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.

Protective Effects of α-Lipoic Acid on Vascular Oxidative Stress in Rats with Hyperuricemia

The aim of the present study was to observe the protective effects of α-lipoic acid(ALA)on vascular injury in rats with hyperuricemia(HUA).The ALA treatment groups(10,30 and 90 mg/kg,respectively)were administered with ALA via gavage for 2 weeks.Subsequently,the levels of blood urea nitrogen(BUN),creatinine(CREA),uric acid(UA),total cholesterol(TC),high density lipoprotein-C(HDL-C)and low density lipoprotein-C(LDL-C)were measured;the activities of glutathione peroxidase(GSH-Px),catalase(CAT),malonaldehyde(MDA),superoxide dismutase(SOD)and xanthine oxidase(XOD)were also determined.The thoracic aorta of rats in each experimental group was observed under a light microscope;ultrastructural analysis was performed.SOD and CAT protein contents were investigated by Western blotting.The results revealed that:i)Compared with the model group,the levels of UA were decreased in the ALA groups and the levels of BUN,CREA,TC,and LDL-C decreased in the 30 and 90 mg/kg ALA groups(P<0.05);ii)compared with the model group,the activities of GSH-Px,SOD and XOD were increased and the levels of MDA were reduced in the 90 mg/kg ALA group (P<0.05);and iii)in the model and 10 mg/kg ALA groups,edema and shedding were observed in endothelial cells.Compared with the model and 10 mg/kg ALA groups,the 30 and 90 mg/kg ALA groups exhibited fewer swollen endothelial cells.In summary,the results of the present study indicated that HUA resulted in vascular oxidative stress injury and decreased the activity of antioxidative enzymes,which leads to endothelial cell damage and vascular lesions.ALA may serve as a therapeutic agent for the treatment of HUA-induced endothelial dysfunction.

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.

Influence ofα-Lipoic acid adjuvant therapy on sugar metabolism,peripheral nerve conduction velocity and oxidative stress in patients with diabetic peripheral neuropathy

Objective: To explore the influence of α-Lipoic acid adjuvant therapy on glucose metabolism, peripheral nerve conduction velocity and oxidative stress in patients with diabetic peripheral neuropathy. Methods: A total of 92 cases of patients with diabetic peripheral neuropathy were divided into observation group and control group according to the odd and even admission number, 46 cases in each group. All patients were given the conventional treatment, on this basis, patients in control group were given orally Pancreatic Kinionoge, patients in observation group were given α-Lipoic acid intravenous injection. They were treated for 14 d. The following indicators were observed in two groups before and after treatment: glucose metabolic index: fasting blood glucose (FBG), 2 h postprandial blood glucose (2hPBG) and glycosylated hemoglobin (HbA1c);peripheral nerve conduction velocity, median nerve, sensory nerve conduction velocity of nervus peroneus communis (MCV) and motor nerve conduction velocity (SCV), ankle arm index (ABI) and inner diameter of lower limb artery (femoral artery, dorsalis pedis artery, popliteal artery), oxidative stress indicators: superoxide dismutase (SOD) and malondialdehyde (MDA). Results: Compared with before treatment, the FBG, 2hPBG, HbA1c level in two groups after treatment were significantly reduced, but the difference of intergroup after treatment was no statistical significance;MCV and SCV of median nerve and nervus peroneus communis was increased significantly than control group after treatment, moreover MCV and SCV of median nerve and nervus peroneus communis in observation group were higher than control group after treatment, the difference was significant. After treatment, ABI and femoral artery, dorsalis pedis arteries, popliteal artery inner diameter in two groups were increased significantly, moreover after treatment the above level in observation group was obviously higher than control group, there was significant difference. After treatment, the MDA in observation group were reduced significantly and SOD level increased significantly, difference was statistically significant compared with before treatment and control group after the treatment;The difference in control group compared between before treatment and after treatment had no statistical significance. Conclusion: Diabetic peripheral neuropathy treated adjuvantly by α-Lipoic acid can significantly improve lower limb blood supply, improve the peripheral nerve conduction velocity, reduce level of oxidative stress, the effect on glucose metabolism still need long course of observation.

