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Abstract Objectives Olfactory loss is a recognized long-term dysfunction after Coronavirus Disease 2019 (COVID-19) infection. This investigation aimed to assess the effect of alpha-lipoic acid as an adjuvant treatment of olfactory training on the improvement of smell loss in post-COVID-19 patients. Methods This randomized controlled trial included 128 adult outpatients who had persistent smell loss for more than 3-months after COVID-19 infection. The participants were randomly allocated into two groups: the intervention treatment group, which received alpha-lipoic acid associated to olfactory training, and comparison treatment group, which received placebo pills associated to olfactory training. The participants were followed-up for 12-weeks. Olfactory dysfunction was assessed in terms of Visual Analog Scale (VAS), and the Connecticut Chemosensory Clinical Research Center (CCCRC) test for the Brazilian population. Results A total of 100 participants completed the follow-up period and were analyzed in this study. Both groups have improved CCCRC score (p= 0.000), olfactory threshold (p= 0.000), identification score (p= 0.000) and VAS score (p= 0.000) after 12-weeks follow-up. No significant differences were determined between the intervention and comparison treatment groups in CCCRC score (p= 0.63), olfactory threshold (p= 0.50), identification score (p= 0.96) and VAS score (p= 0.97). In all these criteria, comparison treatment group went slightly worse. At the endpoint of the study, the frequency of anosmia reduced to 2% in the intervention treatment group and to 7.8% in the comparison treatment group. Also, 16.8% of the intervention group' subjects, and 15.7% of comparison treatment group's patients reached normosmia. Conclusions Overall, there was a strongly significant difference in olfactory function between baseline and endpoint for both groups. However, based on the lack of significant difference between the intervention treatment and the comparison treatment groups in terms of olfactory changes, our study appoints that the alpha-lipoic acid is not better than olfactory training alone to treat olfactory loss after COVID-19. Level of evidence Level 2.
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Objective:To explore the protective effect of α-lipoic acid (LA) on radiation damage of mice cochlear ribbon synapses.Methods:Mice were divided into five groups: control group, radiation 3 d group, radiation 3 d+ LA group, radiation 14 d group and radiation 14 d+ LA group. The radiation groups were irradiated with 16 Gy, the radiation+ LA groups were given LA once a day after radiation, the control group was given the same amount of normal saline. The auditory brainstem response (ABR) of mice were measured before irradiation and sacrifice. The number of ribbon synapses were observed with immunofluorescently labeled protein ctBP2. Western blot assay was performed to obtain the semi-quantitative expression levels of otoferlin and AP-2 protein.Results:Compared with the control group, the ABR threshold of radiation groups were significantly higher ( P<0.05) with the highest value at 14 d after irradiation ( P<0.05), and the ABR threshold of the radiation+ LA groups were significantly lower ( P<0.05). The ABR threshold shifts of 12 kHz, 24 kHz at 3 d and 14 d groups had no significant difference with 8 kHz threshold shift ( P>0.05). The 32 kHz threshold shift was significantly higher than 8 kHz threshold shift ( t=-2.38, -5.48, P<0.05). The number of ribbon synapses in the radiation groups was significantly lower than that of control group ( P<0.05), with the lowest value in the radiation 14 d group. LA treatment increased the ABR value significantly ( P<0.05). AP-2 and otoferlin protein levels were significantly reduced after irradiation, especially in the radiation 14 d groups, and they were increased by the LA treatment. Conclusions:LA has protective effect on the ribbon synapses of cochlear hair cells.
