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
Objective:To investigate the effect of alpha-lipoic acid(ALA)supplementation on systolic blood pressure(SBP),renal oxidant-antioxidant status and renal damage in spontaneously hypertensive rats(SHR)and SHR administere...Objective:To investigate the effect of alpha-lipoic acid(ALA)supplementation on systolic blood pressure(SBP),renal oxidant-antioxidant status and renal damage in spontaneously hypertensive rats(SHR)and SHR administered with Nω-nitro-L-arginine methyl ester(L-NAME).Methods:Male rats were divided into four groups(SHR,SHR+ALA,SHR+L-NAME,SHR+ALA+L-NAME).The respective group of rats was administered with ALA(100 mg/kg/day)from age 4 weeks to 28 weeks and L-NAME(25 mg/kg/day)from age 16 weeks to 28 weeks.SBP was measured every two weeks and twenty four hour urine was collected at 4 weeks,16 weeks and 28 weeks for estimation of protein,creatinine and N-acetyl-e end of 28 weeks,rats were sacrificed and blood and kidneys colα-Dglucosaminidase.At thlected for assessment of blood creatinine,kidney thiobarbituric acid reactive substances,protein carbonyls,superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase,glutathione S-transferase,glutathione disulfide,glutathione,total antioxidant status and nitric oxide as well as histopathological examination.Results:ALA supplementation significantly reduced SBP of SHR and SHR+L-NAME rats when compared to their respective non-supplemented groups.Renal oxidant status markers including thiobarbituric acid reactive substances and protein carbonyls were significantly reduced on SHR and SHR+L-NAME rats supplemented with ALA at 28 weeks as well as ALA supplementation significantly increased renal antioxidants including superoxide dismutase,catalase,glutathione peroxidase,glutathione S-transferase,glutathione and glutathione/glutathione disulfide ratio at 28 weeks.No significant change in nitric oxide levels was observed between the ALA supplemented and non-supplemented groups.Renal dysfunction was ameliorated on ALA supplementation as evidenced by significant reduction in urine protein levels,N-acetyl-α-D-glucosaminidase activity and significant increase of creatinine clearance in SHR and SHR+L-NAME at 28 weeks.Renal histopathological examination showed that ALA supplementation prevented vascular damage in SHR and ameliorated glomerular damage in SHR+L-NAME at 28 weeks.Conclusions:ALA has hypotensive and renoprotective effects on both SHR and SHR+LNAME,which could be due to its ability to ameliorate oxidative stress in the kidneys.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
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:Relevance of cardiac autonomic neuropathy has not been fully recognized and there is no standardized treatment protocol.Aim:To evaluate the effects of alpha-lipoic acid on the beat-to-beat vectorcardiographi...Objective:Relevance of cardiac autonomic neuropathy has not been fully recognized and there is no standardized treatment protocol.Aim:To evaluate the effects of alpha-lipoic acid on the beat-to-beat vectorcardiographic parameters,namely spatial QRS-T angle,QT dispersion(QTd)and corrected QT interval(QTc)in type 2 diabetes mellitus persons with cardiac autonomic neuropathy.Research designs and methods:Our study involved 33 persons with definite stage of cardiac autonomic neuropathy and diabetes mellitus type 2,which were assigned to each of two groups:one took standard antihyperglycaemic treatment(n=15,control group)and the other(n=18)in addition to standard therapy-600 mg of alpha-lipoic acid daily for three months.The analysis of vectorcardiographic parameters was performed.Results:It was found out that alpha-lipoic acid contributed to decrease of the vectorcardiographic parameters,namely QRS-T angle,QTd and QTc.Conclusions:The positive influences of alpha-lipoic acid suggest the usefulness of its prescription to type 2 diabetes mellitus persons with definite stage of cardiac autonomic neuropathy.The efficacy of alpha-lipoic acid is the result of its direct effect on the parameters of vectorcardiography.展开更多
Background Cardiac failure is a leading cause of the mortality of diabetic patients. In part this is due to a specific cardiomyopathy, referred to as diabetic cardiomyopathy. Oxidative stress is widely considered to b...Background Cardiac failure is a leading cause of the mortality of diabetic patients. In part this is due to a specific cardiomyopathy, referred to as diabetic cardiomyopathy. Oxidative stress is widely considered to be one of the major factors underlying the pathogenesis of the disease. This study aimed to test whether the antioxidant α-lipoic acid （α-LA） could attenuate mitochondrion-dependent myocardial apoptosis through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy. Methods A rat model of diabetes was induced by a single tail