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Fulltext The Use of Alfa-Lipoic Acid-R (ALA-R) in Patients with Mild-Moderate Carpal Tunnel Syndrome: A Randomised Controlled Open Label Prospective Study

Passiatore M, Perna A, De-Vitis R, Taccardo G

Malays Orthop J, 2020 Mar;14(1):1-6.
PMID: 32296475 DOI: 10.5704/MOJ.2003.001

Introduction: Carpal tunnel syndrome is one of the most common peripheral neuropathies. Only a few studies evaluate the efficacy of "nutraceuticals" on peripheral nerves and neuropathic pain. The aim of the present investigation is to evaluate the role of Alfa-Lipoic Acid-R (ALA-R) on clinical and functional outcomes in patients affected by mild to moderate carpal tunnel syndrome.
Material and Methods: The present investigation is a prospective randomised controlled open label study, performed at our Hand Surgery Department (Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome) from October 2018 to March 2019. The enrolled patients were divided in two groups: Group A (ALA-R 600mg once day for 60 days) and Group B (control Group, no drug administration).
Results: 134 patients (74 F, 60 M) met the inclusion and exclusion criteria. In Group A, there was a statistically significant pain reduction compared to the control Group. Using the Boston Carpal Tunnel Questionnaire, there were no significant improvements in the other symptoms and function.
Conclusion: ALA-R full dose administration for two months leads to positive short term results in terms of symptoms and function improvement, even if the surgical carpal tunnel release remains the treatment of choice.

Matched MeSH terms: Thioctic Acid
Alpha lipoic acid possess dual antioxidant and lipid lowering properties in atherosclerotic-induced New Zealand White rabbit

Zulkhairi A, Zaiton Z, Jamaluddin M, Sharida F, Mohd TH, Hasnah B, et al.

Biomed Pharmacother, 2008 Dec;62(10):716-22.
PMID: 18538528 DOI: 10.1016/j.biopha.2006.12.003

There is accumulating data demonstrated hypercholesterolemia and oxidative stress play an important role in the development of atherosclerosis. In the present study, a protective activity of alpha-lipoic acid; a metabolic antioxidant in hypercholesterolemic-induced animals was investigated. Eighteen adult male New Zealand White (NZW) rabbit were segregated into three groups labelled as group K, AT and ALA (n=6). While group K was fed with normal chow and acted as a control, the rest fed with 100 g/head/day with 1% high cholesterol diet to induce hypercholesterolemia. 4.2 mg/body weight of alpha lipoic acid was supplemented daily to the ALA group. Drinking water was given ad-libitum. The study was designed for 10 weeks. Blood sampling was taken from the ear lobe vein at the beginning of the study, week 5 and week 10 and plasma was prepared for lipid profile estimation and microsomal lipid peroxidation index indicated with malondialdehyde (MDA) formation. Animals were sacrificed at the end of the study and the aortas were excised for intimal lesion analysis. The results showed a significant reduction of lipid peroxidation index indicated with low MDA level (p<0.05) in ALA group compared to that of the AT group. The blood total cholesterol (TCHOL) and low density lipoprotein (LDL) levels were found to be significantly low in ALA group compared to that of the AT group (p<0.05). Histomorphometric intimal lesion analysis of the aorta showing less of atheromatous plaque formation in alpha lipoic acid supplemented group (p<0.05) compared to that of AT group. These findings suggested that apart from its antioxidant activity, alpha lipoic acid may also posses a lipid lowering effect indicated with low plasma TCHOL and LDL levels and reduced the athero-lesion formation in rabbits fed a high cholesterol diet.

