Effect of SP-A/B in lipoic acid on acute paraquat poisoning

BACKGROUND: This study was undertaken to observe the concentration of SP-A/B and the pulmonary surfactant in the lung tissue of rats with acute lung injury/acute respiratory distress syndrome caused by paraquat poisoning after the treatment of metabolic antioxidant-lipoic acid and whether its influence was related to TNF-α.METHODS: Sixty-six male Sprage-Dawley rats were randomly divided into three groups: normal control group(NS group), 6 rats; paraquat poisoning group(PQ group), 30 rats; and paraquat+lipoic acid treatment group(LA group), 30 rats. The rats in the PQ and LA groups were subdivided into 3-, 6-, 12-, 24-, 48-hour subgroups, with 6 rats in each group. After the rats were sacrificed, lung tissue from the same part was taken from the rats. After HE staining, histological changes were observed in the tissue under a light microscope. Lung tissue was also taken to test the levels of superoxide dismutase(SOD) and malondialdehyde(MDA). Whole blood(0.8 mL) without anticoagulant was drawn from the tail vein of rats for the determination of the TNF-α level. The total RNA of the lung tissue was collected, and the Rt-PCR method was used to measure the levels of SP-A and SP-B mRNA.RESULTS: HE staining showed that histopathological changes were milder in the LA group than in the PQ group. There were significant differences in MDA and SOD levels between different intervals both in intergroups and intragroups except the 3-hour subgroup(P<0.01). Likewise, the significant differences in the levels of TNF-α were also present between the three groups and between different intervals(P<0.01). The significant differences in SP-A mRNA and SP-B mRNA amplification ratio were seen between the three groups at the same intervals(P<0.01), but the differences between different intervals in the PQ group were statistically significant(P<0.05). The differences between different intervals in the LA group were statistically significant(P<0.01).CONCLUSION: Lipoic acid in acute paraquat poisoning could diminish lung tissue damage by regulating directly tumor necrosis factor and indirectly the content of pulmonary surfactant so as to reduce pulmonary edema, improve lung compliance, and finally protect lung tissues.

Partial Protection by Lipoic Acid Against Carboplantin-induced Ototoxicity in Rats

Objective To investigate the alterations in auditory brainstem evoked responses (ABRs) and the changes of carboplatin-induced ototoxicity in the cochlear oxidant/antioxidant systems and otoprotection by an antioxidant lipoate. Methods Male wistar rats were divided into four groups and treated as follows: 1) vehicle (saline) control, 2) carboplatin (256 mg/kg, i.p.), 3) lipoate (100 mg/kg, i.p.), 4) lipoate + carboplatin. Post-treatment ABRs were performed after four days and rats were sacrificed with their cochleae harvested and analyzed. Results Carboplatin significantly elevated ABR threshold above the pretreatment thresholds. Lipoate+carboplatin treated rats showed decreased elevation of hearing threshold. Carboplatin significantly depleted cochlear reduced to oxizized glutathione (GSH/GSSG) ratio, whereas lipoate+carboplatin treatment increased GSH/GSSG ratio. Carboplatin significantly decreased cochlear copper zinc-superoxide dismutase (CuZn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and glutathione-S-transferase (GST) activities and enzyme protein expressions and a significant increase in Mn-SOD activity, protein expression and malondialdehyde (MDA) level. Cochlear antioxidant enzyme activities, enzyme protein expressions and MDA level were partially restored in lipoate+carboplatin treated rats, compared to carboplatin alone. Conclusion Carboplatin-induced ototoxicity is related to impairment of cochlear antioxidant system and otoprotection conferred by lipoate is associated with partial sparing of the cochlear antioxidant defense system.

