Most anti-tumor agents suffer from systemic non-specific distribution and low aggregation in tumors,which not only decreases the therapeutic efficacy,but also causes systemic toxic side effects in the treatments of tu...Most anti-tumor agents suffer from systemic non-specific distribution and low aggregation in tumors,which not only decreases the therapeutic efficacy,but also causes systemic toxic side effects in the treatments of tumors.In recent years,the rapid development of nanotechnology has brought new ideas for the application of anti-tumor drugs.Nanomedicines,such as liposomes and micelles,can improve drug targeting and prolong systemic circulation time to promote anti-tumor efficacy and reduce toxic side effects.However,conventional micelles bear the risk of instability and premature drug leaking in the blood circulation.We designed a reduction-responsive core-cross-linked micelle PTX@Fmoc-LA-PEG efficiently encapsulating Paclitaxel(PTX)viaπ-πstacking and hydrophobic interactions of Fmoc and PTX.Moreover,the micelle was further locked based on the cross-linking properties of the disulfide bonds formed by lipoic acid(LA).As expected,the core-cross-linked micelles PTX@Fmoc-LA-PEG remained stable in normal physiological environments,while restoring the normal drug release rate of micelles under the highly reducing environment due to LA unlocking.The blank micelles(Fmoc-LA-PEG)exhibited excellent biocompatibility,while the drug-loaded micelles(PTX@Fmoc-LA-PEG)displayed a remarkable anti-tumor effect in vitro and in vivo experiments.These results suggested that core-cross-linked micelles PTX@FmocLA-PEG have great potential to improve the targeting and stability of anti-tumor drugs.展开更多
The trial by Cano Contreras et al examined a proprietary formulation containing Silybum marianum and alpha-lipoic acid(SM-ALA),combined with a Mediter-ranean diet,in patients with metabolic dysfunction-associated stea...The trial by Cano Contreras et al examined a proprietary formulation containing Silybum marianum and alpha-lipoic acid(SM-ALA),combined with a Mediter-ranean diet,in patients with metabolic dysfunction-associated steatotic liver disease.While some metabolic benefits were observed,limitations such as the absence of an SM-ALA-only group,the lack of histological data,and a small sam-ple size reduce the validity of the findings.Future research should follow clinical trial standards for pharmacological studies,including phase 1/2 testing,validated outcomes,and transparency.展开更多
ObjectiveTo develop a sustained-release codelivery system for intratympanic administration of dexamethasone(DEX)and lipoic acid(LA).MethodsDEX microcrystals(MCs)were prepared via precipitation,while LA-loaded porous P...ObjectiveTo develop a sustained-release codelivery system for intratympanic administration of dexamethasone(DEX)and lipoic acid(LA).MethodsDEX microcrystals(MCs)were prepared via precipitation,while LA-loaded porous PLGA microspheres(LPMPs)were fabricated using a double emulsion–solvent evaporation method.DEX MCs were physically perfused into LPMPs via negative pressure to form a combined system(DEX MCs+LPMPs).Physicochemical properties,in vitro drug release,pharmacokinetics,and biocompatibility were evaluated.Guinea pigs were used for intratympanic injections of DEX MCs,LPMPs,or DEX MCs+LPMPs.ResultsThe DEX MCs+LPMPs system enabled simultaneous release of both drugs,with DEX exhibiting superior pharmacokinetics(sustained perilymph concentrations up to 7 days)compared to DEX MCs alone.LA release from LPMPs demonstrated prolonged kinetics without burst release.SEM confirmed DEX MCs were localized within/on LPMPs and adhered to the round window membrane(RWM).Histological analysis revealed normal cochlear morphology and no inflammatory response,confirming biocompatibility.ConclusionsThis novel codelivery system combining microcrystals and porous microspheres achieves sustained dual-drug release,enhances therapeutic efficacy,and offers a promising strategy for managing hearing loss via intratympanic administration.展开更多
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 chromat...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.展开更多
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 poison...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.展开更多
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...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.展开更多
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...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.展开更多
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-i...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.展开更多
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 (...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).展开更多
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-Dawle...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.展开更多
We here report a non-gene therapy anti-tumor nanoparticles(I3C@cLANPs)based PTEN by loading indole-3-methanol(I3C)into the cross-linked lipoic acid nanoparticles(cLANPs)for triple-negative breast cancer(TNBC)treatment...We here report a non-gene therapy anti-tumor nanoparticles(I3C@cLANPs)based PTEN by loading indole-3-methanol(I3C)into the cross-linked lipoic acid nanoparticles(cLANPs)for triple-negative breast cancer(TNBC)treatment.I3C is a PTEN-specific natural activator while the poor PTEN-activation effi-ciency impedes its ability to achieve the PTEN-mediated tumor therapy.Due to the structural homology of lipoic acid(LA),the cLANPs hold not only LA-like anticancer activity but also PTEN-activation proper-ties,which would synergistically potentiate the PTEN-activation efficiency.The in vitro and in vivo data showed that PTEN expression in the I3C@cLANPs group was 2.1 and 2.8 times higher than that of I3C,respectively.In antitumor evaluation based on the 4T1 tumor-bearing mice showed a tumor inhibitory rate(TIR)of 78.4%at the I3C usage of 20 mg kg^(–1),54.5%higher than that of I3C alone and 19.7%higher than that of first-line chemotherapy drug Doxorubicin hydrochloride(DOX).Thus,the I3C@cLANPs could address the low activation efficiency in the PTEN-mediated tumor strategy and avoid the risks of gene therapy,holding a good prospect for TNBC and related cancer treatment.展开更多