Matched MeSH terms: Thioctic Acid/pharmacology*; Thioctic Acid/therapeutic use
A study of the antioxidant effect of alpha lipoic acids on sperm quality

Ibrahim SF, Osman K, Das S, Othman AM, Majid NA, Rahman MP

Clinics (Sao Paulo), 2008 Aug;63(4):545-50.
PMID: 18719769

OBJECTIVE: Assisted reproductive techniques are useful in helping infertile couples achieve successful conception. Initial studies have shown that sperm cryopreservation, one step in assisted reproduction, causes a dramatic reduction in sperm quality. This has been attributed to, among other things, free radical activities. The aim of the present study was to minimize this oxidative attack by adding an antioxidant into the sperm microenvironment. Alpha lipoic acids were selected for this purpose for their efficient free radical scavenging properties and solubility in lipid and aqueous phases.
METHODS: For this investigation, semen from six Boer bucks was pooled. Seminal analysis of the baseline prior to incubation of samples with different concentrations of Alpha lipoic acids (0.00625, 0.0125, 0.025, 0.05, 0.1 mmol/ml) was performed, and post-seminal analysis was conducted after a one-hour incubation. The comet assay was used to observe the effect of Alpha lipoic acids on sperm DNA integrity. Statistical analysis using an unpaired t-test with a significance level of p<0.05 was then performed.
RESULTS: Our results indicate that the sperm motility rate was improved after incubation with Alpha lipoic acids at a concentration of 0.02 mmol/ml. This concentration was also capable of reducing DNA damage.
CONCLUSION: In conclusion, Alpha lipoic acids renders cryoprotection to sperm, thereby improving sperm quality.

Matched MeSH terms: Thioctic Acid/therapeutic use*
Fulltext (R)-(+)-α-lipoic acid protected NG108-15 cells against H₂O₂-induced cell death through PI3K-Akt/GSK-3β pathway and suppression of NF-κβ-cytokines

Kamarudin MN, Mohd Raflee NA, Hussein SS, Lo JY, Supriady H, Abdul Kadir H

Drug Des Devel Ther, 2014;8:1765-80.
PMID: 25336920 DOI: 10.2147/DDDT.S67980

Alpha-lipoic acid, a potent antioxidant with multifarious pharmacological benefits has been reported to be neuroprotective in several neuronal models and used to treat neurological disorders such as Alzheimer's disease. Nonetheless, conclusive mechanisms of alpha-lipoic acid for its protective effects particularly in NG108-15 cells have never been investigated. In this study, the intricate neuroprotective molecular mechanisms by (R)-(+)-alpha-lipoic acid (R-LA) against H2O2-induced cell death in an in vitro model of neurodegeneration were elucidated. Pretreatment with R-LA (2 hours) significantly increased NG108-15 cell viability as compared to H2O2-treated cells and mitigated the induction of apoptosis as evidenced by Hoechst 33342/propidium iodide staining. R-LA (12.5-50 μM) aggrandized the reduced glutathione over glutathione disulfide ratio followed by a reduction in the intracellular reactive oxygen species level and an increase in mitochondrial membrane potential following H2O2 exposure. Moreover, pretreatment with R-LA stimulated the activation of PI3K-Akt through mTORC1 and mTORC2 components (mTOR, rictor and raptor) and production of antiinflammatory cytokine, IL-10 which led to the inactivation of glycogen synthase kinase-3β (GSK-3β) and reduction of both Bax/Bcl2 and Bax/Bcl-xL ratios, accompanied by inhibition of the cleaved caspase-3. Additionally, this observation was preceded by the suppression of NF-κβ p65 translocation and production of proinflammatory cytokines (IL-6 and TNF-α). The current findings accentuate new mechanistic insight of R-LA against apoptogenic and brain inflammatory factors in a neuronal model. These results further advocate the therapeutic potential of R-LA for the treatment of neurodegenerative diseases.