intravenous injection of streptozotocin （STZ） 45 mg/kg. Experimental animals were randomly assigned to 3 groups： normal control （NC）, diabetes （DM） and DM treated with α-LA （α-LA）. The latter group was administered with a-LA （100 mg/kg ip per day）, the remainder received the same volume vehicle. At weeks 4, 8, and 12 after the onset of diabetes, cardiac apoptosis was examined by TUNEL assay. Cardiomyopathy was evaluated by assessment of cardiac structure and function. Oxidative damage was evaluated by the content of malondialdehyde （MDA）, reduced glutathione （GSH） and the activity of manganese superoxide diamutase （Mn-SOD） in the myocardial mitochondria. Expression of caspase-9 and caspase-3 proteins was determined by immunohistochemistry and mitochondrial cytochrome c release was detected by Western blotting Results At 4, 8, and 12 weeks after the onset of diabetes, significant reductions in TUNEL-positive cells, caspase-9,-3 expression, and mitochondrial cytochrome c release were observed in the α-LA group compared to the DM group. In the DM group, the content of MDA in the myocardial mitochondria was significantly increased, and there was a decrease in both the mitochondrial GSH content and the activities of Mn-SOD. They were significantly improved by α-LA treatment. HE staining displayed structural abnormalities in diabetic hearts, while α-LA reversed this structural derangement. The index of cardiac function （±dp/dtmax） in the diabetes group was aggravated progressively from 4 weeks to 12 weeks, but α-LA delayed deterioration of cardiac function （P 〈0.05）. Conclusions Our findings indicate that the antioxidant α-LA can effectively attenuate mitochondria-dependent cardiac apoptosis and exert a protective role against the development of diabetic cardiomyopathy. The ability of α-LA to suppress mitochondrial oxidative damage is concomitant with an enhancement of Mn-SOD activity and an increase in the GSH content of myocardial mitochondria.展开更多
目的用Meta分析对临床使用α-硫辛酸联合甲钴胺治疗糖尿病周围神经病变的方案进行分析,评价其治疗效果。方法利用中国学术期刊全文数据库(CNKI)、万方全文数据库,检索到2008～2012年国内发表的α-硫辛酸联合甲钴胺治疗糖尿病周围神经病...目的用Meta分析对临床使用α-硫辛酸联合甲钴胺治疗糖尿病周围神经病变的方案进行分析,评价其治疗效果。方法利用中国学术期刊全文数据库(CNKI)、万方全文数据库,检索到2008～2012年国内发表的α-硫辛酸联合甲钴胺治疗糖尿病周围神经病变临床试验的相关文献,应用Meta分析软件包Rev Man 5.0对各研究结果进行数据合并,并进行发表偏倚分析。结果共纳入文献12篇,859例糖尿病周围神经病变患者,各研究结果间存在同质性(P=0.85>0.05),α-硫辛酸与甲钴胺治疗联合治疗组总体有效率明显高于对照组[P<0.000 01,(OR=5.30,95%CI:3.59～7.82)]。结论与单独使用甲钴胺相比,采用α-硫辛酸联合甲钴胺的方法治疗糖尿病周围神经病变更加有效。展开更多
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 Short Term Research Grant Scheme(304/PPSP/6131496)provided by Universiti Sains Malaysia.
文摘Objective:To investigate the effect of alpha-lipoic acid(ALA)supplementation on systolic blood pressure(SBP),renal oxidant-antioxidant status and renal damage in spontaneously hypertensive rats(SHR)and SHR administered with Nω-nitro-L-arginine methyl ester(L-NAME).Methods:Male rats were divided into four groups(SHR,SHR+ALA,SHR+L-NAME,SHR+ALA+L-NAME).The respective group of rats was administered with ALA(100 mg/kg/day)from age 4 weeks to 28 weeks and L-NAME(25 mg/kg/day)from age 16 weeks to 28 weeks.SBP was measured every two weeks and twenty four hour urine was collected at 4 weeks,16 weeks and 28 weeks for estimation of protein,creatinine and N-acetyl-e end of 28 weeks,rats were sacrificed and blood and kidneys colα-Dglucosaminidase.At thlected for assessment of blood creatinine,kidney thiobarbituric acid reactive substances,protein carbonyls,superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase,glutathione S-transferase,glutathione disulfide,glutathione,total antioxidant status and nitric oxide as well as histopathological examination.Results:ALA supplementation significantly reduced SBP of SHR and SHR+L-NAME rats when compared to their respective non-supplemented groups.Renal oxidant status markers including thiobarbituric acid reactive substances and protein carbonyls were significantly reduced on SHR and SHR+L-NAME rats supplemented with ALA at 28 weeks as well as ALA supplementation significantly increased renal antioxidants including superoxide dismutase,catalase,glutathione peroxidase,glutathione S-transferase,glutathione and glutathione/glutathione disulfide ratio at 28 weeks.No significant change in nitric oxide levels was observed between the ALA supplemented and non-supplemented groups.Renal dysfunction was ameliorated on ALA supplementation as evidenced by significant reduction in urine protein levels,N-acetyl-α-D-glucosaminidase activity and significant increase of creatinine clearance in SHR and SHR+L-NAME at 28 weeks.Renal histopathological examination showed that ALA supplementation prevented vascular damage in SHR and ameliorated glomerular damage in SHR+L-NAME at 28 weeks.Conclusions:ALA has hypotensive and renoprotective effects on both SHR and SHR+LNAME,which could be due to its ability to ameliorate oxidative stress in the kidneys.
