data related to the beneficial role of some non-conventional treatments able to counteract CIPN, focusing our attention on alpha-lipoic acid (ALA) and L-acetyl-carnitine (LAC), two natural products that have been demonstrated to be promising preventive drugs.
RESULTS
Although a growing body of in vitro and in vivo studies support ALA as a molecule able to counteract CIPN symptoms, mostly due to its antioxidant and anti-inflammatory properties, only two randomized clinical trials evaluated ALA usefulness in preventing chemotherapy-related neuropathy. Unfortunately, these studies were inconclusive and clinical outcomes showed to be highly dependent on the route of administration (oral versus or intravenous injection). LAC has demonstrated beneficial effects on both in vitro and in animal studies. Yet, some controversies aroused from randomized clinical trials. Indeed, while CIPN-patients treated with Taxane showed no benefit from LAC treatment, CIPN-patients treated with platinum compounds exhibit significant improvement of CIPN-related symptoms. Therefore, LAC treatment should be used, and thoroughly investigated only in patients treated with chemotherapy protocols Taxanes-free.
CONCLUSIONS
Mechanisms of toxicity triggered by each single drug need to be deeply explored to better identify effective compounds to prevent or treat them. Moreover, additional experiments are mandatory to establish effective doses and length of treatment for each clinical situation in order to perform large and long-term randomized studies.
Topics: Acetylcarnitine; Animals; Antineoplastic Agents; Biological Products; Humans; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic; Thioctic Acid
PubMed: 30058711
DOI: 10.26355/eurrev_201807_15534 -
Kidney International Dec 2021Lipoic acid (alpha lipoic acid, thioctic acid) is a popular over-the-counter antioxidant and insulin-mimetic supplement under investigation in a variety of conditions... (Clinical Trial)
Clinical Trial
Lipoic acid (alpha lipoic acid, thioctic acid) is a popular over-the-counter antioxidant and insulin-mimetic supplement under investigation in a variety of conditions including multiple sclerosis, diabetes, and schizophrenia. Unfortunately, high-grade proteinuria was an unexpected adverse event specific to the treatment arm of our clinical trial investigating lipoic acid supplementation in patients with multiple sclerosis. This observation led to detection of similar patients in our nephrology practice. Here, we describe four biopsy-proven cases of neural epidermal growth factor-like 1 (NELL1)-associated membranous nephropathy following lipoic acid supplementation and a fifth suspected case. Discontinuation of lipoic acid and supportive therapy resulted in remission.
Topics: Calcium-Binding Proteins; Dietary Supplements; EGF Family of Proteins; Glomerulonephritis, Membranous; Humans; Proteinuria; Thioctic Acid
PubMed: 34662650
DOI: 10.1016/j.kint.2021.10.010 -
Oxidative Medicine and Cellular... 2021-Lipoic acid (ALA) is widely used as a nutritional supplement and therapeutic agent in diabetes management. Well-established antioxidant and hypoglycemic effects of ALA...
-Lipoic acid (ALA) is widely used as a nutritional supplement and therapeutic agent in diabetes management. Well-established antioxidant and hypoglycemic effects of ALA were considered to be particularly important in combating diabetic complications including renal injury. The present study evaluated the potential of ALA to affect profibrotic events in kidney that could alter its structure and functioning. ALA was administered intraperitoneally (10 mg/kg) to nondiabetic and streptozotocin-induced diabetic male Wistar rats for 4 and 8 weeks. The effects of ALA were assessed starting from structural/morphological alterations through changes that characterize profibrotic processes, to regulation of collagen gene expression in kidney. Here, we demonstrated that ALA improved systemic glucose and urea level, reduced formation of renal advanced glycation end products (AGEs), and maintained renal structural integrity in diabetic rats. However, profibrotic events provoked in diabetes were not alleviated by ALA since collagen synthesis/deposition and expression of transforming growth factor-1 (TGF-1) and -smooth muscle actin (-SMA) remained elevated in ALA-treated diabetic rats, especially after 8 weeks of diabetes onset. Moreover, 8 weeks treatment of nondiabetic rats with ALA led to the development of profibrotic features reflected in increased collagen synthesis/deposition. Besides the TGF-1 downstream signaling, the additional mechanism underlying the upregulation of collagen IV in nondiabetic rats treated with ALA involves decreased DNA methylation of its promoter that could arise from increased Tet1 expression. These findings emphasize the therapeutic caution in the use of ALA, especially in patients with renal diabetic complication.
Topics: Animals; Collagen; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Kidney; Male; Rats; Rats, Wistar; Thioctic Acid
PubMed: 33777319
DOI: 10.1155/2021/6669352 -
International Journal of Molecular... Dec 2022Dapsone (DDS) therapy can frequently lead to hematological side effects, such as methemoglobinemia and DNA damage. In this study, we aim to evaluate the protective...