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 dia...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.展开更多
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 f...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.展开更多
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 stabili...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 ℃.展开更多
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 l...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 H<sub>3</sub>PO<sub>4</sub>): 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.展开更多
Objective: to evaluate the efficacy and safety of duloxetine combined with lipoic acid in the clinical treatment of diabetic peripheral neuralgia. Methods: according to the principle of grouping and the difference of ...Objective: to evaluate the efficacy and safety of duloxetine combined with lipoic acid in the clinical treatment of diabetic peripheral neuralgia. Methods: according to the principle of grouping and the difference of treatment schemes, 150 symptomatic cases were divided into two study groups: one was the control group, n75, treated with lipoic acid alone, and the other was the observation group, n75, treated with lipoic acid and duloxetine together. The nerve conduction velocity, pain, clinical effects, adverse reactions and quality of life were analyzed and compared. Results: the nerve conduction velocity in the observation group was higher after treatment (in terms of pain, no matter in terms of score, frequency or duration, the observation group was better than the control group (P<0.05);the total effective rate in the observation group was higher than that in the control group (P<0.05);the incidence of adverse reactions was similar between the two groups (P>0.05);finally, the quality of life of the observation group was at a higher level after treatment (P<0.05). Conclusion: duoxetine combined with lipoic acid can effectively treat diabetic peripheral neuralgia with high safety.展开更多
Objective: to investigate the effect of lipoic acid on the expression of serum heme oxygenase-1 and inflammatory factors in patients with DN. Methods: 80 diabetic nephropathy patients in our hospital were selected as ...Objective: to investigate the effect of lipoic acid on the expression of serum heme oxygenase-1 and inflammatory factors in patients with DN. Methods: 80 diabetic nephropathy patients in our hospital were selected as the observation group, and 80 healthy volunteers were selected as the control group. HO-1, IL-2, IL-6 and TNF-α levels were compared. Results: after intervention, the expression of HO-1 mRNA and inflammatory factors in the observation group were compared with those in the control group (P > 0.05). Conclusion: lipoic acid has good therapeutic effect.展开更多
Objective:To determine whether alpha lipoic acid（LA）can effectively protect lenses from hydrogen peroxide（H<sub>2</sub>O<sub>2</sub>）-induced cataract.Methods:Lens from adult Sprague-Dawley...Objective:To determine whether alpha lipoic acid（LA）can effectively protect lenses from hydrogen peroxide（H<sub>2</sub>O<sub>2</sub>）-induced cataract.Methods:Lens from adult Sprague-Dawley rats were cultured in 24-well plates and treated without or with 0.2 mM of H<sub>2</sub>O<sub>2</sub>,0.2 mM of H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> in inducing cataract and apoptosis.Furthermore.0.2 mM ol H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub>.One mM of LA was found to be the most effective. Conclusions:LA can protect lens from H<sub>2</sub>O<sub>2</sub>-induced cataract.LA exerts protective effects through inhibition of lens’ epithelial cell apoptosis and activation of anti-oxidative enzymes.展开更多
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 int...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.展开更多
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 w...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.展开更多
基金supported by CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-026)the Postdoctoral Fellowship Program of CPSF(No.GZC20230313)。
文摘Most anti-tumor agents suffer from systemic non-specific distribution and low aggregation in tumors,which not only decreases the therapeutic efficacy,but also causes systemic toxic side effects in the treatments of tumors.In recent years,the rapid development of nanotechnology has brought new ideas for the application of anti-tumor drugs.Nanomedicines,such as liposomes and micelles,can improve drug targeting and prolong systemic circulation time to promote anti-tumor efficacy and reduce toxic side effects.However,conventional micelles bear the risk of instability and premature drug leaking in the blood circulation.We designed a reduction-responsive core-cross-linked micelle PTX@Fmoc-LA-PEG efficiently encapsulating Paclitaxel(PTX)viaπ-πstacking and hydrophobic interactions of Fmoc and PTX.Moreover,the micelle was further locked based on the cross-linking properties of the disulfide bonds formed by lipoic acid(LA).As expected,the core-cross-linked micelles PTX@Fmoc-LA-PEG remained stable in normal physiological environments,while restoring the normal drug release rate of micelles under the highly reducing environment due to LA unlocking.The blank micelles(Fmoc-LA-PEG)exhibited excellent biocompatibility,while the drug-loaded micelles(PTX@Fmoc-LA-PEG)displayed a remarkable anti-tumor effect in vitro and in vivo experiments.These results suggested that core-cross-linked micelles PTX@FmocLA-PEG have great potential to improve the targeting and stability of anti-tumor drugs.