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Objective:To observe the clinical efficacy of Shenxie Zhitong capsule in the treatment of diabetic peripheral neuropathy（DPN） of stagnant blockade of collaterals， and evaluate its effectiveness and safety. Method:The 104 patients were randomly divided into the Shenxie Zhitong capsule treatment group （the treatment group， 53 patients） and the alpha lipoic acid group （control group， 51 patients）， and two groups were compared by random and contrast test. The changes of the Toronto clinical scoring system （TCSS）， utah early neuropathy scores （UENS）， traditional Chinese medicine（TCM）syndrome scores， visual analysis scale （VAS）， ankle brachial index （ABI）， vibrating perception threshold （VPT） before and after treatment were compared between two groups， and the endpoint events， such as foot ulcers， percutaneous coronary intervention （PCI）， death and composite endpoint events， related indicators of glucose and lipid metabolism and safety indicators were recorded among patients. Result:Compared with the data before treatment， the scores of TCSS， UENS， and TCM syndromes in two groups were significantly reduced （<italic>P</italic><0.01） after treatment， and VAS and glycosylated haemoglobin A1c （HbA1c） were significantly reduced （<italic>P</italic><0.05）， during follow-up visit， the levels of right ABI，total cholesterol （TC）， and low-density lipoprotein （LDL） in two groups were significantly reduced （<italic>P</italic><0.05）， and high-density lipoprotein （HDL） level was significantly increased （<italic>P</italic><0.05）. control group in control group， the 2-hour postprandial plasma glucose （2 h PG） and HbA1c levels were significantly increased （<italic>P</italic><0.05）. Compared with control group， the VAS of the treatment group after treatment was significantly reduced （<italic>P</italic><0.05）. After treatment and during follow-up visit， compared with control group， the 2 h PG levels of the right toe in the treatment group were significantly reduced （<italic>P</italic><0.05）. There was no statistically significant difference in endpoint events and safety indicators between two groups， but the incidence trend of composite endpoint events in the treatment group was lower than that in control group. Conclusion:Shenxie Zhitong capsule has definite clinical curative effect in treating diabetic peripheral neuropathy， which is more safe and effective than alpha lipoic acid in improving pain symptoms.
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Background: Diabetic peripheral sensorimotor polyneuropathy is the most common complication seen in patients with diabetes mellitus (DM). Oxidant system plays a crucial role in its physiopathology. We investigated the changes in the serum levels of total antioxidant status (TAS), total oxidant status (TOS), paraoxonase-1 (PON1) and oxidative stress index (OSI) to evaluate the antioxidant efficacy of alpha lipoic acid (ALA) and/or gabapentin in patients with diabetic polyneuropathy (DPN).Methods: Sixty-three type 2 DM patients with diabetic polyneuropathy (DPN) were enrolled in the study. Patients with DPN were divided into four groups in terms of their treatment: Group 1 consisted of treatment-naive patients; patients treated with ALA, gabapentin or combination of ALA and gabapentin comprised groups 2, 3, and 4, respectively. The patients received the medications for at least six weeks. Serum levels of TAS, TOS, PON1 and OSI were analyzed.Results: No significant difference was observed between the groups according to the oxidative stress parameters studied.Conclusions: The use of ALA and/or gabapentin in patients with DPN did not significantly affect the oxidative stress parameters, including TAS, TOS, PON1, and OSI.
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@#Introduction:Carpal tunnel syndrome is one of the most common peripheral neuropathies. Only a few studies evaluate the efficacy of “nutraceuticals” on peripheral nerves and neuropathic pain. The aim of the present investigation is to evaluate the role of Alfa-Lipoic Acid-R (ALA-R) on clinical and functional outcomes in patients affected by mild to moderate carpal tunnel syndrome. Material and Methods: The present investigation is a prospective randomised controlled open label study, performed at our Hand Surgery Department (Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome) from October 2018 to March 2019. The enrolled patients were divided in two groups: Group A (ALA-R 600mg once day for 60 days) and Group B (control Group, no drug administration). Results: 134 patients (74 F, 60 M) met the inclusion and exclusion criteria. In Group A, there was a statistically significant pain reduction compared to the control Group. Using the Boston Carpal Tunnel Questionnaire, there were no significant improvements in the other symptoms and function. Conclusion: ALA-R full dose administration for two months leads to positive short term results in terms of symptoms and function improvement, even if the surgical carpal tunnel release remains the treatment of choice.
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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-β-D-glucosaminidase. At the end of 28 weeks, rats were sacrificed and blood and kidneys collected 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-β-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+L-NAME, which could be due to its ability to ameliorate oxidative stress in the kidneys.