Dapsone (DDS) therapy can frequently lead to hematological side effects, such as methemoglobinemia and DNA damage. In this study, we aim to evaluate the protective effect of racemic alpha lipoic acid (ALA) and its enantiomers on methemoglobin induction. The pre- and post-treatment of erythrocytes with ALA, ALA isomers, or MB (methylene blue), and treatment with DDS-NOH (apsone hydroxylamine) was performed to assess the protective and inhibiting effect on methemoglobin (MetHb) formation. Methemoglobin percentage and DNA damage caused by dapsone and its metabolites were also determined by the comet assay. We also evaluated oxidative parameters such as SOD, GSH, TEAC (Trolox equivalent antioxidant capacity) and MDA (malondialdehyde). In pretreatment, ALA showed the best protector effect in 2.5 µg/mL of DDS-NOH. ALA (1000 µM) was able to inhibit the induced MetHb formation even at the highest concentrations of DDS-NOH. All ALA tested concentrations (100 and 1000 µM) were able to inhibit ROS and CAT activity, and induced increases in GSH production. ALA also showed an effect on DNA damage induced by DDS-NOH (2.5 µg/mL). Both isomers were able to inhibit MetHb formation and the S-ALA was able to elevate GSH levels by stimulating the production of this antioxidant. In post-treatment with the R-ALA, this enantiomer inhibited MetHb formation and increased GSH levels. The pretreatment with R-ALA or S-ALA prevented the increase in SOD and decrease in TEAC, while R-ALA decreased the levels of MDA; and this pretreatment with R-ALA or S-ALA showed the effect of ALA enantiomers on DNA damage. These data show that ALA can be used in future therapies in patients who use dapsone chronically, including leprosy patients.
Topics: Methemoglobin; Antioxidants; Thioctic Acid; Dapsone; Superoxide Dismutase; DNA Damage
PubMed: 36613503
DOI: 10.3390/ijms24010057 -
Drug Delivery Dec 2022The current work aims to design thioctic acid (TA) and glatiramer acetate (GA) nanoconjugate (thioctamer) loaded hydrogel formula as well as evaluation of thioctamer...
The current work aims to design thioctic acid (TA) and glatiramer acetate (GA) nanoconjugate (thioctamer) loaded hydrogel formula as well as evaluation of thioctamer preclinical efficacy in expediting wound healing in a rat model of the diabetic wound. Thioctamer was prepared by conjugation of GA and TA in a 1:1 molar ratio. Particle size, zeta potential, and thermodynamic stability of the prepared thioctamer were assessed. Thioctamer was loaded in hydroxypropyl methylcellulose-based hydrogel and release study was investigated. The ability of thioctamer to enhance the process of wound healing in diabetic rats was investigated by assessing wound contraction and immunohistochemical assessment of the inflammation markers IL-6 and TNF-α. The results demonstrated that thioctamer showed particle size of 137 ± 21.4 nm, polydispersity index (PDI) of 0.235, and positive zeta potential value of 7.43 ± 4.95 mV. On day 7 of making a skin excision, diabetic rat wounds administered thioctamer preparation showed almost complete healing (95.6 ± 8.6%). Meanwhile, % of wound contraction in animals treated with TA or GA groups exhibited values amounting to 56.5 ± 5.8% and 62.6 ± 7.1%, respectively. Histological investigation showed that the highest healing rate was noted in the thioctamer group animals, as the surface of the wound was nearly fully protected by regenerated epithelium with keratinization, with few inflammatory cells noticed. Thioctamer significantly (<.05) inhibited IL-6 and TNF-α expression as compared with sections obtained from the negative control, TA, GA, or positive control group animals on day 7. The evidence of the ability of thioctamer to significantly expedite wound healing in the diabetic rats is presented.
Topics: Animals; Diabetes Mellitus, Experimental; Glatiramer Acetate; Hydrogels; Interleukin-6; Nanoconjugates; Rats; Thioctic Acid; Tumor Necrosis Factor-alpha; Wound Healing
PubMed: 35642489
DOI: 10.1080/10717544.2022.2081382 -
Medicina (Kaunas, Lithuania) May 2019Ascorbic acid, alpha lipoic acid (ALA) and silymarin are well-known antioxidants that have hepatoprotective effects. This study aims to investigate the effects of these...