Matched MeSH terms: Thioctic Acid/pharmacology*; Thioctic Acid/chemistry
Fulltext Neuroprotective effects of alpha lipoic Acid on haloperidol-induced oxidative stress in the rat brain

Perera J, Tan JH, Jeevathayaparan S, Chakravarthi S, Haleagrahara N

Cell Biosci, 2011;1(1):12.
PMID: 21711768 DOI: 10.1186/2045-3701-1-12

Haloperidol is an antipsychotic drug that exerts its' antipsychotic effects by inhibiting dopaminergic neurons. Although the exact pathophysiology of haloperidol extrapyramidal symptoms are not known, the role of reactive oxygen species in inducing oxidative stress has been proposed as one of the mechanisms of prolonged haloperidol-induced neurotoxicity. In the present study, we evaluate the protective effect of alpha lipoic acid against haloperidol-induced oxidative stress in the rat brain. Sprague Dawley rats were divided into control, alpha lipoic acid alone (100 mg/kg p.o for 21 days), haloperidol alone (2 mg/kg i.p for 21 days), and haloperidol with alpha lipoic acid groups (for 21 days). Haloperidol treatment significantly decreased levels of the brain antioxidant enzymes super oxide dismutase and glutathione peroxidase and concurrent treatment with alpha lipoic acid significantly reversed the oxidative effects of haloperidol. Histopathological changes revealed significant haloperidol-induced damage in the cerebral cortex, internal capsule, and substantia nigra. Alpha lipoic acid significantly reduced this damage and there were very little neuronal atrophy. Areas of angiogenesis were also seen in the alpha lipoic acid-treated group. In conclusion, the study proves that alpha lipoic acid treatment significantly reduces haloperidol-induced neuronal damage.

Matched MeSH terms: Thioctic Acid
Effect of alpha lipoic acid on oxidative stress and vascular wall of diabetic rats

Balkis Budin S, Othman F, Louis SR, Abu Bakar M, Radzi M, Osman K, et al.

Rom J Morphol Embryol, 2009;50(1):23-30.
PMID: 19221642

PREMISES AND OBJECTIVES: Antioxidant plays an important role in preventing the progression of diabetes mellitus (DM) complications. The aim of the present study was to investigate the effect of alpha lipoic acid (ALA) supplementation on plasma lipid, oxidative stress and vascular changes in diabetic rats.

Matched MeSH terms: Thioctic Acid/pharmacology*
Fulltext Induction of Caspase-Mediated Apoptosis in HepG2 Liver Carcinoma Cells Using Mutagen-Antioxidant Conjugated Self-Assembled Novel Carbazole Nanoparticles and In Silico Modeling Studies

Anand K, Abdul NS, Ghazi T, Ramesh M, Gupta G, Tambuwala MM, et al.

ACS Omega, 2021 Jan 12;6(1):265-277.
PMID: 33458478 DOI: 10.1021/acsomega.0c04461

In this study, novel self-assembled carbazole-thiooctanoic acid nanoparticles (CTNs) were synthesized from amino carbazole (a mutagen) and thiooctanoic acid (an antioxidant). The nanoparticles were characterized using hyperspectral techniques. Then, the antiproliferative potential of CTNs was determined in HepG2 liver carcinoma cells. This study employed a solvent-antisolvent interaction method to synthesize a spherical CTN of size less than 50 nm. Moreover, CT was subsequently capped to gold nanoparticles (AuNPs) in the additional comparative studies. The CT derivative was synthesized from carbazole and lipoic acid by the amide bond formation reaction using a coupling agent. Furthermore, it was characterized using infrared (IR), 1H nuclear magnetic resonance, dynamic light scattering (DLS), and transmission electron microscopy techniques. The CT-capped gold nanoparticles (CTAuNPs) were prepared from CT, chloroauric acid, and NaBH4. The CTAuNPs were characterized using ultraviolet-visible, high-resolution TEM, DLS, and Fourier transform IR techniques. The cytotoxicity and apoptosis-inducing ability of both nanoparticles were determined in HepG2 cells. The results demonstrate that CTNs exhibit antiproliferative activity in the cancerous HepG2 cells. Moreover, molecular docking and molecular dynamics studies were conducted to explore the therapeutic potential of CT against human EGFR suppressor protein to gain more insights into the binding mode of the CT, which may show a significant role in anticancer therapy.

Matched MeSH terms: Thioctic Acid