文摘The trial by Cano Contreras et al examined a proprietary formulation containing Silybum marianum and alpha-lipoic acid(SM-ALA),combined with a Mediter-ranean diet,in patients with metabolic dysfunction-associated steatotic liver disease.While some metabolic benefits were observed,limitations such as the absence of an SM-ALA-only group,the lack of histological data,and a small sam-ple size reduce the validity of the findings.Future research should follow clinical trial standards for pharmacological studies,including phase 1/2 testing,validated outcomes,and transparency.
基金supported by Capital’s Funds for Health Improvement and Research(CFH:2022-2-5072)the Tianjin Natural Science Foundation for Jingjinji Collaboration(23JCZXJC00240)+1 种基金Beijing Natural Science Foundation(J230006)the CAMS Innovation Fund for Medical Science(2021-I2M-1-052).
文摘ObjectiveTo develop a sustained-release codelivery system for intratympanic administration of dexamethasone(DEX)and lipoic acid(LA).MethodsDEX microcrystals(MCs)were prepared via precipitation,while LA-loaded porous PLGA microspheres(LPMPs)were fabricated using a double emulsion–solvent evaporation method.DEX MCs were physically perfused into LPMPs via negative pressure to form a combined system(DEX MCs+LPMPs).Physicochemical properties,in vitro drug release,pharmacokinetics,and biocompatibility were evaluated.Guinea pigs were used for intratympanic injections of DEX MCs,LPMPs,or DEX MCs+LPMPs.ResultsThe DEX MCs+LPMPs system enabled simultaneous release of both drugs,with DEX exhibiting superior pharmacokinetics(sustained perilymph concentrations up to 7 days)compared to DEX MCs alone.LA release from LPMPs demonstrated prolonged kinetics without burst release.SEM confirmed DEX MCs were localized within/on LPMPs and adhered to the round window membrane(RWM).Histological analysis revealed normal cochlear morphology and no inflammatory response,confirming biocompatibility.ConclusionsThis novel codelivery system combining microcrystals and porous microspheres achieves sustained dual-drug release,enhances therapeutic efficacy,and offers a promising strategy for managing hearing loss via intratympanic administration.
基金Youth Fund of the 2nd Hospital of Shandong University(Grant No.Y2013010075)
文摘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.
基金supported by a grant from the National Natural Science Foundation project of China(30671783)
文摘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.
基金This work was supported in part by the Central Research Committee (CRC) Grant of SIU School of Medicine.
文摘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.
基金supported by grants from the State Key Program of National Natural Science of China (No. 30730094)the National Science & Technology Pillar Program during the Eleventh Five-year Plan Period (No. 2007BAI18B13)
文摘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.
基金supported by Science Research Project from the Education Department of Liaoning Province,No.L2010271
文摘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.
基金Supported by the National Natural Science Foundation of Tianjin (No. 09JCZDJC25700, 12JCZDJC29600 and KJXH2011-11)
文摘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).
基金supported by the National Natural Science Foundation of P.R.China( No .30800790and No .30430520)the National Transgenic Major Project (2009ZX08009-116B)Doctoral Program Foundation of Institutions of High-er Education of China (No .200800191018)
文摘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.
