Lipoamide Research Articles

Lipoamide Alleviates Oxidized Fish Oil-Induced Host Inflammatory Response and Oxidative Damage in the Oviduct of Laying Hens.

Fish oil (FO) is an important source of lipid in functional food and aquafeeds. However, the harmful effects of oxidized fish oil (OFO) on host metabolism and reproductive health are not yet clear. In addition, lipoamide (LAM) has been widely studied as an agent for alleviating various diseases associated with oxidative disruption. Therefore, in the current study, to investigate the effects of LAM in alleviating OFO-induced decline in reproductive performance and oxidative damage to the oviduct in laying hens. We constructed a 1% fresh FO model, a 1% OFO model, and a LAM model with 1% OFO (OFO + LAM) added at 100 mg/kg to explore the antioxidant effect of LAM. Herein, these results were evaluated by breeding performance, immune responses, estrogen, and antioxidant indices of serum samples, as well as the number of follicles and antioxidant parameters of oviducts. From the results, compared with the FO group, OFO significantly decreased the egg-laying rate, increased the contents of total protein (TP) and inflammatory factors [tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-8, and interferon γ (INF-γ)], and reduced the concentrations of anti-oxidation [total antioxidant (T-AOC), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), glutathione (GSH), glutathione reductase (GR), catalase (CAT), and hydroxyl radical scavenging activity (HRSA)] in serum samples, as well as reduced the levels of anti-oxidation indexes in oviduct tissues (p < 0.05). Of note, the supplementation of LAM could significantly increase the laying performance, improve the levels of serum immunoglobulins (IgA, IgG, and IgM), serum estrogen [progesterone (P) and estradiol (E2)], and serum antioxidant parameters (T-AOC, T-SOD, GSH-Px, GSH, GR, CAT, and HRSA) and decrease the concentrations of serum inflammatory cytokines (TNF-α, IL-6, IL-8, and INF-γ) in laying hens following OFO administration (p < 0.05). In addition, LAM could dramatically increase the contents of antioxidant factors (p < 0.05) in oviducts and enhance the secretion capacity of the uterine part. Taken together, OFO caused host metabolic dysfunction, oxidative damage, uterine morphological abnormalities, and alterations of ovarian function. These results suggested that LAM administration could alleviate host metabolic dysfunctions and inflammatory damage, and then ameliorate oxidative damage in the oviduct induced by OFO, ultimately improving reproductive function.

Study of thermal properties of antioxidant lipoamide and its composites with colloid silica

Lipoamide (LM), amide of α-lipoic acid, is a very powerful antioxidant. However, information on its physicochemical properties, in particular on its thermal behavior, is very limited. In the present work, a DSC study of LM showed that heating above the melting point led to formation of a mixture of polymeric and crystalline forms of LM. In order to increase thermal stability of the drug, LM was encapsulated in colloid silica with various surface chemistry. It was found that encapsulation of LM in unmodified and organomodified silica materials slowed down the process of thermal degradation of the drug. The effect of silica matrix modification on the thermal degradation was revealed. It was shown that the interactions in the drug-silica composites play an important role in thermal stabilization of LM. The indicated thermal behavior of LM and α-lipoic acid in free form and in the synthesized composites was compared.

Lipoamide Ameliorates Oxidative Stress via Induction of Nrf2/ARE Signaling Pathway in PC12 Cells.

The mechanisms underlying neurodegenerative diseases are not fully understood yet. However, an increasing amount of evidence has suggested that these disorders are related to oxidative stress. We reported herein that lipoamide (LM), a neutral amide derivative of lipoic acid (LA), could resist oxidative stress-mediated neuronal cell damage. LM is more potent than LA in alleviating hydrogen peroxide- or 6-hydroxydopamine-induced PC12 cell injury. Our results reveal that LM promotes the nuclear accumulation of NFE2-related factor 2 (Nrf2), following with the activation of expression of Nrf2-governed antioxidant and detoxifying enzymes. Notably, silencing Nrf2 gene annuls the protection of LM, which demonstrates that Nrf2 is engaged in this cytoprotection. Our findings suggest that LM might be used as a potential therapeutic candidate for oxidative stress-related neurological disorders.