Protective Roles of α-lipoic Acid in Rat Model of Mitochondrial DNA4834bp Deletion in Inner Ear

The protective roles of α-lipoic acid in the rat model of mitochondrial DNA (mtDNA) 4834bp deletion in inner ear were investigated. Forty female Wistar rats at 4 weeks of age were divided into four groups: group A (D-galactose group, n=10), group B (D-galactose+α-lipoic acid group, n=10), group C (α-lipoic acid group, n=10), and group D (control group, n=10). Auditory brainstem response (ABR) was used to detect the hearing threshold. Colorimetry was used to analyze activity of superoxide dismutase (SOD) and concentration of malondialdehyde (MDA). The percentage of mtDNA4834bp deletion in inner ear was identified by real-time PCR. There was no significant difference in ABR threshold shift among all groups. The percentage of mtDNA4834bp deletion in group A was higher than that in other groups, but there was no significant difference in percentage of mtDNA4834bp deletion among groups B, C, and D. The activity of SOD in group A was lower than that in other groups. The concentration of MDA in group A was higher than that in other groups. It was concluded that there was no significant hearing loss when the percentage of mtDNA4834bp deletion was lower than 12.5%. α-Lipoic acid could prevent the reactive oxygen species (ROS)-induced mtDNA4834bp deletion in inner ear of rats.

Mechanism of alpha-lipoic acid in attenuating kanamycin-induced ototoxicity

In view of the theory that alpha-lipoic acid effectively prevents cochlear cells from injury caused by various factors such as cisplatin and noise, this study examined whether alpha-lipoic acid can prevent kanamycin-induced ototoxicity. To this end, healthy BALB/c mice were injected subcutaneously with alpha-lipoic acid and kanamycin for 14 days. Auditory brainstem response test showed that increased auditory brainstem response threshold shifts caused by kanamycin were significantly inhibited. Immunohistochemical staining and western blot analysis showed that the expression of phosphorylated p38 mitogen-activated protein kinase and phosphorylated c-Jun N-terminal kinase in mouse cochlea was significantly decreased. The experimental findings suggest that phosphorylated p38 and phosphorylated c-Jun N-terminal kinase mediated kanamycin-induced ototoxic injury in BALB/c mice. AIpha-lipoic acid effectively attenuated kanamycin ototoxicity by inhibiting the kanamycin-induced high expression of phosphorylated p38 and phosphorylated c-Jun N-terminal kinase.

Self-Assembled Monolayer of Lipoic Acid on Gold and Its Application to Rapid Determination of 2, 3, 7, 8-Tetrachlorodibenzo-p-Dioxin

Lipoic acid (LA) has received great attention in the area of gold surface functionalization. In this study, LA was employed as a linker for the attachment of antibody to the gold surface of surface plasmon resonance (SPR) chip. By using this chip in a homemade SPR immunosensor, low molecular weight compound 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) can be detected at a low level of 0.01 ng/mL. There is a good linear relationship(R2 =0.943 1) between the results of SPR biosensor and enzyme-linked immunosorbent assay(ELISA).

Dose-effect Study of Lipoic Acid Supplementation on Growth Performance in a Weaned Rat Model

The present study investigated the doseeffect relationship of graded levels of lipoic acid supplementation on growth performance and small intestinal development in a weaned rat model. Seventy-two weaned Sprague-Dawley rats, were fed semipurified diets （ n = 12 ）, either unsupplemented （ group I） or supplemented with 12.5,25,125, or 250 mg/kg body weight （ BW ） lipoic acid （ groups HI, IV, V, and VI）, with 200 mg/kg BW aureomycin as the antibiot- ic control （ group II）. The experiment lasted 21 days. Growth performance was not significantly different （P 〉 0.05） between rats under the antibiotic control （group I） and rats fed low levels （12. 5 and 25 mg/kg BW） of lipoic acid （groups III and IV）. In contrast,high level （125 and 250 mg/kg BW） lipoic acid supplementation （groups V and VI） （P 〈 0.05 ） reduced weight gain, feed consumption, and feed efficiency. In addition, high levels （125 and 250 mg/kg BW） of lipoic acid significantly （P 〈 0.05） reduced the villus height/crypt depth ratio, as well as the numbers of lactobacillus, total aerobes, and total anerobes in the gastrointestinal tract compared with the other treatments, which meant that high levels of lipoic acid impaired intestinal morphology and disordered the balance of intestinal microbiology. Furthermore,the results showed that high levels of lipoic acid supplementation （ P 〈 0.05 ） elevated interferon- γ and interleukin-2, but dramatically （ P 〈 0.05 ） depressed interleukin-4 and interleukin-10 compared with the low levels of lipoic acid supplementation and the control group, which indicated that high levels of lipoic acid would induce bias of Th1/Th2 lymphocytes. Taken together, the results indicate that lipoic acid supplementation can＇ t improve growth performance and intestinal development of normal animals, especially,high levels （ ≥ 125 mg/kg BW） of lipoic acid supplementation restrained growth performance and intestinal development, in association with unbalance of certain cytokines.