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Objective To investigate the clinical efficacy of mecobalamin Zusanli acupoint injection combined with α-lipoic acid intravenous infusion in the treatment of patients with diabetic peripheral neuropathy.Methods From February 2016 to August 2017,80 patients with diabetic peripheral neuropathy in Zhoushan Hospital were divided into control group and treatment group according to different treatment methods,with 40 cases in each group.The two groups were given diet,exercise and medication.At the same time,the control group was given mecobalamin Zusanli acupoint injection,the treatment group was given α-lipoic acid intravenous infusion on the basis of the control group.After 2 weeks of treatment,the clinical curative effect was evaluated.The scores of MDNS before and after treatment were evaluated.The motor nerve conduction velocity (MNCV),sensory nerve conduction velocity (SNCV),and the shortest F wave latent period velocity of the tibial nerve were compared before and after treatment in the two groups.The adverse reactions during treatment in the two groups were recorded.Results The total effective rate of the treatment group was 87.5％,which was significantly higher than 52.5％ of the control group(x2 =12.621,P =0.001).The MDNS score of the treatment group after 2 weeks of treatment was (1.82 ±0.74)points,which was significantly lower than (2.45 ± 0.89) points of the control group (t =3.442,P =0.000).After treatment,the MNCV of the common peroneal nerve of the treatment group was (48.12 ±4.98) m/s,which was significantly higher than (42.68 ± 4.59)m/s of the control group (t =5.080,P =0.000).The median nerve MNCV of the treatment group was (53.31 ± 4.41)m/s,which was significantly higher than (49.85 ± 3.87)m/s of the control group (t =3.729,P =0.000).After treatment,the SNCV of the common peroneal nerve in the treatment group was (42.73 ± 4.28) m/s,which was significantly higher than (39.57 ± 3.65) m/s in the control group (t =3.552,P =0.000).The median nerve SNCV of the treatment group was (46.98 ± 3.47) m/s,which had no statistically significant difference compared with that of the control group [(45.79 ± 3.56) m/s] (t =1.513,P =0.134).The shortest F wave latent period velocity of the tibial nerve in the treatment group was (45.82 ±4.12) m/s,which was significantly higher than (42.68 ± 3.25) m/s in the control group(t =3.784,P =0.000).The two groups had no obvious adverse reactions during treatment.Conclusion Mecobalamin Zusanli acupoint injection combined with α-lipoic acid intravenous infusion in the treatment of patients with diabetic peripheral neuropathy is effective and safe,and it is worthy of promoting.
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Aim: To investigate the effects of alpha lipoic acid (ALA) on Notch2, TLR4, NLRP3 and inflammatory factor expression in renal tissues of diabetes mellitus(DM) rats, and to explore its possible mechanism of anti-inflammatory and anti-fibrosis by Alpha lipoic acid. Methods: The diabetic rat model was established by streptozotocin. The rats were divided into two groups; the DM group and ALA group. Meanwhile, and another eight rats were used as normal control (NC group). After eight weeks, the rats were sacrificed to detect the relevant biochemical parameters and oxidative stress indexes. In addition, immunohistochemical staining was employed to detect the protein expression localization sites of Notch2, TLR4 and NLRP3. Western blot analysis was used to detect the expression of Notch2, TLR4, NLRP3 and collagen FV proteins in renal tissues. ELISA was utilized to detect the inflammatory factor expression of IL-6 and TNF-α. Results: Compared with NC group, the levels of blood glucose, 24h urine protein, total cholesterol and triglyceride all increased in DM group, and the activity of T-AOC was reduced whereas MDA content was up-regulated in DM group, all items but blood glucose were significantly reduced in ALA group, and the activity of T-AOC remarkably increased, while MDA content was reduced in ALA group. Compared with NC group, the protein levels of Notch2, TLR4, NLRP3 and collagen IV in kidneys were raised, and the inflammatory factor expression of IL-6 and TNF-α significantly increased in DM group. Conclusions: ALA may down-regulate the inflammatory signal of TLR4 and NLRP3 in kidney of diabetic rats, and reduce the expression of inflammatory factor and the accumulation of extracellular matrix via inhibiting the expression of Notch2 at protein level.