基金supported by the National Natural Science Foundation of China(Nos.22275129 and 21975165)the Innovative Research Team Program of Sichuan Province(No.2021JDTD0015)the Sichuan University Postdoctoral Interdisciplinary Innovation Fund(No.2022SCU12106).
文摘We here report a non-gene therapy anti-tumor nanoparticles(I3C@cLANPs)based PTEN by loading indole-3-methanol(I3C)into the cross-linked lipoic acid nanoparticles(cLANPs)for triple-negative breast cancer(TNBC)treatment.I3C is a PTEN-specific natural activator while the poor PTEN-activation effi-ciency impedes its ability to achieve the PTEN-mediated tumor therapy.Due to the structural homology of lipoic acid(LA),the cLANPs hold not only LA-like anticancer activity but also PTEN-activation proper-ties,which would synergistically potentiate the PTEN-activation efficiency.The in vitro and in vivo data showed that PTEN expression in the I3C@cLANPs group was 2.1 and 2.8 times higher than that of I3C,respectively.In antitumor evaluation based on the 4T1 tumor-bearing mice showed a tumor inhibitory rate(TIR)of 78.4%at the I3C usage of 20 mg kg^(–1),54.5%higher than that of I3C alone and 19.7%higher than that of first-line chemotherapy drug Doxorubicin hydrochloride(DOX).Thus,the I3C@cLANPs could address the low activation efficiency in the PTEN-mediated tumor strategy and avoid the risks of gene therapy,holding a good prospect for TNBC and related cancer treatment.
文摘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.
基金National Key Research and Development Projects:Demonstration Study on Early Identification(No.2018YFC2002500)。
文摘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.
基金Supported by International Scientific Cooperation Project of China (No.2008DFB50060)Suzhou Innovation Funds of High-Tech Enterprise (No.SG0958)
文摘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 ℃.
文摘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 H<sub>3</sub>PO<sub>4</sub>): 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.
文摘Objective: to evaluate the efficacy and safety of duloxetine combined with lipoic acid in the clinical treatment of diabetic peripheral neuralgia. Methods: according to the principle of grouping and the difference of treatment schemes, 150 symptomatic cases were divided into two study groups: one was the control group, n75, treated with lipoic acid alone, and the other was the observation group, n75, treated with lipoic acid and duloxetine together. The nerve conduction velocity, pain, clinical effects, adverse reactions and quality of life were analyzed and compared. Results: the nerve conduction velocity in the observation group was higher after treatment (in terms of pain, no matter in terms of score, frequency or duration, the observation group was better than the control group (P<0.05);the total effective rate in the observation group was higher than that in the control group (P<0.05);the incidence of adverse reactions was similar between the two groups (P>0.05);finally, the quality of life of the observation group was at a higher level after treatment (P<0.05). Conclusion: duoxetine combined with lipoic acid can effectively treat diabetic peripheral neuralgia with high safety.
文摘Objective: to investigate the effect of lipoic acid on the expression of serum heme oxygenase-1 and inflammatory factors in patients with DN. Methods: 80 diabetic nephropathy patients in our hospital were selected as the observation group, and 80 healthy volunteers were selected as the control group. HO-1, IL-2, IL-6 and TNF-α levels were compared. Results: after intervention, the expression of HO-1 mRNA and inflammatory factors in the observation group were compared with those in the control group (P > 0.05). Conclusion: lipoic acid has good therapeutic effect.
文摘Objective:To determine whether alpha lipoic acid（LA）can effectively protect lenses from hydrogen peroxide（H<sub>2</sub>O<sub>2</sub>）-induced cataract.Methods:Lens from adult Sprague-Dawley rats were cultured in 24-well plates and treated without or with 0.2 mM of H<sub>2</sub>O<sub>2</sub>,0.2 mM of H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> in inducing cataract and apoptosis.Furthermore.0.2 mM ol H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub>.One mM of LA was found to be the most effective. Conclusions:LA can protect lens from H<sub>2</sub>O<sub>2</sub>-induced cataract.LA exerts protective effects through inhibition of lens’ epithelial cell apoptosis and activation of anti-oxidative enzymes.
基金Supported by the Guangzhou Science and Technology Foundation of Guangdong Province (No.2014J4100035 No.2014KP000071)
文摘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.
基金Supported by Grants from the National Science Council of the ROC, No. NSC98-2320-B-016-011 MY3,CMNDMC 100-05 and TSGH-C100-011-015-S03
文摘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.