Symptomatic and pathogenetic treatment of diabetic neuropathy Role of alpha-lipoic acid

Diabetic neuropathy, the most common form of peripheral neuropathy, presents as different forms of focal or diffuse neuropathy, including the disabling, or potentially life-threatening clinical entities of painful diabetic neuropathy, autonomic neuropathy, and diabetic foot. The pathogenesis of diabetic neuropathy results from the concurrent action of various intersecting factors of nerve damage, such as oxidative stress and mitochondrial dysfunction, inflammation, microangiopathy and ischemia, triggered by hyperglycemia and related biochemical changes. Symptomatic treatment of diabetic neuropathy mainly concerns therapies for neuropathic pain, interventions targeted at the organ systems involved in autonomic neuropathy, and management of diabetic foot. Therapeutic approaches to the pathogenesis of diabetic neuropathy have focused on the different components of the causes of nerve damage, particularly oxidative stress, which has been demonstrated to play a central role. Alpha-lipoic acid, a potent lipophilic free radical scavenger, has been used in treatment of patients with diabetic neuropathy, displaying efficacy on the chief symptoms, including neuropathic pain, and showing that neuropathic deficits may be improved by treatment. Current evidence suggests a possible efficacy of alpha-lipoic acid not only for neuropathic symptoms, but also for reducing the risk factors for diabetic neuropathy.

Clinical effect of external counterpulsation combined with lipoic acid on patients with type 2 diabetic foot of grade 0-2

Objective:To analyze the clinical efficacy and safety of external counterpulsation combined with lipoic acid in the treatment of patients with type 2 diabetic foot of grade 0-2.Methods:62 patients with diabetic foot from January 2019 to October 2020 were selected and divided into control group and external counterpulsation group according to different treatment schemes,31 cases in each group.The control group was given intravenous lipoic acid,and the external counterpulsation group was given external counterpulsation combined with intravenous lipoic acid.The clinical efficacy and adverse reactions of the two groups were compared,and the blood flow parameters,ankle brachial index and common peroneal nerve conduction velocity of the two groups before and after treatment were compared.Results:The total effective rate of the treatment group(93.54%)was significantly higher than that of the control group(48.38%)(P<0.05).After treatment,the vessel diameter of dorsalis pedis artery(2.552±0.024mm)and ankle brachial index(0.923±0.036)in ECP group were significantly higher than those in control group(1.864±0.020)and ankle brachial index(0.843±0.030)(P<0.05).After the control group and the external counterpulsation group were treated,the levels of serum of VEGF,bFGF、IGF-1(85.479±4.239,148.27±14.25,62.33±3.75;94.163±8.917,200.88±14.58,81.35±1.08)was significantly higher than that before treatment(57.264±0.801,106.44±3.83,30.90±0.42;57.133±0.850,106.78±3.69,31.01±0.56),the levels of MMP-2(2.035±0.08,1.417±0.21)after treatment in the control group and the external counter stroke group after treatment(2.035±0.08,1.417±0.21)was significantly lower than that after treatment.The levels of VEGF,bFGF and IGF-1 in ECP group were significantly higher than those in control group,and MMP-2 was significantly lower than that in control group(P<0.05).Conclusion:The clinical effect of external counterpulsation combined with lipoic acid in the treatment of type 2 diabetic foot with grade 0-2 is significant,which can effectively improve the blood flow parameters of dorsal foot artery,ankle brachial index and common peroneal nerve conduction velocity,with less adverse reactions.