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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 N
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Objective To investigate whether alpha-lipoic acid (ALA) possesses neuroprotective effects against high glucose-induced damage in vitro.Methods The cultured human lens epithelial cells (HLEC-B3 cells) were divided into normal control group,high glucose group and ALA group.Normal control group left untreated,ALA group was pretreated with different concentrations of ALA (25 μmol · L-1,50 μmol · L-1,100 μmol · L-1) for 1h,and then ALA group and high glucose group were cultured under high glucose conditions for 48h.After above treatment,the activity of lens epithelial cells in each group was detected immediately by MTT,and the changes in intracellular reactive oxygen species (ROS) were detected by flow cytometry.In addition,the expression of manganese superoxide dismutase (MnSOD) was detected by Western blot and RT-PCR in all groups.Results The activity of HLEC-B3 cells in high glucose group was 53.60％ ±4.10％,which was significantly lower than that in normal control group (P ＜ 0.01).The cell viability in 25 μmol · L-1,50 μmol · L-1,100 μmol · L-1 ALA group was 65.30％ ± 3.70％,72.70％ ± 4.90％ and 83.40％ ± 3.60％,respectively,all which were higher than those in the high glucose group (all P ＜ 0.05).Flow cytometry showed that intracellular ROS level in the high glucose group was significantly higher than that in the normal control group (P ＜ 0.01),but ROS levels were decreased to 14.70％ ±0.70％,8.70％ ±0.87％,5.20％ ±0.53％ after25 μmol· L-1,50 μmol· L-1,100 μmol · L-1 ALA treatment,respectively,with significant difference (all P ＜ 0.01).RT-PCR and Western blot results indicated that the relative expression of MnSOD mRNA and protein in the high glucose group was significantly lower than that in the normal control group (all P ＜ 0.01).Compared with the high glucose group,MnSOD mRNA and protein relative expression levels were significantly increased to 0.63 ± 0.06,0.71 ± 0.06,0.84 ± 0.04,and 0.25 ± 0.03,0.31 ± 0.02,0.45 ± 0.04,respectively (all P ＜ 0.05).In addition,the protective effects of ALA (25-100 μmol · L-1) on HLEC-B3 cells induced by high glucose was in a dose-dependent manner.Conclusion ALA has a protective effect on human lens epithelial cell line HLEC-B3 cultured in high glucose condition,and this protective effect may be achieved by increasing the expression level of intracellular MnSOD.
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BACKGROUND: Performing high intensity or exhaustive exercise can lead to muscle damage such as injuries, chronic fatigue and overtraining, partly due to the high synthesis of reactive oxygen species. The α-lipoic acid (ALA) and its reduced form, dihydrolipoic acid, act as potent antioxidant and eliminate free radicals. Although this response depends on the type of exercise and supplementation, animal and human studies have shown the benefits of antioxidant supplementation on the recovery of damages caused by exhaustive exercise, either by restoring antioxidant levels or by decreasing the damage. OBJECTIVE: We evaluated the effect of ALA supplementation on muscular biomarkers of oxidative stress following exhaustive exercise of trained mice. METHODS: Sixty mice were trained to swim for 6 weeks. On the last week, half of the animals were supplemented daily with 100 mg/kg of oral gavage of ALA in soy oil as a vehicle. The other half received just the vehicle. On the last day 20 animals from each group were submitted to an exhaustion protocol with 10% overweight attached to tail. Animals were euthanized on 3 moments: basal, just after the exhaustive protocol (0 h) and, 4 h after the exhaustive protocol. The gastrocnemius muscle was promptly excised and homogenized. The homogenates were used to estimate oxidative stress biomarkers. RESULTS: There was a simultaneous decrease of non-protein thiols and vitamin E after 4 h of exhaustive exercise in the ALA group (p<0.05) compared to the control group, suggesting the consumption of these compounds in the process of lipid peroxidation. Interestingly, there was an increase of nitrate and nitrite in ALA group (p<0.05) and a decrease in the control (p<0.05) compared to basal moment, possibly by activation of endothelial nitric oxide synthase. The total antioxidant capacity remained unchanged in the ALA group. CONCLUSION: The supplementation with ALA resulted in a protection against oxidative stress caused by exhaustive exercise.