Efficacy evaluation of high-frequency ultrasound in the treatment of diabetic peripheral neuropathy with α-lipoic acid combined with traditional Chinese medicine package treatment

Objective:To use high-frequency ultrasound to evaluate the efficacy ofα-lipoic acid combined with traditional Chinese medicine in the treatment of diabetic peripheral neuropathy(DPN),so as to provide a basis for clinical medication and evaluation of therapeutic effect.Methods:From December 2018 to December 2019,110 patients with DPN who met the inclusion and exclusion criteria were divided into observation group and control group according to different treatment plans.The control group was treated withα-lipoic acid,and the observation group was treated withα-lipoic acid combined with traditional Chinese medicine encapsulation treatment,and used high-frequency ultrasound,nerve conduction velocity and serological examination to comprehensively evaluate the effectiveness of the two treatment methods.Results:The mean amplitude of glycemic excursions(MAGE)value of the observation group and the control group after treatment was significantly lower than before treatment(P<0.05);After treatment,the SCV of the ulnar nerve,median nerve,and common peroneal nerve in the two groups was significantly faster than before treatment(P<0.05).Similar to SCV,the MCV of the three nerves measured after treatment in the two groups was significantly faster than before treatment(P<0.05).Compared between the groups after treatment,the three kinds of nerve SCV and MCV in the observation group were significantly faster than those in the control group(P<0.05).The cross-sectional area(CSA)value of the ulnar nerve,median nerve and common peroneal nerve in the observation group after treatment was significantly lower than before treatment(P<0.05).Compared with the control group after treatment,the three nerves CSA in the observation group was significantly lower than that in the control group(P<0.05).Abnormal ultrasound performance:The proportion of abnormal ultrasound performances of the ulnar nerve,median nerve,and common peroneal nerve in the observation group after treatment was significantly lower than before treatment(P<0.05).The composition ratio of internal echo reduction and ambiguity in the observation group after three nerve treatments was significantly lower than that in the control group after treatment(P<0.05).In the correlation analysis,the three kinds of nerve CSA before and after treatment were negatively correlated with SCV and amplitude(P<0.05),and positively correlated with latency(P<0.05).Conclusion:The combination ofα-lipoic acid and Chinese medicine encapsulation technology has a good effect on the treatment and repair of DPN nerve damage,and can be routinely applied in clinical treatment.High-frequency ultrasound can intuitively observe changes in peripheral nerves and can be used to evaluate the prognosis of DPN.

Effects of α-lipoic acid on oxidative stress, vascular endothelium function and renal function in patients with diabetic nephropathy

Objective:To investigate the effects ofα-lipoic acid on oxidative stress, vascular endothelium function and renal function in diabetic nephropathy patients.Methods: According to random data table method, a total of 80 patients with diabetic nephropathy from September 2016 to August 2017 were divided into observation group and control group (n=40). The patients of control group were treated with routine therapy while the patients of observation group were given intravenous infusion ofα-lipoic acid on the basis of conventional therapy. The levels of oxidative stress, vascular endothelium function and renal function changes were compared between the two groups before and after the treatment.Results:The levels of SOD, MDA, NO, ET-1, RBP and CysC in the two groups before treatment were not statistically significant. Compared with the levels before treatment, the level of SOD in the observation group was significantly increased and the level of MDA was significantly decreased;the level of SOD in the observation group was significantly higher than that in the control group, and the level of MDA was significantly lower than that of the control group;the above differences were statistically significant. The levels of SOD and MDA had no significant changes in the control group before and after treatment. After treatment, the levels of ET-1, RBP and CysC in the two groups were significantly lower than those in the same group before treatment, and the observation group levels were significantly lower than those in the control group;the levels of NO in the two groups after treatment were significantly higher than those in the same group before treatment, and the observation group was significantly higher than that of the control group;the above differences were statistically significant.Conclusions: On the basis of conventional treatment, combining withα-lipoic acid can better reduce the level of oxidative stress, improve vascular endothelial function, renal function in patients with diabetic nephropathy, which has an important clinical value.