Storage Stability of Alpha-Lipoic Acid-loaded Lipid Nanoparticles

Alpha-lipoic acid-loaded lipid nanoparticles(ALA-LNs) were prepared by high pressure homogenization method.The influences of storage conditions such as time and temperature on the physical and chemical storage stability of ALA-LNs were studied in details.The stability was evaluated by particle size and polydispersity index,morphology of ALA-LNs,and capacity of ALA loading.The dilution and pH stability of ALA-LNs suspensions were also studied.After three months storage,the mean size of ALA-LNs at 4 and 40 ℃ was increased by 2.68% and 3.62% compared with the original size,respectively.ALA-LNs stored at 40 ℃ had ellipsoid shape and the mean size was about 152 nm(SD=23.6).The loading capacity of ALA at 40 ℃ was much higher than those stored at other two temperatures.The good dilution and pH stability were also demonstrated.The sample had good fluidity even at 4 ℃.

Determination of Alpha-Lipoic Acid in a Nutritional Supplement Using High Performance Liquid Chromatography

Alpha lipoic acid has the ability to react and neutralize reactive oxygen species (ROS) such as superoxide radicals, simple oxygen, hydroxyl radicals, hypochlorous acid and peroxyl radicals. A rapid high-performance liquid chromatographic method for determination of lipoic acid in a nutritional supplement was developed. The method involved sample preparation and the mobile phase comprised of 50 mM disodium hydrogen phosphate buffer (pH 2.5 adjusted with 1 M H3PO4): acetonitrile in the ratio of 50:50. The separation was done using a C18 column (150 mm) and detection was carried out using UV detection at 201 nm. The assay was found to be linear in the range of 1.56 - 50 μg/mL with the correlation coefficient of 0.9997. Method precision was determined while LOD was 0.05 μg/mL and LOQ 0.15 μg/mL. The chromatographic peak LA retention time was 6 min.

Alpha lipoic acid protects lens from H_2O_2-induced cataract by inhibiting apoptosis of lens epithelial cells and inducing activation of anti-oxidative enzymes

Objective:To determine whether alpha lipoic acid（LA）can effectively protect lenses from hydrogen peroxide（H2O2）-induced cataract.Methods:Lens from adult Sprague-Dawley rats were cultured in 24-well plates and treated without or with 0.2 mM of H2O2,0.2 mM of H2O2 plus 0.5 mM.1.0 mM.or 2.0 mM of LA for 24 h.Cataract was assessed using cross line grey scale measurement.Superoxide dismutase（SOD）.glutathione（GSH-Px）.lactate dehydrogenase（LDH）. and maloudialdehyde（MDA）activity or level in lens homogenates was measured.Apoptosis of lens epithelial cells in each group were detected by Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling（TUNEL） Assay.Results:A total of 0.2 mM of H2O2 induced obvious cataract formation and apoptosis in lens’ epithelial cells,but 0.5-2.0 mM of LA could block the effect of 0.2 mM H2O2 in inducing cataract and apoptosis.Furthermore.0.2 mM ol H2O2 significantly decreased SOD.GSH-Px,and LDH activity and significant increased MDA level in the lens,but 0.5-2.0 mM of LA blocked the effect of 0.2 mM H2O2.One mM of LA was found to be the most effective. Conclusions:LA can protect lens from H2O2-induced cataract.LA exerts protective effects through inhibition of lens’ epithelial cell apoptosis and activation of anti-oxidative enzymes.