CONTEXTO: A realização de exercício de alta intensidade ou exaustivo pode levar a danos musculares, como lesões, fadiga crônica e overtraining, em parte devido à alta síntese de espécies reativas de oxigênio. O ácido α-lipóico e sua forma reduzida, o ácido dihidrolipóico, atuam como potentes antioxidantes e eliminam os radicais livres. Apesar de depender do tipo de exercício e suplementação, estudos com animais e humanos mostram benefícios da suplementação com antioxidante na recuperação de danos causados pelo exercício exaustivo, seja restaurando os níveis de antioxidantes ou diminuindo os danos. OBJETIVO: Avaliar o efeito da suplementação com ácido α-lipóico sobre biomarcadores musculares de estresse oxidativo após o exercício exaustivo de camundongos treinados. METODOLOGIA: Os camundongos (n = 60) foram treinados em natação por 6 semanas. Na última semana, metade dos animais foram suplementados diariamente com gavagem oral de 100 mg / kg de ácido α-lipóico em óleo de soja como veículo. A outra metade recebeu apenas o veículo. No último dia 20 animais de cada grupo foram submetidos ao protocolo de exaustão com 10% de sobrepeso atado à cauda. Os animais foram eutanasiados em 3 momentos: basal, logo após o protocolo de exaustão (0 h) e 4 h após o protocolo de exaustão. O músculo gastrocnêmio foi imediatamente coletado e homogeneizado. Os homogeneizados foram usados para acessar os biomarcadores de estresse oxidativo. RESULTADOS: Houve diminuição simultânea de tióis não protéicos e vitamina E após 4 h de exercício exaustivo no grupo ácido α-lipóico (p <0,05) em relação ao grupo controle, sugerindo o consumo destes compostos no processo de peroxidação lipídica. Interessantemente, houve aumento de nitrato e nitrito no grupo ácido α-lipóico (p <0,05) e diminuição no controle (p <0,05) em relação ao momento basal, possivelmente pela ativação da óxido nítrico sintase endotelial. A capacidade antioxidante total permaneceu inalterada no grupo ácido α-lipóico. CONCLUSÃO: A suplementação com ácido α-lipóico resultou em proteção contra o estresse oxidativo causado pelo exercício exaustivo.
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Animals , Mice , Thioctic Acid/analysis , Oxidative Stress/drug effects , Physical Exertion/physiology , Antioxidants/therapeutic use , Biomarkers/analysisABSTRACT
Objective@# To explore the effects of lipoic acid in the treatment of burning mouth syndrome. @*Methods @# From May 2015 to May 2016, patients with burning mouth syndrome were selected and divided into experimental group (n=14) and control group (n=15). Patients were treated with lipoic acid in the experiment group while oryzanol, vitamin B2 and vitamin were given in the control group. The pain degrees in two groups were compared before and after treatment, and the adverse drug reaction were monitored during the process. @*Results@# Before and after 1 week treatment, there was no statistical difference between VAS scores in two groups (P > 0.05). However, there were significant differences after 2 or 3 weeks (P < 0.05). Improvement of VAS score was found in both groups after treatment (P < 0.05). No adverse drug reaction was found during the treatment. @*Conclusion @#Lipoic acid can relieve the pain of patients with burning mouth syndrome.
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Insulin autoimmune syndrome (IAS) is characterized by spontaneous hypoglycemia, extremely high serum insulin levels, and high titers of autoantibodies against endogenous insulin, in the absence of exogenous insulin injection. IAS often occurs following exposure to sulfhydryl-containing drugs, including alpha-lipoic acid (ALA). A 30-year-old woman without diabetes visited our outpatient clinic with recurrent hypoglycemia. She had been taken ALA for weight reduction since 3 weeks ago. Further hypoglycemia work up revealed very high insulin levels, C-Peptide levels and positive insulin antibodies. And conventional imaging examinations were negative for insulinoma or other pancreatic tumors. Finally, the diagnosis of Insulin autoimmune syndrome (IAS) was made. Following the cessation of ALA, hypoglycemia improved, with no medication, and the patient experienced no further hypoglycemic attacks over the next month. The use of ALA as a nutritional supplement is increasing. We report a case of IAS associated with ALA in a non-diabetic patient.
