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.

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.

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).

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.

Effects of alprostadil combined with lipoic acid on clinical efficacy, hemodynamics, fibronectin and plasma D-dimer in elderly patients with type 2 diabetic foot

ObjectiveTo investigate the effects of alprostadil combined with lipoic acid on clinical efficacy,hemodynamics,fibronectin and plasma D-dimer in elderly patients with type 2 diabetic foot.Methods Ninety-six elderly patients with type 2 diabetic foot hospitalized in Department of Endocrinology,Xining First People's Hospital from January 2017 to June 2019 were selected as the study subjects.They were divided into control group(48 cases)and case group(48 cases)by random number table method.The control group was treated with lipoic acid,and the case group was treated with Alprostadil for injection on the basis of the control group.The clinical efficacy,clinical symptom score,ulcer healing,hemodynamics of dorsal artery of foot,fibronectin and plasma D-two dimer in two groups were observed.Results The total effective rate of the case group was 95.83%,which was significantly higher than that of the control group(83.33%).The difference was statistically significant(P<0.05).After treatment,the pain,swelling,claudication,numbness score,ulcer area,wound PH value,plasma D-dimer level of the two groups were lower than those before treatment,and the oxygen partial pressure,blood flow velocity,vascular diameter,Resistance index(RI),pulsation index(PI)and fibronectin levels of the two groups were higher than those before treatment,the difference was statistically significant(P<0.05).The improvement of clinical efficacy,ulcer healing,dorsal pedal artery hemodynamics,fibronectin and plasma D-dimer levels in the case group were significantly better than those in the control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).ConclusionsAlprostadil combined with lipoic acid has significant clinical effect on elderly patients with type 2 diabetic foot.It can correct the abnormal hemodynamics of dorsal pedal artery,promote the healing of foot ulcer,increase the content of fibronectin ulcer tissue,reduce the level of plasma D-dimer and improve the high coagulation state.It has high efficiency and safety.It is worthy of clinical application.Further promotion.

Effects of lipoic acid on the activities of fibrinase, antioxidant enzymes and related factors in patients with type 2 diabetic foot

Objective:To investigate the effects of lipoic acid on the activities of fibrinase, antioxidant enzymes and related factors in patients with type 2 diabetic foot.Methods: 120 patients with type 2 diabetic foot treated in the Department of Endocrinology and Metabolism in our hospital from March 2015 to March 2018 were collected and randomly divided into control group and observation group, 60 cases in each group. The patients in control group were treated with alprostadil, and the patients in observation group were treated with lipoic acid combined with alprostadil. Before and after treatment, the levels of plasminogen activator, fibrinopeptide A, plasminogen activator inhibitor-1, superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT), Toll-like receptor 2 (TLR2), Toll-like receptor 9 (TLR9), vascular cell adhesion molecule-1 (VCAM-1), matrix metalloproteinase-9 (MMP-9) and homocysteine (Hcy) of patients in the two groups were detected and compared.Results: After treatment, the levels of plasminogen activator, SOD, GSH-PX and CAT of patients in the control group and the observation group were significantly increased. The levels of fibrinogen A and plasminogen activator inhibitor -1 of patients in the control group and the observation group were significantly decreased. The changes of the above indexes of patients in the observation group were more obvious than those in the control group (P<0.05). The levels of TLR2, TLR9, VCAM-1, MMP-9 and Hcy in the serum of patients in the control group and the observation group were significantly decreased. The down-regulation of these factors of patients in the observation group was more obvious than that in the control group (P<0.05).Conclusion:Lipoic acid combined with alprostadil in the treatment of type 2 diabetes mellitus disease can significantly enhance the activity of fibrinolytic enzymes and antioxidant capacity, alleviate inflammation, and it has a good clinical effect.

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.

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.

Effect of adjuvant lipoic acid therapy on the systemic oxidative stress response and local inflammatory response in patients with diabetic foot

Objective: To study the effect of adjuvant lipoic acid therapy on the systemic oxidative stress response and local inflammatory response in patients with diabetic foot. Methods: Patients with diabetic foot who received conservative treatment in Qinzhou Traditional Chinese and Western Medicine Hospital of Guangxi Province between June 2014 and April 2017 were selected as the research subjects and randomly divided into the lipoic acid group who received lipoic acid combined with conventional therapy and the control group who received conventional therapy. The contents of oxidative stress indexes in serum were measured before treatment and 1 week after treatment;the contents of inflammatory response indexes and apoptosis indexes in wound tissue were determined 1 week after treatment. Results: 1 week after treatment, serum SOD, GPx and CAT contents of both groups of patients were higher than those before treatmentwhereas MDA and AOPP contents were significantly lower than those before treatment, and serum SOD, GPx and CAT contents of lipoic acid group were significantly higher than those of control group whereas MDA and AOPP contents were significantly lower than those control group;1 week after treatment, TLR2, TLR9, ICAM1, IL-1, IL-6, TNF-α, AIF, Bax, Fas, FasL and Caspase-3 contents in the wound of lipoic acid group were significantly lower than those of control group whereas Bcl-2 content was significantly higher than that of control group. Conclusion: Adjuvant lipoic acid treatment of diabetic foot can reduce the systemic oxidative stress response and local inflammatory response.

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.

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.

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.