Lipoic acid suppresses portal endotoxemia-induced steatohepatitis and pancreatic inflammation in rats

AIM: To examine the effect of α-lipoic acid (LA) on mild portal endotoxemia-induced steatohepatitis and associated pancreatic abnormalities in fructose-fed rats. METHODS: Rats were randomly assigned into two groups with a regular or 60% fructose-enriched diet for 8 wk. After fructose feeding for 4 wk, rats were further divided into four subgroups: with intraportal saline (F PV ), with intraportal saline plus administration of LA (F PV + LA ), with lipopolysaccharide (LPS) infusion (F PLPS ), and with LPS infusion plus administration of LA (F PLPS + LA ). Rats were treated with LPS using intraportal infusion while LA was administered orally. Metabolite levels, superoxide levels, inflammatory markers, malondialdehyde content, glutathione content and toll-like receptor 4 (TLR4 ) gene expression were all measured using standard biochemical techniques. Pancreatic insulin secretion was evaluated by a hyperglycemic clamp technique. Histology of liver and pancreas tissues were evaluated using hematoxylin and eosin staining and immunohistochemistry. RESULTS: Fructose-induced elevation in plasma C-reactive protein, amylase, superoxide, white blood cell count as well as in hepatic and pancreatic contents of malondialdehyde, tumor necrosis factor alpha and interleukin-6 were increased in animals treated with LPS and reversed with LA administration. The augmented hepatic gene expression of TLR4 in fructose-fed rats was further increased in those with intraportal LPS infusion, which was partially reversed by LA administration. Pathological examination showed inflammatory changes and leukocyte infiltration in hepatic and pancreatic islets of animals treated with LPS but were rarely observed in those with LA treatment. In addition to affects on the liver, impaired pancreatic insulin secretion seen in fructose-fed rats was deteriorated in with LPS treatment and partially reversed with LA administration. CONCLUSION: These data suggest LA could significantly suppress mild portal-endotoxemia but not fructoseinduced liver and pancreatic abnormalities in a rodent model for metabolic syndrome.

Protective effects of lipoic acid-niacin dimers against blue light-induced oxidative damage to retinal pigment epithelium cells

AIM: To evaluate the protective effects of lipoic acid-niacin(N2 L) dimers against blue light(BL)-induced oxidative damage to human retinal pigment epithelium(hRPE) cells in vitro.METHODS: h RPE cells were divided into a control group(CG), a BL group, an N2 L plus BL irradiation group, an α-lipoic acid(ALA) plus BL group, an ALA-only group, and an N2 L-only group. hRPE cellular viability was detected by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium(MTT) bromide assays, and apoptosis was evaluated by annexin-V-PE/7-AAD staining followed by flow cytometry. Ultrastructural changes in subcellular organelles were observed by transmission electron microscopy. Reactive oxygen species formation was assayed by flow cytometry. The expression levels of the apoptosis-related proteins BCL-2 associated X protein(BAX), B-cell leukmia/lymphoma 2(BCL-2), and caspase-3 were quantified by Western blot analysis.RESULTS: BL exposure with a light density of 4±0.5 mW/cm2 exceeding 6 h caused hRPE toxicity, whereas treatment with a high dose of N2 L(100 mol/L) or ALA(150 mol/L) maintained cell viability at control levels. BL exposure caused vacuole-like degeneration, mitochondrial swelling, and reduced microvillus formation;however, a high dose of N2 L or ALA maintained the ultrastructure of hRPE cells and their organelles. High doses of N2 L and ALA also protected hRPE cells from BL-induced apoptosis, which was confirmed by Western blot analysis: BCL-2 expression significantly increased, while BAX and caspase-3 expression slightly decreased compared to the CG.CONCLUSION: High-dose N2 L treatment(>100 mol/L) can reduce oxidative damage in degenerating hRPE cells exposed to BL with an efficacy similar to ALA.

Effects of dietary CoQ₁₀and α-lipoic acid on CoQ₁₀levels in plasma and tissues of eggs laying hens