Lipoamide Acts as an Indirect Antioxidant by Simultaneously Stimulating Mitochondrial Biogenesis and Phase II Antioxidant Enzyme Systems in ARPE-19 Cells.

In our previous study, we found that pretreatment with lipoamide (LM) more effectively than alpha-lipoic acid (LA) protected retinal pigment epithelial (RPE) cells from the acrolein-induced damage. However, the reasons and mechanisms for the greater effect of LM than LA are unclear. We hypothesize that LM, rather than the more direct antioxidant LA, may act more as an indirect antioxidant. In the present study, we treated ARPE-19 cells with LA and LM and compared their effects on activation of mitochondrial biogenesis and induction of phase II enzyme systems. It is found that LM is more effective than LA on increasing mitochondrial biogenesis and inducing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its translocation to the nucleus, leading to an increase in expression or activity of phase II antioxidant enzymes (NQO-1, GST, GCL, catalase and Cu/Zn SOD). Further study demonstrated that mitochondrial biogenesis and phase II enzyme induction are closely coupled via energy requirements. These results suggest that LM, compared with the direct antioxidant LA, plays its protective effect on oxidative damage more as an indirect antioxidant to simultaneously stimulate mitochondrial biogenesis and induction of phase II antioxidant enzymes.

Novel lipopeptides, kiostostatins A-E from a marine-derived bacterium Bacillus subtilis

The producing strain 109GGC020 was isolated using a modified Bennett's agar plate from the marine sediment sample collected from Gageocho, Republic of Korea by serial dilution technique. This strain was identified as B. subtilis based on 16S rRNA sequencing. Microorganisms from marine origin continue to be a potential producers of bioactive secondary metabolites.1 Infact, they are ubiquitous in the marine environment and can tolerate adverse conditions such as high temperature, pressure, salinity and pH, and possess unique metabolic pathways that are different from their terrestrial counterparts.2 As a consequence, a large number of natural product research on marine-derived Bacillus sp. resulted in the discovery of a diverse class of secondary metabolites including lipopeptides, polypeptides, macrolactones, fatty acids, polyketides, lipoamides, and isocoumarins.3 As part of our ongoing research presenting new antimicrobials to meet increasing demands against rising multidrug resistant pathogens, we discovered five new linear lipopeptides, kiostostatins 1-5 from a marine-derived bacterium B. subtilis.

Gene mutations and prenatal diagnosis in families with maple syrup urine disease

Objective Maple syrup urine disease (MSUD) is a rare metabolic disorder caused by deficiency of the activity of branched-chain 2-keto acid dehydrogenase complex.The complex contains E1α,E1β and E2 subunits which are encoded by BCKDHA,BCKDHB or DBT genes respectively.Mutation in any gene will cause MSUD.The aim of this study was to analyze the gene mutations of four cases with MSUD and carry out prenatal diagnosis for these four families for MSUD.Methods From 2005 to 2010,four neonates (two males and two females) were diagnosed as MSUD at 2,5,10and 26 days of life.The coding regions of BCKDHA gene and BCKDHB gene in the above four cases were amplified by polymerase chain reaction and analyzed by direct DNA sequencing.During the second pregnancy of the same mother,the amniotic fluid was drawn out at 16-20 weeks for gene mutation analysis after the amniocytes were cultured.Results Mutation analysis revealed six mutations in four patients,including four novel mutations (c.308T＞C,c.562G＞T,c.1279C＞G and c.1280-1291de112) and two previously reported mutations.Five mutations (c.308T＞C,c.562G ＞T,c.868G＞A,c.1279C＞G and c.1280-1291de112) were detected on BCKDHA gene in three patients.While one mutation (c.853C＞T) was found on BCKDHB gene in one patient.Only one mutation was found in the amniocytes of each patient's mother at their second pregnancies suggesting a MSUD heterozygous fetus.Conclusions Analysis of BCKDHA and BCKDHB allowed preliminary understand of gene mutations in the four MSUD families,and made prenatal diagnosis possible,which helped in consultation in the second pregnancy. Key words: Maple syrup urine disease; 3-Methyl-2-oxobutanoate dehydrogenase (lipoamide); Pedigree; Prenatal diagnosis

