Effects Of Antioxidant Alpha-lipoic Acid Research Articles

Effect of alpha-lipoic acid on oxidative stress parameters: A systematic review and meta-analysis

• Alpha-lipoic acid (ALA) has been recognized as a strong dietary antioxidant. • ALA consumption significantly decreased Malondialdehyde (MDA). • ALA supplementation is a good choice to control lipid peroxidation. The antioxidant effect of alpha-lipoic acid (ALA) and its effect in reducing reactive oxygen species has been demonstrated in primary studies. This systematic review and meta-analysis was conducted to evaluate the impact of alpha-lipoic acid (ALA) supplementation on oxidative stress (OS) parameters. We performed a comprehensive search in major electronic databases. A random-effects model was used to pool data and calculated standard mean difference and 95% confidence intervals. Fifteen studies were included in the meta-analyses. The outcomes of this meta-analysis indicated that ALA consumption significantly decreased Malondialdehyde (MDA) levels compare to control group. We found no significant effect of ALA supplementation on other antioxidant enzymes and oxidative stress parameters. Overall, the present meta-analysis indicated that ALA supplementation might lead to an amelioration in lipid peroxidation. It can be recommended that the use of ALA supplementation in < 800 mg/day is a good choice to control lipid peroxidation.

Elasticity Changes in the Crystalline Lens during Oxidative Damage and the Antioxidant Effect of Alpha-Lipoic Acid Measured by Optical Coherence Elastography

Age-related cataracts are one of the most prevalent causes of visual impairment around the world. Understanding the mechanisms of cataract development and progression is essential to enable early clinical diagnosis and treatment to preserve visual acuity. Reductive chemicals are potential medicines effective on cataract treatment. In this work, we investigated the cataract-induced oxidative damage in the crystalline lens and a kind of reductant, α-lipoic acid (ALA), ability to reduce the damage. We created oxidative environment to investigate the relationship between the progression of oxidative cataract and lenticular biomechanical properties measured by dynamic optical coherence elastography in porcine crystalline lenses ex vivo. The efficacy of ALA to minimize the stiffening of the lens was also quantified. The results showed a significant increase in Young’s modulus of the lens due to the formation of the oxidative cataract. We found a statistically significant difference between Young’s modulus of the lenses stored in phosphate-buffered saline and ALA solution after incubation in H2O2 solution for 3 h (43.0 ± 9.0 kPa versus 20.7 ± 3.5 kPa, respectively). These results show that the lens stiffness increases during oxidative cataract formation, and ALA has the potential to reverse stiffening of the lens caused by oxidative damage.

Антиоксидантные эффекты альфа-липоевой кислоты и перспектива ее применения в терапии диабетической автономной невропатии

Антиоксидантные эффекты альфа-липоевой кислоты и перспектива ее применения в терапии диабетической автономной невропатии

Роль и место нарушенного окислительно- восстановительного баланса в развитии диабетической невропатии и антиоксидантные эффекты альфа-липоевой кислоты

Роль и место нарушенного окислительно- восстановительного баланса в развитии диабетической невропатии и антиоксидантные эффекты альфа-липоевой кислоты

Apoptotic events induced by high glucose in human hepatoma HepG2 cells involve endoplasmic reticulum stress and MAPK's activation.

To investigate whether endoplasmic reticulum (ER) stress participates in the induction of apoptosis in HepG2 cells exposed to high glucose and explore its probable mechanism. A series of experiments were performed following HepG2 cells treated with different concentrations of glucose for 48h. The apoptosis was detected by means of Hoechst staining and flow cytometry. Caspase-3 activity assay was performed by measuring the pNA (p-nitroaniline) to indirectly reveal the catalytic activity of caspase-3. The expression levels of apoptosis-, ER stress-associated proteins and MAPKs were analyzed by western blot. To further characterize the molecular mechanisms, the effects of antioxidant alpha-lipoic acid (ALA) and specific inhibitors for JNK and p38 (SP600125 and SB203580, respectively) were examined by Hoechst staining, immunofluorescence, and western blot. After HepG2 cells were incubated with high glucose for 48h, both Hoechst staining and flow cytometry analyses unveiled the apoptosis of HepG2 cells. Caspase-3 activity assay revealed that the activity of caspase-3 was enhanced. Western blot showed an enhancement of pro-caspase-9 degradation, a reduction of Bcl-2/Bax ratio, a decrease in GRP78 expression, and increases in CHOP and p47/phox levels. In addition, western blot analysis presented that phosphorylation of p38 and JNK was triggered and that the expression of ASK1 was elevated. In the case of the contributions of oxidative stress and the MAPK signaling pathways, all ALA, SP600125 and SB203580 were able to largely rescue high glucose-induced apoptosis. High glucose induced the apoptosis in HepG2 cells through the activation of ASK1-p38/JNK pathway mediated by ER stress and oxidative stress.

Abstract 1498: Alpha-Lipoic acid suppresses migration and invasiveness of thyroid cancer cells through inhibition of epithelial-mesenchymal transition .