In this paper we described the effect of administrated CoQ10, and alfa-lipoic acid on the concentration of total CoQ10 inplasma end body tissues of eggs laying hens. Organisms raise a complex network of enzymes, metabolites and molecules with antioxidant activities in order to prevent oxidative damage of theirs bodies. Adequate blood concentrations of small weight molecules ingested with food and food additives are important for the proper functioning of the antioxidant defense. To test this hypothesis we prepared following experiment. Forty weeks old hens were selected from two genotypes;Ross 308 broiler mothers and Lohmann breed hens. Animals were fed for a period of 84 days. Concentrations of supplemented CoQ10 and ALAwere calculated from feed instruction tables so each hen received an average of approximately 5 mg of CoQ10 and 50 mg ofALAper kg of animal weight per day. During the experiment blood samples were taken and at the end of the experiment different body tissues (heart, liver, breast, legs) were collected and analyzed with originally developed HPLC-MS/MS method based selective ionization with LiCl on MRM scanning. We found a number of interesting and unexpected results. Supplemented CoQ10 increased concentrations of coenzyme CoQ10 inplasma and different hen’s tissues. Increased concentration of CoQ10 is the result of its transfer with chylomicrons from the digestive tract to various organs of the body and to the liver where exogenous and endogenous CoQ10 has been re-redistributed through lipoproteins. Supplemented ALA caused much greater concentration of CoQ10 indifferent tissues and plasma then CoQ10. Plausible explanation of our results is such that ALA may regenerates the antioxidants and accelerate the formation of endogenous CoQ10 which is distributed with lipoprotein carriers and increases overall concentration of CoQ10. Our experiments definitely show that Lipoic acid beside glutathione promotes also a synthesis of CoQ10 and increases the total concentration especially in liver and heart tissues.

Post-Marketing Surveillance of Fixed Dose Combination of Methylcobalamin, Alpha Lipoic Acid, Folic Acid, Biotin, Benfotiamine &Vitamin B6-Nutripathy for the Management of Peripheral Neuropathy

Background: Peripheral neuropathy is a commonly encountered troublesome condition which is often disabling & worsens when left untreated. Traditional neuropathic pain medications primarily provide symptomatic relief;however, the pathogenesis of nerve damage remains unresolved. Extensive literature survey reveals that patients with peripheral neuropathy experience significant benefits with the use of B-vitamins like methylcobalamin (B12), folic acid (B9), biotin (B7), benfotiamine (B1) and pyridoxine (B6). The other well documented antineuropathic agents include alpha lipoic acid, glutathione, omega fatty acids, myoinositol, certain trace elements, etc. Materials and Methods: A multicentre, prospective, open-label, non-comparative clinical study was carried out in 497 patients with peripheral neuropathy. A fixed dose combination of methylcobalamin, alpha lipoic acid (ALA), folic acid, biotin, benfotiamine & vitamin B6 capsule was orally administered once daily for 12 weeks. Results: Treatment led to significant reduction from baseline score in various neuropathy symptoms from the 4th week itself. After 12 weeks of treatment, the mean pain score declined by 78.0%, numbness by 92.1% and muscle weakness by 96.9%. Also, there was 96.0% & 99.2% reduction in tingling & burning sensation respectively. No serious adverse events were reported.Conclusion: The current study confirms that fixed dose combination of methylcobalamin, ALA, folic acid, biotin, benfotiamine & vitamin B6 is effective & well tolerated in the management of peripheral neuropathy.

Effect of alpha-lipoic acid supplementation on blood pressure, renal oxidant-antioxidant status and renal damage in spontaneously hypertensive rats