Effect of α-lipoic acid combined with nerve growth factor on bone metabolism, oxidative stress and nerve conduction function after femoral fracture surgery

Objective: To discuss the effect of α-lipoic acid combined with nerve growth factor on bone metabolism, oxidative stress and nerve conduction function after femoral fracture surgery. Methods: A total of 110 patients with femoral fracture who received surgical treatment in the hospital between January 2015 and January 2017 were collected and divided into the control group (n=55) and study group (n=55) by random number table. Control group received postoperative nerve growth factor therapy, and study group received postoperative α-lipoic acid combined with nerve growth factor therapy. The differences in the contents of bone metabolism and oxidative stress indexes as well as the levels of nerve conduction function indexes were compared between the two groups before and after treatment. Results: Before treatment, the differences in the contents of bone metabolism and oxidative stress indexes as well as the levels of nerve conduction function indexes were not statistically significant between the two groups. After treatment, serum bone metabolism indexes BGP and PⅠNP contents of study group were higher than those of control group while CTX-Ⅰ and TRAP contents were lower than those of control group;serum oxidative stress indexes TAC, CAT and SOD contents of study group were higher than those of control group while MDA content was lower than that of control group;limb nerve conduction velocity SCV and MCV levels of study group were higher than those of control group. Conclusion: α-lipoic acid combined with nerve growth factor therapy after femoral fracture surgery can effectively balance osteoblast/osteoclast activity, reduce oxidative stress and improve limb nerve conduction velocity.

α-硫辛酸辅助基础胰岛素治疗2型糖尿病临床疗效研究

目的观察并探讨α-硫辛酸辅助基础胰岛素治疗2型糖尿病临床作用。方法选取我院于2015年1月至2016年3月收治的100例2型糖尿病患者作为研究对象,随机分为实验组与对照组,对照组患者则采取常规胰岛素降糖药物治疗,实验组患者在此基础上加用α-硫辛酸抗氧化治疗,比较两组治疗前后空腹血糖、血脂指标、氧化应激等指标变化,评估两组治疗效果及不良反应。结果治疗4周后,实验组空腹血糖显著低于对照组(6.18±0.88 vs.6.71±1.02mmol/L),差异具有统计学意义(P<0.05);两组治疗后血脂指标差异均无统计学意义(P>0.05);实验组患者治疗后尿蛋白排泄率、血浆内皮素-1、一氧化氮水平(125.84±15.51 mg/24h、57.13±10.21ng/L、33.53±5.11μmol/L)显著低于对照组(146.12±18.13 mg/24h、72.25±12.87 ng/L、40.79±7.32μmol/L);实验组治疗后丙二醛含量显著低于对照组(3.28±1.09μmol/L vs.4.48±1.13μmol/L),而超氧化物歧化酶含量显著高于对照组(44.54±7.48U/mL vs.32.57±6.94 U/mL),差异具有统计学意义(P<0.05);所有患者在接受治疗过程中未发生不良反应,实验组治疗后临床有效率(94.12%vs.77.55%)显著高于对照组(P<0.05)。结论氧化应激在2型糖尿病发生发展中具有重要作用,α-硫辛酸辅助基础胰岛素治疗2型糖尿病可以有效的改善患者的病情。

Copper-mediated chemodynamic therapy with ultra-low copper consumption by doping cupric ion on cross-linked(R)-(+)-lipoic acid nanoparticles