LA-ICP-MS测定单颗粒氨基膦酸螯合树脂中的铀分布

以利用氨基膦酸螯合树脂从湿法磷酸(WPA)中回收铀为研究背景,对单颗粒氨基膦酸螯合树脂中铀分布进行研究,得到以下结论:确定激光剥蚀电感耦合等离子体质谱仪(LA-ICP-MS)最佳的激光频率为6 Hz、束斑直径为44μm、能量密度为6 J/cm^(2)。选择吸附饱和的树脂和洗脱完全的树脂分别作为吸附和淋洗过程的外标,对其进行均匀性测试,吸附饱和树脂中铀含量的相对标准偏差为3.87%(n=9),洗脱完全树脂中铀含量的相对标准偏差为3.52%(n=9),均一性良好。利用LA-ICP-MS对氨基膦酸螯合树脂中的铀进行原位微区分析,结果表明:铀在树脂上的吸附过程是由外向内逐渐完成,淋洗过程是由外向内逐渐完成,树脂内外铀浓度逐渐均匀统一,最终达到吸附饱和和淋洗完全。

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.

Inducement of Salicylic Acid in Cucumber Cotyledons by Neodymium and Lanthanum

The cotyledons of cucumber were used to investigate the effects of Nd^3＋ and La^3＋ on physiological characters in respect of plant resistance. The cucumber cotyledons were sprayed with 15 μg · ml^-1· Nd^3＋ and La^3＋, and the changers on salicylic acid （SA） and SA 2-O-β-glucoside （SAG） contents, the generation of ·O2^-, and β-1,3-glucanase and chitinase activities were measured. The results demonstrated that the yields of endogenous SA and SAG in cucumber cotyledons were enhanced significantly in a short time in response to Nd^3＋ and La^3＋ treatments. At 3 h after La^3＋ treatment, the levels of SA and SAG reached the maximum, with 4.3 and 3.3-fold of that in control （CK）, respectively. At 12 h after Nd3＋ treatment, the contents of SA and SAG reached peak levels, increased by 4.5 and 3.0-fold of that in control （CK）, respec- tively. These two components were kept in a higher level up to 72 h after treatment. The generation rate of · O2^- increased gradually in the treatments of Nd^3＋ or La^3＋, and then decreased in cucumber at 12 h. β-1,3-glucanase activity reached peak at 3 h, while chitinase activity reached peak at 12 h, and then both decreased gradually in Nd^3＋ or La^3＋ treatments. At 72 h after treatment, activities of β-1, 3-glucanase and chitinase increased by about 30% and 50%, as compared with CK. Therefore, these results suggested that both Nd^3＋ and La^3＋ could increase the contents of endogenous SA and its related factors which induce plant resistance through the signal pathway of the salicylic acid.

Effect of Lanthanum on Acid Secretion from Isolated Mouse Stomach in Vitro

To explore the effect and the mechanism of La^(3+) on gastric acid secretion (GAS) of isolated mouse stomach with perfused lumen, 12 cm H_2O column intragastric pressure-provided, whole stomach preparations from mice were incubated in buffer at 37 ℃ in vitro, and perfusate was measured for pH with a pHS-3 type pH meter. The results show that La^(3+) (0.41～820×10^(-6) mol·L^(-1)) significantly promotes GAS in a concentration-dependant manner. Proglutamine, a blocker of gastrin receptor, potently inhibits GAS, and it may block the promotive effect of La^(3+) on GAS, and this effect increases with the increase of proglutamin concentration. Cimetidine, a blocker of histamine H_2 receptor, also potently inhibits GAS, and blocks the promotive effect of La^(3+) on GAS in the same manner with proglutamine. These results suggest that La^(3+) promotes GAS in isolated stomach possibly by stimulating the releases of gastrin from G cell and Histamine from ECL cell or by activating the gastrin receptors and Histamine H_2 receptors on the parietal cell, thereby accelerating the acid secretion of parietal cells in stomach.

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.

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.

氨基酸螯合镧(La(Ⅲ)-AA)对模拟酸雨胁迫下三种作物生理指标的影响

酸雨对农业生态系统中作物的影响,攸关粮食安全,抗酸(雨)减灾研究迫在眉睫.本文采用模拟酸雨污染盆栽实验方法,研究一种新型氨基酸螯合镧对酸雨胁迫下玉米、水稻、小麦等8项生理指标的影响.结果表明,与对照组相比预施氨基酸螯合镧能有效降低酸雨对3种作物叶片质膜透性(45.95%—54.22%)、超氧阴离子自由基产生速率(28.44%—42.31%)、丙二醛含量(31.03%—38.71%)、脯氨酸(36.23%—47.17%)含量及过氧化物酶活性(48.3%—57.92%)的影响,提高过氧化氢酶活性(29.43%—78.61%)、叶绿素含量(7.89%—18.76%)和氮代谢强度(21.37%—60.63%).由此可见,氨基酸螯合镧对酸雨胁迫下,作物的过氧化损伤具有一定防护效应,预喷氨基酸螯合镧可在一定程度上减轻酸雨污染对作物的伤害.

Solvent Extraction of Lanthanum Ion from Chloride Medium by Di-(2-ethylhexyl) Phosphoric Acid with a Complexing Method

Solvent extraction experiments of La(III) with di-(2-ethylhexyl)phosphoric acid (P204) from chloride solution in the presence of a complexing agent (lactic acid) have been performed. The effective separation factors can be achieved when the complexing agent is added to the aqueous phase of the extraction system. The complexing agent lactic acid can be effectively recycled using tributyl phosphate (TBP) as extractant, by the use of a countercurrent extraction process, and the chemical oxygen demand (COD) value in the raffinate is 57.7 mg/L, which meets the emission standards of pollutants from rare earths industry. Thus, the simple and environment-friendly complexing method has been proved to be an effective strategy for separating light rare earths, and provides a positive influence on the purification of La(III).