Objective:To investigate the effect of alpha-lipoic acid(ALA)supplementation on systolic blood pressure(SBP),renal oxidant-antioxidant status and renal damage in spontaneously hypertensive rats(SHR)and SHR administered with Nω-nitro-L-arginine methyl ester(L-NAME).Methods:Male rats were divided into four groups(SHR,SHR+ALA,SHR+L-NAME,SHR+ALA+L-NAME).The respective group of rats was administered with ALA(100 mg/kg/day)from age 4 weeks to 28 weeks and L-NAME(25 mg/kg/day)from age 16 weeks to 28 weeks.SBP was measured every two weeks and twenty four hour urine was collected at 4 weeks,16 weeks and 28 weeks for estimation of protein,creatinine and N-acetyl-e end of 28 weeks,rats were sacrificed and blood and kidneys colα-Dglucosaminidase.At thlected for assessment of blood creatinine,kidney thiobarbituric acid reactive substances,protein carbonyls,superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase,glutathione S-transferase,glutathione disulfide,glutathione,total antioxidant status and nitric oxide as well as histopathological examination.Results:ALA supplementation significantly reduced SBP of SHR and SHR+L-NAME rats when compared to their respective non-supplemented groups.Renal oxidant status markers including thiobarbituric acid reactive substances and protein carbonyls were significantly reduced on SHR and SHR+L-NAME rats supplemented with ALA at 28 weeks as well as ALA supplementation significantly increased renal antioxidants including superoxide dismutase,catalase,glutathione peroxidase,glutathione S-transferase,glutathione and glutathione/glutathione disulfide ratio at 28 weeks.No significant change in nitric oxide levels was observed between the ALA supplemented and non-supplemented groups.Renal dysfunction was ameliorated on ALA supplementation as evidenced by significant reduction in urine protein levels,N-acetyl-α-D-glucosaminidase activity and significant increase of creatinine clearance in SHR and SHR+L-NAME at 28 weeks.Renal histopathological examination showed that ALA supplementation prevented vascular damage in SHR and ameliorated glomerular damage in SHR+L-NAME at 28 weeks.Conclusions:ALA has hypotensive and renoprotective effects on both SHR and SHR+LNAME,which could be due to its ability to ameliorate oxidative stress in the kidneys.

Effect of -Lipoic Acid on Proteasomal Induction: Protection against Oxidative Damage in Human Skin Fibroblasts Cell Line NHDF

As human skin is daily exposed to oxidative stress causing various unesthetical abnormalities, the road to effective anti-aging substances is being widely investigated. 20S proteasome is a key pathway in the breakdown of oxidized proteins. But its activity declines dramatically in aging cells. Nrf2 inducers -lipoic acid (LA) and sulforaphane (SFN) have been described in the dietary industries for their antioxidant effects on various cell lines. However, since little is yet known about LA’s capacity to protect skin cells from premature and extrinsic aging;our aim was to demonstrate the beneficial effect of LA on the cellular detoxification systems. On this purpose, we evaluated its effects against injuries induced by H2O2 in NHDF and its likely positive effect on the chymotrypsin-like (CT-like) activity of 20S proteasome, using SFN as a reference. The cellular content in proteins was measured, as well as the production of Reactive Oxygen Species (ROS). Also, the induction of the proteasomal protein expression was investigated. The results show that after 48 h treatment, LA significantly decreased the percentage of ROS positive cells. Also, LA decreased the level of H2O2-induced carbonylated proteins and increased the proteasomal activity. Furthermore, LA upregulated the expression of the 20S proteasome &#223;-subunit responsible for the CT-like activity (PSMB5). Overall, both molecules enhanced cell proliferation over 8 days. So, our investigation found evidence of the higher capacity of LA to induce 20S proteasome activity with less toxicity in human fibroblasts compared to reference molecule SFN. These results tend to demonstrate that the induction of the proteasomal activity might be a part of the antioxidant potential of LA. To our knowledge, this is the first study to elucidate the capacity of LA to activate detoxification systems in human cell lines through the induction of 20S proteasome.

Efficacy of Magnesium and Alpha Lipoic Acid Supplementation in Reducing Premature Uterine Contractions

Objective: Premature uterine contractions represent one of the major symptoms related to preterm labor. So far, primary prevention of preterm labor is based on the early identification of symptoms and on pharmacological treatments which are prone of several secondary effects. In this double-blinded, randomized, placebo-controlled trial, the efficacy of a supplementation of magnesium and alpha-lipoic acid has been evaluated. Methods: Three hundred pregnant women at 14 - 34 weeks of gestation were enrolled and randomly divided to receive a daily single tablet containing a supplement of magnesium and alpha-lipoic acid (DAV&reg;LoLiPharmasrl, Rome-Italy) or placebo until delivery. The incidence of episodes of preterm uterine contraction, associated or not with pain, as well as maternal need of hospitalization was evaluated. Results: Magnesium and lipoic acid supplementation was effective to significantly reduce the incidence of preterm uterine contractions compared to placebo. In particular, 52% of women who received the supplementation reported no symptoms of preterm uterine contractions throughout pregnancy, and persistent episodes of uterine contractions were significantly reduced compared to placebo (20% vs 60%, respectively). Furthermore, only 20% of subjects who received the supplementation required hospitalization, while it has been necessary for 40% of women who received placebo. Conclusions: Our findings suggest that supplementation with magnesium and lipoic acid is effective in reducing the incidence of premature uterine contraction and related episodes of hospitalization, compared to placebo. Nevertheless, further studies based on larger cohorts of patients are necessary to confirm the efficacy of these preliminary results.