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Adult , Female , Humans , Ambulatory Care Facilities , Autoantibodies , C-Peptide , Diagnosis , Hypoglycemia , Insulin Antibodies , Insulin , Insulinoma , Thioctic Acid , Weight LossABSTRACT
Insulin autoimmune syndrome (IAS) is characterized by spontaneous hypoglycemia, extremely high serum insulin levels, and high titers of autoantibodies against endogenous insulin, in the absence of exogenous insulin injection. IAS often occurs following exposure to sulfhydryl-containing drugs, including alpha-lipoic acid (ALA). A 30-year-old woman without diabetes visited our outpatient clinic with recurrent hypoglycemia. She had been taken ALA for weight reduction since 3 weeks ago. Further hypoglycemia work up revealed very high insulin levels, C-Peptide levels and positive insulin antibodies. And conventional imaging examinations were negative for insulinoma or other pancreatic tumors. Finally, the diagnosis of Insulin autoimmune syndrome (IAS) was made. Following the cessation of ALA, hypoglycemia improved, with no medication, and the patient experienced no further hypoglycemic attacks over the next month. The use of ALA as a nutritional supplement is increasing. We report a case of IAS associated with ALA in a non-diabetic patient.
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Adult , Female , Humans , Ambulatory Care Facilities , Autoantibodies , C-Peptide , Diagnosis , Hypoglycemia , Insulin Antibodies , Insulin , Insulinoma , Thioctic Acid , Weight LossABSTRACT
The epithelial cytokine response, associated with reactive oxygen species (ROS), is important in Helicobacter pylori (H. pylori)-induced inflammation. H. pylori induces the production of ROS, which may be involved in the activation of mitogen-activated protein kinases (MAPK), janus kinase/signal transducers and activators of transcription (Jak/Stat), and oxidant-sensitive transcription factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), and thus, expression of interleukin-8 (IL-8) in gastric epithelial cells. alpha-lipoic acid, a naturally occurring thiol compound, is a potential antioxidant. It shows beneficial effects in treatment of oxidant-associated diseases including diabetes. The present study is purposed to investigate whether alpha-lipoic acid inhibits expression of inflammatory cytokine IL-8 by suppressing activation of MAPK, Jak/Stat, and NF-kappaB in H. pylori-infected gastric epithelial cells. Gastric epithelial AGS cells were pretreated with or without alpha-lipoic acid for 2 h and infected with H. pylori in a Korean isolate (HP99) at a ratio of 300:1. IL-8 mRNA expression was analyzed by RT-PCR analysis. IL-8 levels in the medium were determined by enzyme-linked immunosorbent assay. NF-kappaB-DNA binding activity was determined by electrophoretic mobility shift assay. Phospho-specific and total forms of MAPK and Jak/Stat were assessed by Western blot analysis. ROS levels were determined using dichlorofluorescein fluorescence. As a result, H. pylori induced increases in ROS levels, mRNA, and protein levels of IL-8, as well as the activation of MAPK [extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal kinase 1/2 (JNK1/2), p38], Jak/Stat (Jak1/2, Stat3), and NF-kappaB in AGS cells, which was inhibited by alpha-lipoic acid. In conclusion, alpha-lipoic acid may be beneficial for prevention and/or treatment of H. pylori infection-associated gastric inflammation.