Abstract Reactive oxygen species (ROS) are recently known as a contributor to tumor progression and metastasis through several mechanisms including induction of epithelial-mesenchymal transition (EMT), invasion, and tumor angiogenesis. In this study, we investigated the role of alpha-Lipoic acid (ALA), a potential antioxidant, on EMT in thyroid cancer cell lines. Human thyroid cancer-derived cell lines, BCPAP (BRAF V600E), HTH83 (HRAS Q61R), CAL62 (KRAS G12R), BHT101 (BRAF V600E), and FTC133 (PTEN null) were treated with ALA, and changes in ROS generation were measured by DCFH-DA. The expression of E-cadherin, vimentin and Twist were determined by immunoblot analysis. Cell migration and invasion were evaluated by scratch assay and by Boyden chamber assay. ALA significantly decreased intracellular ROS generation in most cell lines. The total amount of E-cadherin increased and those of vimentin and Twist decreased after ALA treatment in 4 thyroid cancer cell lines (BCPAP, HTH83, BHT101 and CAL62) in a dose-dependent manner (0.2∼1.0 mM). But, the changes in E-cadherin, vimentin and Twist were opposite in FTC133 cells. The cell migration and invasion ability decreased after treatment with ALA in all cell lines except FTC133 (PTEN null cell). These results suggest that ALA is a potential agent to inhibit EMT resulting in suppression of migration and of invasiveness in thyroid cancer cell lines with RAS or BRAF mutation, probably through reducing cellular amount of Twist. We suggest that it might be caused by antioxidant effects of ALA, but the exact mechanism of action of ALA is not clear yet. ALA could be a novel, potential agent to suppress metastasis of tumors in patients with thyroid cancer. Citation Format: Ji Min Han, Hyun-Jeung Choi, Ji Hye Yim, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Eui Young Kim, Won Bae Kim. Alpha-Lipoic acid suppresses migration and invasiveness of thyroid cancer cells through inhibition of epithelial-mesenchymal transition . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1498. doi:10.1158/1538-7445.AM2013-1498

The Effect of Alpha-lipoic Acid on the Cell Cycle Arrest and Apoptosis in Rat Vascular Smooth Muscle Cells

Background: The proliferation of vascular smooth muscle cells (VSMCs) is a hallmark of atheroscelrosis and post-angioplasty restenosis. We previously showed that alpha-lipoic acid (ALA) inhibited neointimal hyperplasia and has potential anti-atherosclerosis effect in rat carotid artery balloon injured model. Here, we investigated whether alpha-lipoic acid inhibited proliferation of cells and induced apoptosis in rat vascular smooth muscle cells. Methods: VSMCs were treated with ALA under each condition, harvested and protein was extracted. Same amount of protein was loaded into SDS-PAGE and western blot analysis was performed with various cell cycle regulation protein. To examine ALA induce apoptosis in VSMCs, FACS and DNA fragmentation assay were performed. Antioxidant effect of ALA was determined by DCF-DA staining. Results: ALA induced VSMCs cell cycle arrest and induced p21, p27 and p53 proteins. Also ALA induced PTEN expression and AMPK phosphorylation. Increased AMPK phosphorylation reduced Erk-2 phosphorylation and finally arrested cell cycle promotion. The apoptotic effect was also shown by ALA treatment. Also we confirmed that ALA reduced ROS generation in VSMCs. Conclusion: The present data suggest that ALA has anti-proliferative effect and arrests cell proliferation. Therefore, ALA may provide new strategies for the prevention of neointimal hyperplasia after angioplasty. (J Kor Diabetes Assoc 31:200~207, 2007)

Heme oxygenase-1 contributes to the cytoprotection of alpha-lipoic acid via activation of p44/42 mitogen-activated protein kinase in vascular smooth muscle cells

Alpha-lipoic acid (ALA) is a natural antioxidant that scavenges reactive oxygen species (ROS) and regenerates or recycles endogenous antioxidants. ALA has recently been reported to protect against oxidative injury in various disease processes. The aim of this study was to investigate whether the antioxidant effect of ALA is mediated by the induction of heme oxygenase (HO)-1 in rat aortic smooth muscle cells (A10 cells). ALA significantly induced HO-1 expression accompanied by an increase in HO activity in A10 cells. Pretreatment with ALA increased the resistance of A10 cells to hydrogen-peroxide-induced oxidant stress. This protection of ALA was abrogated in the presence of the HO inhibitor zinc protoporphyrin IX. ALA significantly increased ROS, and this effect was blocked by N-acetyl-cysteine, which also inhibited ALA-induced activation of p44/42 mitogen-activated protein kinase (MAPK) and AP-1, HO-1 expression, and HO activity. These results suggest that ALA induces HO-1 expression through the production of ROS and subsequent activation of the p44/42 MAPK pathway and AP-1 in vascular smooth muscle cells. This study demonstrated that ALA increases the expression of HO-1, a critical cytoprotective molecule, and identified a novel pleiotropic effect of ALA on cardiovascular protection.