Cu-mediated chemodynamic therapy(CDT)has attracted prominent attention owing to its advantages of pH independence and high efficiency comparing to Fe-mediated CDT,while the application of Cu-based CDT agents was impeded due to the high copper consumption caused by the metabolism loss of copper and the resultant potential toxicity.Herein,we developed a new copper-mediated CDT agent with extremely low Cu usage by anchoring copper on cross-linked lipoic acid nanoparticles(Cu@cLAs).After endocytosis into tumor cells,the Cu@cLAs were dissociated into LA and dihydrolipoic acid(DHLA)(reduced form of LA)and released Cu^(2+)and Cu+(oxidized form of Cu^(2+)),the two redox couples recycled each other in cells to achieve the efficient killing of cancer cells by delaying metabolic loss and increasing the ROS level of tumor cells.The self-recycling was confirmed in cells by the sustained high Cu/DHLA content and persistent ROS generation process.The antitumor study based on the MCF-7/R nude mice gave the Cu@cLAs a tumor inhibitory rate up to 77.9%at the copper of 0.05 mg kg^(−1),the first dosage reported so far lower than that of normal serum copper(0.83±0.21 mg kg^(−1)).This work provides not only a new promising clinical strategy for the copper excessive use in copper-mediated CDT,but also gives a clue for other metal mediated disease therapies with the high metal consumption.

Quantitative determination of low molecular weight antioxidants and their effects on different antioxidants in chicken blood plasma

Antioxidants in the body are in balance, and form a network that protects living organisms against oxidative stress. To prove this hypothesis, we developed suitable methods for assessing the amount of antioxidants and their antioxidant activity in the chickens’ plasma, which enable us to explain the overall anti-oxidant status of the animals during the controlled industrial raise. The effects of exogenous coenzyme Q10, and α-lipoic acid on the reduction of oxidative stress in the animal body were assessed. The physical and the health conditions of chickens during the raising period of 40 days were followed. The benefits of additives were estimated through the measured concentrations of selected low molecular weight antioxi-dants (coenzyme Q10, α-lipoic acid, α-tocopherol, lutein and zeaxathin) and antioxidant enzymes (super-oxide dismutase, glutathione reductase), cholesterol and glucose in plasma and measurements of total antioxidant capacity. Quantitative analyses of selected substances were done with different chromatographic, spectroscopic and electrometric methods. The addition of antioxidants has positive effects on the acts of antioxidant network.

α-Lipoic Acid Exerts Its Antiviral Effect against Viral Hemorrhagic Septicemia Virus(VHSV) by Promoting Upregulation of Antiviral Genes and Suppressing VHSV-Induced Oxidative Stress

Viral hemorrhagic septicemia virus(VHSV), belonging to the genus Novirhabdovirus, Rhabdoviridae family, is a causative agent of high mortality in fish and has caused significant losses to the aquaculture industry. Currently, no effective vaccines, Food and Drug Administration-approved inhibitors, or other therapeutic intervention options are available against VHSV. α-Lipoic Acid(LA), a potent antioxidant, has been proposed to have antiviral effects against different viruses. In this study, LA(CC_(50)= 472.6 lmol/L) was repurposed to exhibit antiviral activity against VHSV. In fathead minnow cells,LA significantly increased the cell viability post-VHSV infection(EC_(50)= 42.7 lmol/L), and exerted a dose-dependent inhibitory effect on VHSV induced-plaque, cytopathic effects, and VHSV glycoprotein expression. The time-of-addition assay suggested that the antiviral activity of LA occurred at viral replication stage. Survival assay revealed that LA could significantly upregulated the survival rate of VHSV-infected largemouth bass in both co-injection(38.095% vs. 1.887%,P < 0.01) and post-injection manner(38.813% vs. 8.696%, P < 0.01) compared with the control group. Additional comparative transcriptome and q RT-PCR analysis revealed LA treatment upregulated the expression of several antiviral genes, such as IRF7, Viperin, and ISG15. Moreover, LA treatment reduced VHSV-induced reactive oxygen species production in addition to Nrf2 and SOD1 expression. Taken together, these data demonstrated that LA suppressed VHSV replication by inducing antiviral genes expression and reducing VHSV-induced oxidative stress. These results suggest a new direction in the development of potential antiviral candidate drugs against VHSV infection.