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Humans , Enzyme-Linked Immunosorbent Assay , Epithelial Cells/metabolism , Gastric Mucosa/drug effects , Gene Expression Regulation, Bacterial , Helicobacter Infections/immunology , Helicobacter pylori/drug effects , Interleukin-8/genetics , JNK Mitogen-Activated Protein Kinases , Janus Kinase 1 , Mitogen-Activated Protein Kinases/biosynthesis , NF-kappa B/metabolism , RNA, Messenger/isolation & purification , Reactive Oxygen Species/metabolism , STAT3 Transcription Factor , Stomach/metabolism , Thioctic Acid/pharmacologyABSTRACT
Globally liver disorders are major cause of illness death and death. Oxidative stress plays a critical role in the progression of alcoholic and nonalcoholic related diseases. The aim of the present study was to evaluate the efficacy and tolerability of fixed dose combination (FDC) of silymarin, alpha lipoic acid, N-acetyl cysteine and selenium in the management of liver disorders. This was an observational, non-randomized, open label, non-comparative, multi-centric post-marketing surveillance study. The above mentioned FDC was administered to 15 patients diagnosed with alcoholic or viral hepatitis for three months. Evaluation of liver function tests (LFT) were carried out at baseline and at the end of 3rd month of the treatment. Significant changes were observed in the LFT parameters at the end of three months of this study. aspartate aminotransferase (AST): (Mean ± SEM) 369.9 ± 128.0 to 97.00 ± 34.27 U/L, (p < 0.0001); alanine aminotransferase (ALT): 652.93 ± 214.57 to 194.40 ± 82.51 U/L, (p < 0.03); Alkaline phosphatase: 197.47 ± 25.57 to 151.60 ± 17.92 U/L, (p < 0.0059); Gamma glutamyl transferase: 156.67 ± 49.80 to 87.33 ± 22.94 U/L, (p < 0.0490); Total bilirubin: 3.44 ± 0.76 to 1.66 ± 0.57 mg/dL, (p < 0.0192) and bilirubin direct: 2.13 ± 0.58 to 1.00 ± 0.50 mg/dL, (p < 0.0273). Two patients reported mild gastrointestinal adverse events (nausea, bloating). This FDC was therapeutically effective under the circumstances of elevated oxidative stress and produces significant reduction in LFT parameters in alcoholic and viral hepatitis patients.
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Objective To observe the effect of alpha lipoic acid on quality of life in patients with type 2 diabetic peripheral neuropathy.Methods 76 cases diagnosed with type 2 diabetic peripheral neuropathy,in accordance with the random number table,were divided into the control group (37cases)and treatment group (39cases).All the patients received diabetic diet,exercise guidance and blood glucose control.The control group was treated with methy-cobal 500μg muscle injection once a day for 2 weeks.The treatment group was treated besides above treatment with intravenous drip alpha lipoic acid 600mg once a day was added for 2 weeks.Then,the changes of motor nerve conduc-tion velocity,sensory nerve conduction velocity and quality of life (QoL)score (somatic symptoms,cognitive func-tion,health happy feeling,social participation,emotional state,work performance,life satisfaction and total score)of the two groups after treatment were observed.Results After treatment,the motor nerve conduction velocity of the control group were as follows:median nerve (40.7 ±4.5)cm/s,common peroneal nerves (41.3 ±4.9)cm/s,The sensory nerve conduction velocity of the control group were as follows:median nerve (38.6 ±4.3)cm/s,common per-oneal nerves (38.3 ±4.5)cm/s.After treatment,the motor nerve conduction velocity of the treatment group were as follows:Median nerve (45.4 ±5.7)cm/s,common peroneal nerves (44.9 ±6.4)cm/s,The sensory nerve conduction velocity of the treatment group were as follows:Median nerve (45.0 ±2.0)cm/s,common peroneal nerves (43.6 ± 3.2)cm/s.Both the two groups′motor nerve conduction velocity and sensory nerve conduction velocity were significantly increased after treatment (P <0.05).Compared with control group,the motor nerve conduction velocity and sensory nerve conduction velocity in the treatment group were significantly improved after treatment,which had statistically significance,(t =2.63,2.51,2.85,2.79,all P <0.05).After treatment,the somatic symptoms,cognitive function,health happy feeling,job performance,social participation,emotional state,life satisfaction and the total score of control group were (52.4 ±9.6)points,(27.0 ±7.8)points,(35.7 ±10.3)points,(19.6 ±7.3)points,(17.4 ± 3.1)points,(16.5 ±3.9)points,(185.4 ±40.7)points,respectively.After treatment,the somatic symptoms,cogni-tive function,health happy feeling,job performance,social participation,emotional state,life satisfaction and total score of treatment group were (41.9 ±7.4)points,(24.1 ±8.6)points,(28.3 ±9.2)points,(14.5 ±5.5)points, (12.6 ±5.6)points,(11.9 ±4.7)points,(135.0 ±38.7)points,respectively.The quality of life score of the treat-ment group was obviously lower than the control group,which had statistically significance,(t =5.14,2.54,2.96, 2.87,2.69,3.05,6.25,all P <0.05).Conclusion Alpha lipoic acid can improve the nerve conduction function of patients with type 2 diabetes peripheral neuropathy,and improve the quality of life.