Pharmacokinetics of lipoic acid in healthy Chinese volunteers after single and multiple doses of Lipoic acid dispersible tablets

This study aimed to evaluate the pharmacokinetics for lipoic acid （LA） after oral administration of 12 healthy Chinese volunteers with single and multiple-dose of lipoic acid dispersal tablets using a liquid chromatography-temdend mass spectrometry （LC-MS/MS） methods. In single-dose study, healthy Chinese male and female volunteers received three dose levels at 0.2, 0.3, and 0.4 g of LA dispersal tablets with a 3 x3 Latina square design. In multiple-dose study, 12 healthy Chinese volunteers received orally a 0.1 g of LA dispersible tablet three times daily for 6 consecutive days and 0.3 g once on day 7. The results showed that pharmacokinetics of LA fitted a two-compartment open model. The values of area under the curve （A UC） increased proportionally within the range of 0.2-0.4 g, while the Vd/F, CL/F, MRT, t1/2 and tmax of LA were similar at three dose levels. The steady-state pharmacokinetic parameters of LA were similar to those following a single dose and no accumulation was found following multiple-dose of LA dispersal tablets.

Attenuation of myocardial apoptosis by alpha-lipoic acid through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy

Background Cardiac failure is a leading cause of the mortality of diabetic patients. In part this is due to a specific cardiomyopathy, referred to as diabetic cardiomyopathy. Oxidative stress is widely considered to be one of the major factors underlying the pathogenesis of the disease. This study aimed to test whether the antioxidant α-lipoic acid （α-LA） could attenuate mitochondrion-dependent myocardial apoptosis through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy. Methods A rat model of diabetes was induced by a single tail intravenous injection of streptozotocin （STZ） 45 mg/kg. Experimental animals were randomly assigned to 3 groups： normal control （NC）, diabetes （DM） and DM treated with α-LA （α-LA）. The latter group was administered with a-LA （100 mg/kg ip per day）, the remainder received the same volume vehicle. At weeks 4, 8, and 12 after the onset of diabetes, cardiac apoptosis was examined by TUNEL assay. Cardiomyopathy was evaluated by assessment of cardiac structure and function. Oxidative damage was evaluated by the content of malondialdehyde （MDA）, reduced glutathione （GSH） and the activity of manganese superoxide diamutase （Mn-SOD） in the myocardial mitochondria. Expression of caspase-9 and caspase-3 proteins was determined by immunohistochemistry and mitochondrial cytochrome c release was detected by Western blotting Results At 4, 8, and 12 weeks after the onset of diabetes, significant reductions in TUNEL-positive cells, caspase-9,-3 expression, and mitochondrial cytochrome c release were observed in the α-LA group compared to the DM group. In the DM group, the content of MDA in the myocardial mitochondria was significantly increased, and there was a decrease in both the mitochondrial GSH content and the activities of Mn-SOD. They were significantly improved by α-LA treatment. HE staining displayed structural abnormalities in diabetic hearts, while α-LA reversed this structural derangement. The index of cardiac function （±dp/dtmax） in the diabetes group was aggravated progressively from 4 weeks to 12 weeks, but α-LA delayed deterioration of cardiac function （P 〈0.05）. Conclusions Our findings indicate that the antioxidant α-LA can effectively attenuate mitochondria-dependent cardiac apoptosis and exert a protective role against the development of diabetic cardiomyopathy. The ability of α-LA to suppress mitochondrial oxidative damage is concomitant with an enhancement of Mn-SOD activity and an increase in the GSH content of myocardial mitochondria.