Alpha-lipoic acid analogues in the regulation of redox balance in epilepsy: A molecular docking and simulation study

G6PD deficiency renders cells more susceptible to oxidative insults, while antioxidant dietary supplementation could restore redox balance and ameliorate exercise-induced oxidative stress. To examine the effects of alpha-lipoic acid (ALA) supplementation on redox status indices in G6PD deficient individuals, eight male adults with G6PD deficiency (D) participated in this randomized double-blind placebo-controlled crossover trial. Participants were randomly assigned to receive ALA (600 mg/day) or placebo for 4 weeks separated by a 4-week washout period. Before and at the end of each treatment period, participants exercised following an exhaustive treadmill exercise protocol. Blood samples were obtained before (at rest), immediately after and 1h after exercise for later analysis of total antioxidant capacity (TAC), uric acid, bilirubin, thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PC). ALA resulted in significantly increased resting TAC and bilirubin concentrations. Moreover, TAC increased immediately and 1h after exercise following both treatment periods, whereas bilirubin increased immediately after and 1h after exercise following only ALA. No significant change in uric acid, TBARS or PC was observed at any time point. ALA supplementation for 4 weeks may enhance antioxidant status in G6PD individuals; however, it does not affect redox responses to acute exercise until exhaustion or exercise performance.

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Physicochemical characterisation of dihydro-alpha-lipoic acid interaction with human serum albumin by multi-spectroscopic and molecular modelling approach

Journal of the Serbian Chemical Society ◽

10.2298/jsc210420041g ◽

2021 ◽

pp. 41-41

Author(s):

Nikola Gligorijevic ◽

Vladimir Sukalovic ◽

Simeon Minic ◽

Goran Miljus ◽

Olgica Nedic ◽

...

Keyword(s):

Molecular Docking ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Lipoic Acid ◽

Food Supplement ◽

Alpha Lipoic Acid ◽

Salt Bridges ◽

Preferential Binding ◽

Docking Approach

The binding of popular food supplement and a well-known anti-oxidant, dihydro-alpha-lipoic acid (DHLA) to human serum albumin (HSA) was characterised. The binding was monitored by several spectroscopic methods together with molecular docking approach. HSA was able to bind DHLA with moderate affinity, 1.00?0.05?104 M-1. Spectroscopic data demonstrated that the preferential binding site for DHLA on HSA is IIA (Sudlow I). Both experimental and molecular docking analysis identified electrostatic (salt bridges) and hydrogen bonds as the key interactions involved in DHLA binding to HSA. Molecular docking confirmed that Sudlow I site could accommodate DHLA and ligand is bound to the protein in a specific conformation. The molecular dynamic simulation showed that the formed complex is stable. Binding of DHLA does not affect the structure of protein, but it thermally stabilises HSA. Bound DHLA had no effect on the susceptibility of HSA to trypsin digestion. Since DHLA is a commonly used food supplement, the knowledge of its pharmacokinetics and pharmacodynamic properties in an organism is very important. This study further expands it by providing a detailed analysis of its interaction with HSA, the primary drug transporter in the circulation.

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The role and point of the disturbed redox balance in the development of diabetic neuropathy and antioxidant effects of alpha-lipoic acid

Endocrinology: News, Opinions, Training ◽

10.33029/2304-9529-2020-9-2-70-79 ◽

2020 ◽

Vol 9 (2) ◽

pp. 70-79

Author(s):

A.S. Ametov ◽

◽

A.A. Kosyan ◽

Keyword(s):

Diabetic Neuropathy ◽

Lipoic Acid ◽

Redox Balance ◽

Alpha Lipoic Acid ◽

Antioxidant Effects

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Dihydro-alpha-lipoic acid binds to human serum albumin at Sudlow I binding site

10.1101/2020.10.16.342121 ◽

2020 ◽

Author(s):

Nikola Gligorijević ◽

Vladimir Šukalović ◽

Goran Miljuš ◽

Olgica Nedić ◽

Ana Penezić

Keyword(s):

Molecular Docking ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Binding Site ◽

Lipoic Acid ◽

Electrostatic Interactions ◽

Dietary Intervention ◽

Alpha Lipoic Acid ◽

Preferential Binding

ABSTRACTBinding of dihydro-alpha-lipoic acid (DHLA) to human serum albumin (HSA) was characterised in detail in this study. Binding process was monitored by spectroscopic methods and molecular docking approach. HSA binds DHLA with moderate affinity, 0.80 ± 0.007 × 104 M−1. Spectroscopic data demonstrated that the preferential binding site for DHLA on HSA is IIA (Sudlow I). Hydrogen bonds and electrostatic interactions were identified as the key binding interactions. DHLA binding thermally stabilized HSA, yet it had no effect on HSA structure and its susceptibility to trypsin digestion. Molecular docking confirmed that Sudlow I site accommodated DHLA in a certain conformation in order for binding to occur. Molecular dynamic simulation showed that formed complex is stable. Reported results offer future perspectives for investigations regarding the use of DHLA as a dietary intervention but also raise concerns about the effectiveness of alpha-lipoic acid and DHLA in treatment of patients with COVID-19.

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