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Objective To investigate the effect of alpha-lipoic acid on oxidative stress and cerebral edema after hypoxic-ischemic brain damage (HIBD)in neonatal rats.Methods A total of 108 neonatal 7-day-old Wistar rats were randomly divided into 3 groups:sham-operated group(sham, n=36), HIBD group(HIBD, n=36) and alpha-lipoic acid-treated group (treated group, n=36).Each group was divided into 3 sub-groups (n=12, per sub-group) based on different time points after HIBD (1 d, 3 d, 7 d).HIBD rat models were established by ligating the left common carotid artery, The sham-operated group and the HIBD group were treated with normal sodium injection intraperitoneally; treated group were treated with alpha-lipoic acid 100 mg/kg every 12 hours in 5 days.Animals were sacrificed at different time points.Changes of brain water content were determined by dry-wet weight method.And the levels of SOD,MDA,GSH-PX were measured.Results HIBD group showed an upward trend in brain water content and the level of MDA after HIBD, were higher than that of sham-operated group at each time point (P<0.05).Meanwhile, the levels of SOD and GSH-PX showed the downward trend in HIBD group.The levels of brain water content and the level of MDA in treated group were significantly lower than HIBD group at each time point ( P<0.05 ) .And the levels of SOD and GSH-PX in treated group were significantly higher than HIBD group at 3 d and 7 d.on the contrary , the level of MDA in treated group was significantly lower than HIBD group at 3 d and 7 d.Conclusion Alpha-lipoic acid can amiliorate cerebral edema, so it can prevent HIBD.The neuronal protective mechanism might be reverse oxidative imbalance in the brain of neonatal rats with HIBD.
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Objective To examine whether alpha lipoic acid (LA) regulates high glucose-induced mesangial cell proliferation via mammalian target of rapamycin (mTOR) signaling.Methods The cell proliferation and cycle were determined by methylthiazoletetrazolium(MTT) assay and flow cytometry,respectively.The mRNA expression of AMP-activated protein kinase(AMPK) was detected by realtime PCR.The phosphorylation levels of protein kinase B (Akt),mTOR,eukaryotic translation initiation factor 4E binding protein 1 (4EBP1),and 70S6 kinase (p70S6K) were measured by Western blot.Results 0.25 mmol/L LA promoted high glucose-sitmulated rat mesangial cell proliferation(P＜0.01) and entry of cell cycle into S phase(P＜0.01),along with increased phosphorylation levels of Akt,mTOR,p70S6K,and 4EBP1 (P＜0.05).These effects of 0.25 mmol/L LA disappeared when Akt activity was inhibited.On the contrary,1.0 mmol/L LA inhibited high glucose-induced cell proliferation(P＜0.01) and entry of cell cycle into S phase(P＜0.01),with the decreased phosphorylation levels of mTOR,p70S6K,and 4EBP1 (P＜ 0.05) and the enhanced activity of AMPK(P＜0.01).These effects of 1.0 mmol/L LA were prevented when AMPK activity was inhibited.Conclusions LA dose-dependently regulates mesangial cell proliferation induced by glucose via mTOR signaling pathway.
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Objective To investigate the protective effects of alpha-lipoic (α-LA) on H9c2 cardiomyocytes under-going hypoxia or hypoxia/reoxygenation(H/R) injury and explore its possible mechanisms. Methods H9c2 car-diomyocytes in hypoxia or H/R injury researches were respectively divided into normal control group, hypoxia or H/R group, hypoxia or H/R + α-LA group (LA group), hypoxia or H/R+α-LA + Daidzin group (Daidzin group) and hypoxia or H/R+α-LA +DMSO group ( DMSO group) . The myocardial cell survival was detected by MTT,the activity of LDH and ALDH2 were respectively analyzed by microtitration and ELISA,the MDA level was measured by TBA. Results Compared to the normal control group, the cell survival rates of hypoxia and H/R group were decreased ( P0. 05 ) . Conclusion α-LA can protect H9 c2 cardiomyocytes from hypoxia or H/R injury by means of upregulating activities of ALDH2 and decreasing hypoxia or H/R induced lipid peroxidation.