Ascorbic acid, alpha lipoic acid (ALA) and silymarin are well-known antioxidants that have hepatoprotective effects. This study aims to investigate the effects of these three compounds combined with attenuating drug-induced oxidative stress and cellular damage, taking acetaminophen (APAP)-induced toxicity in rats as a model both in vivo and in vitro. Freshly cultured primary rat hepatocytes were treated with ascorbic acid, ALA, silymarin and their combination, both with and without the addition of APAP to evaluate their in vitro impact on cell proliferation and mitochondrial activity. In vivo study was performed on rats supplemented with the test compounds or their combination for one week followed by two toxic doses of APAP. Selected liver function tests and oxidative stress markers including superoxide dismutase (SOD), malondialdehyde (MDA) and oxidized glutathione (GSSG) were detected. The in vivo results showed that all three pretreatment compounds and their combination prevented elevation of SOD and GSSG serum levels indicating a diminished burden of oxidative stress. Moreover, ascorbic acid, ALA and silymarin in combination reduced serum levels of liver enzymes; however, silymarin markedly maintained levels of all parameters to normal ranges. Silymarin either alone or combined with ascorbic acid and ALA protected cultured rat hepatocytes and increased cellular metabolic activity. The subjected agents were capable of significantly inhibiting the presence of oxidative stress induced by APAP toxicity and the best result for protection was seen with the use of silymarin. The measured liver function tests may suggest an augmented hepatoprotection of the combination preparation than when compared individually.
Topics: Acetaminophen; Animals; Ascorbic Acid; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Male; Oxidative Stress; Protective Factors; Rats; Rats, Sprague-Dawley; Silymarin; Thioctic Acid
PubMed: 31117289
DOI: 10.3390/medicina55050181 -
Obesity Reviews : An Official Journal... May 2017Obesity is associated with significant morbidity and mortality rates. Even modest weight loss may be associated with health benefits. Alpha-lipoic acid (ALA) is a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Obesity is associated with significant morbidity and mortality rates. Even modest weight loss may be associated with health benefits. Alpha-lipoic acid (ALA) is a naturally occurring antioxidant. Studies have suggested anti-obesity properties of ALA; however, results are inconsistent. The purpose of this study is to conduct a meta-analysis of the effect of ALA on weight and body mass index (BMI).
METHODS
A comprehensive, systematic literature search identified 10 articles on randomized, double-blind, placebo-controlled studies involving ALA. We conducted a meta-analysis of mean weight and BMI change differences between ALA and placebo treatment groups.
RESULTS
Alpha-lipoic acid treatment coincided with a statistically significant 1.27 kg (confidence interval = 0.25 to 2.29) greater mean weight loss compared with the placebo group. A significant overall mean BMI difference of -0.43 kg/ m (confidence interval = -0.82 to -0.03) was found between the ALA and placebo groups. Meta-regression analysis showed no significance in ALA dose on BMI and weight changes. Study duration significantly affected BMI change, but not weight change.
CONCLUSIONS
Alpha-lipoic acid treatment showed small, yet significant short-term weight loss compared with placebo. Further research is needed to examine the effect of different doses and the long-term benefits of ALA on weight management.
Topics: Antioxidants; Body Mass Index; Dietary Supplements; Humans; Randomized Controlled Trials as Topic; Thioctic Acid; Weight Loss
PubMed: 28295905
DOI: 10.1111/obr.12528 -
Archives of Biochemistry and Biophysics Dec 2023Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver disorder affecting a significant part of the global population. This study aimed to...
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver disorder affecting a significant part of the global population. This study aimed to investigate the potential therapeutic effects of α-lipoic acid (α-LA) on the inflammatory response during simple steatosis development and progression into steatohepatitis. The study used the MASLD model in male Wistar rats that were fed a standard diet or a high-fat diet (HFD) for 8 weeks. Throughout the entire experiment, half of the animals received α-LA supplementation. The hepatic activity of pro-inflammatory n-6 and anti-inflammatory n-3 polyunsaturated fatty acid (PUFA) pathways and the concentration of arachidonic acid (AA) in selected lipid fractions were determined by the gas-liquid chromatography (GLC). The hepatic expression of proteins from inflammatory pathway was measured by the Western blot technique. The level of eicosanoids, cytokines and chemokines was assessed by the ELISA or multiplex assay kits. The results showed that α-LA supplementation attenuated the activity of n-6 PUFA pathway in FFA and DAG and increased the activity of n-3 PUFA pathway in PL, TAG and DAG. In addition, the administration of α-LA decreased the concentration of AA in DAG and FFA, indicating its potential protective effect on the deterioration of simple hepatic steatosis. The supplementation of α-LA also increased the expression of COX-1 and COX-2 with the lack of significant changes in prostaglandins profile. We observed an increase in the expression of 12/15-LOX, which was reflected in an increase in lipoxin A4 (LXA4) level. A decrease in pro-inflammatory cytokines and an increase in anti-inflammatory cytokines was also noticed in the liver of rats treated with HFD and α-LA. Our observations confirm that α-LA treatment has potential protective effects on inflammation development in the MASLD model. We believe that α-LA has a preventive impact when it comes to the progression of simple steatosis lesions to steatohepatitis.
Topics: Rats; Male; Animals; Thioctic Acid; Diet, High-Fat; Rats, Wistar; Fatty Liver; Liver; Inflammation; Anti-Inflammatory Agents; Cytokines
PubMed: 37926405
DOI: 10.1016/j.abb.2023.109811