Lipoic acid stimulates cAMP production via G protein-coupled receptor-dependent and -independent mechanisms

Lipoic acid (LA) is a naturally occurring fatty acid that exhibits anti-oxidant and anti-inflammatory properties and is being pursued as a therapeutic for many diseases including multiple sclerosis, diabetic polyneuropathy and Alzheimer's disease. We previously reported on the novel finding that racemic LA (50:50 mixture of R-LA and S-LA) stimulates cAMP production, activates prostanoid EP2 and EP4 receptors and adenylyl cyclases (AC), and suppresses activation and cytotoxicity in NK cells. In this study, we present evidence that furthers our understanding of the mechanisms of action of LA. Using various LA derivatives, such as dihydrolipoic acid (DHLA), S, S-dimethyl lipoic acid (DMLA) and lipoamide (LPM), we discovered that only LA is capable of stimulating cAMP production in NK cells. Furthermore, there is no difference in cAMP production after stimulation with either R-LA, S-LA or racemic LA. Competition and synergistic studies indicate that LA may also activate AC independent of the EP2 and EP4 receptors. Pretreatment of PBMCs with KH7 (a specific peptide inhibitor of soluble AC) and the calcium inhibitor (Bapta) prior to LA treatment resulted in reduced cAMP levels, suggesting that soluble AC and calcium signaling mediate LA stimulation of cAMP production. In addition, pharmacological inhibitor studies demonstrate that LA also activates other G protein-coupled receptors, including histamine and adenosine but not the β-adrenergic receptors. These novel findings provide information to better understand the mechanisms of action of LA, which can help facilitate the use of LA as a therapeutic for various diseases.

Lipoamide protects retinal pigment epithelial cells from oxidative stress and mitochondrial dysfunction

α-Lipoic acid (LA) has been widely studied as an agent for preventing and treating various diseases associated with oxidative disruption of mitochondrial functions. To investigate a related mitochondrial antioxidant, we compared the effects of lipoamide (LM), the neutral amide of LA, with LA for measures of oxidative damage and mitochondrial dysfunction in a human retinal pigment epithelial (RPE) cell line. Acrolein, a major component of cigarette smoke and a product of lipid peroxidation, was used to induce oxidative mitochondrial damage in RPE cells. Overall, using comparable concentrations, LM was more effective than LA at preventing acrolein-induced mitochondrial dysfunction and oxidative stress. Relative to LA, LM improved ATP levels, membrane potentials, and activities of mitochondrial complexes I, II, and V and dehydrogenases that had been decreased by acrolein exposure. LM reduced acrolein-induced oxidant generation, calcium levels, protein oxidation, and DNA damage to a greater degree than LA. And, total antioxidant capacity, glutathione content, glutathione S-transferase, and superoxide dismutase activities and expression of nuclear factor-E2-related factor 2 were increased by LM relative to LA. These results suggest that LM is a more potent mitochondrial-protective agent and antioxidant than LA in protecting RPE from oxidative damage.