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:Relevance of cardiac autonomic neuropathy has not been fully recognized and there is no standardized treatment protocol.Aim:To evaluate the effects of alpha-lipoic acid on the beat-to-beat vectorcardiographic parameters,namely spatial QRS-T angle,QT dispersion(QTd)and corrected QT interval(QTc)in type 2 diabetes mellitus persons with cardiac autonomic neuropathy.Research designs and methods:Our study involved 33 persons with definite stage of cardiac autonomic neuropathy and diabetes mellitus type 2,which were assigned to each of two groups:one took standard antihyperglycaemic treatment(n=15,control group)and the other(n=18)in addition to standard therapy-600 mg of alpha-lipoic acid daily for three months.The analysis of vectorcardiographic parameters was performed.Results:It was found out that alpha-lipoic acid contributed to decrease of the vectorcardiographic parameters,namely QRS-T angle,QTd and QTc.Conclusions:The positive influences of alpha-lipoic acid suggest the usefulness of its prescription to type 2 diabetes mellitus persons with definite stage of cardiac autonomic neuropathy.The efficacy of alpha-lipoic acid is the result of its direct effect on the parameters of vectorcardiography.
文摘Background Cardiac failure is a leading cause of the mortality of diabetic patients. In part this is due to a specific cardiomyopathy, referred to as diabetic cardiomyopathy. Oxidative stress is widely considered to be one of the major factors underlying the pathogenesis of the disease. This study aimed to test whether the antioxidant α-lipoic acid （α-LA） could attenuate mitochondrion-dependent myocardial apoptosis through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy. Methods A rat model of diabetes was induced by a single tail intravenous injection of streptozotocin （STZ） 45 mg/kg. Experimental animals were randomly assigned to 3 groups： normal control （NC）, diabetes （DM） and DM treated with α-LA （α-LA）. The latter group was administered with a-LA （100 mg/kg ip per day）, the remainder received the same volume vehicle. At weeks 4, 8, and 12 after the onset of diabetes, cardiac apoptosis was examined by TUNEL assay. Cardiomyopathy was evaluated by assessment of cardiac structure and function. Oxidative damage was evaluated by the content of malondialdehyde （MDA）, reduced glutathione （GSH） and the activity of manganese superoxide diamutase （Mn-SOD） in the myocardial mitochondria. Expression of caspase-9 and caspase-3 proteins was determined by immunohistochemistry and mitochondrial cytochrome c release was detected by Western blotting Results At 4, 8, and 12 weeks after the onset of diabetes, significant reductions in TUNEL-positive cells, caspase-9,-3 expression, and mitochondrial cytochrome c release were observed in the α-LA group compared to the DM group. In the DM group, the content of MDA in the myocardial mitochondria was significantly increased, and there was a decrease in both the mitochondrial GSH content and the activities of Mn-SOD. They were significantly improved by α-LA treatment. HE staining displayed structural abnormalities in diabetic hearts, while α-LA reversed this structural derangement. The index of cardiac function （±dp/dtmax） in the diabetes group was aggravated progressively from 4 weeks to 12 weeks, but α-LA delayed deterioration of cardiac function （P 〈0.05）. Conclusions Our findings indicate that the antioxidant α-LA can effectively attenuate mitochondria-dependent cardiac apoptosis and exert a protective role against the development of diabetic cardiomyopathy. The ability of α-LA to suppress mitochondrial oxidative damage is concomitant with an enhancement of Mn-SOD activity and an increase in the GSH content of myocardial mitochondria.
文摘目的用Meta分析对临床使用α-硫辛酸联合甲钴胺治疗糖尿病周围神经病变的方案进行分析,评价其治疗效果。方法利用中国学术期刊全文数据库(CNKI)、万方全文数据库,检索到2008～2012年国内发表的α-硫辛酸联合甲钴胺治疗糖尿病周围神经病变临床试验的相关文献,应用Meta分析软件包Rev Man 5.0对各研究结果进行数据合并,并进行发表偏倚分析。结果共纳入文献12篇,859例糖尿病周围神经病变患者,各研究结果间存在同质性(P=0.85>0.05),α-硫辛酸与甲钴胺治疗联合治疗组总体有效率明显高于对照组[P<0.000 01,(OR=5.30,95%CI:3.59～7.82)]。结论与单独使用甲钴胺相比,采用α-硫辛酸联合甲钴胺的方法治疗糖尿病周围神经病变更加有效。