-Lipoic acid and -lipoamide prevent oxidant-induced lysosomal rupture and apoptosis

-Lipoic acid (LA) and its corresponding derivative, -lipoamide (LM), have been described as antioxidants, but the mechanisms of their putative antioxidant effects remain largely uncharacterised. The vicinal thiols present in the reduced forms of these compounds suggest that they might possess metal chelating properties. We have shown previously that cell death caused by oxidants may be initiated by lysosomal rupture and that this latter event may involve intralysosomal iron which catalyzes Fenton-type chemistry and resultant peroxidative damage to lysosomal membranes. Here, using cultured J774 cells as a model, we show that both LA and LM stabilize lysosomes against oxidative stress, probably by chelating intralysosomal iron and, consequently, preventing intralysosomal Fenton reactions. In preventing oxidant-mediated apoptosis, LM is significantly more effective than LA, as would be expected from their differing capacities to enter cells and concentrate within the acidic lysosomal compartment. As previously reported, the powerful iron-chelator, desferrioxamine (Des) (which also locates within the lysosomal compartment), also provides protection against oxidant-mediated cell death. Interestingly, although Des enhances the partial protection afforded by LA, it confers no additional protection when added with LM. Therefore, the antioxidant actions of LA and LM may arise from intralysosomal iron chelation, with LM being more effective in this regard.

Preformulation study of the vaccine candidate P64k against Neisseria meningitidis.

We have previously isolated, cloned and expressed in Escherichia coli the lpdA gene coding for a high-molecular-mass protein (P64k) common to many meningococcal strains. P64k is an outer membrane lipoamide dehydrogenase that is highly immunogenic in animals. Here we describe a preformulation study of the recombinant protein as a vaccine candidate against Neisseria meningitidis, in which six variants containing the candidate were tested. Three assays were used to identify the most suitable variant for further evaluation: percentage of adsorption, identification of P64k by SDS/PAGE, and immunogenicity in mice. All the preformulation variants studied showed more than 98% of adsorption of P64k on the aluminium gel. After desorption, P64k was also identified by SDS/PAGE in the six preformulation variants. Seroconversion was attained in all groups analysed. On the basis of these results, the most effective variant consisted of 20 microg/ml P64k plus 0.5 mg/ml aluminium hydroxide.

Reaction of alcohol radicals with cyclic disulfides. An optical and conductimetric pulse radiolysis study

The disulfides lipoamide (LIPA) and oxidized dithiothreitol ( ox-DTT) react with methanol, ethanol, isopropanol and t-butanol radicals in aqueous solution at pH10.8 to form disulfide radical anions. Electron transfer rates range from ca 10 7 dm 3 mol -1s -1 for t-butanol radicals with LIPA to 3.6 × 10 8 dm 3 mol -1s -1 for methanol radicals with LIPA. The formations of the disulfide radical anions were followed by simultaneously monitoring absorption changes at 400 nm and changes in conductance with time. The electron transfer efficiencies are higher for LIPA than for ox-DTT increasing in the series t-butanol ⪡isopropanol 〈ethanol ∼methanol and are less than the proportion of α-carbon radical formation on the alcohols.

Polymer‐immobilized lipoamides—iron(II) system as a reducing catalyst for the reduction of nitrobenzenes to anilines by sodium borohydride

AbstractBased on a redox function of 1,2‐dithiolane ⇌ 1,3‐dithiol, lipoamide (LAm), and polymers having lipoamide structure were found to work as reducing catalysts for the reduction of p‐substituted nitrobenzenes to corresponding anilines with sodium borohydride in the presence of ferrous chloride in ethanol. Polyallylamine having lipoamide structure (PAA—LAm) showed a good reactivity for the reduction and was easily separated from the reaction mixture.

Preparation of a polymeric membrane with lipoamide structure and its application to electron transport across membrane

AbstractA lipoamide (LAm) structure was introduced into a polymeric membrane by chemical modification of poly(γ‐methyl‐D‐glutamate) (PMG). A. redox reaction proceeded across the membrane mediated by pendant LAm groups as solid carriers. It is suggested that the electron transport process in the membrane is derived from the exchange reaction between reduced LAm (thiol) and LAm (disulfide).

The pyruvate-oxidation system of the lipoamide dehydrogenase-containing anaerobe Peptococcus glycinophilus

The pyruvate-oxidation system of the lipoamide dehydrogenase-containing anaerobe <i>Peptococcus glycinophilus</i>