Efecto del ácido alfa lipoico sobre la peroxidación no enzimática en mitocondrias de corazón y cerebro de rata / Effect of alpha-lipoic acid against non-enzymatic peroxidation of rat heart and brain mitochondria

RESUMEN El ácido alfa lipoico (AAL) ha sido caracterizado como un antioxidante eficiente. Se ha propuesto como un agente terapéutico potencial en el tratamiento o prevención de diferentes alteraciones que pueden estar relacionadas con un desequilibrio del estado celular oxidoreductor. El objetivo de este trabajo fue analizar la sensibilidad a la peroxidación no enzimática (PNE) (ascorbato-Fe++ dependiente) en mitocondrias de corazón y cerebro de ratas incubadas con una solución de AAL. La PNE fue evaluada por el método de quimioluminiscencia (QL). Cuando se compararon las muestras control (sin el agregado del ascorbato-Fe++) con las muestras ascorbato-Fe++ dependientes, se observó un incremento significativo en la emisión lumínica. Simultáneamente, se incubaron las mitocondrias de ambos órganos con diferentes concentraciones de AAL (0,05, 0,15 y 0,25 mg/ml) observándose una protección diferencial. Las mitocondrias de cerebro de rata incubadas con dosis de 0,15 y 0,25 mg/ml de AAL fueron protegidas de los efectos de la PNE, mientras que, en las mitocondrias cardíacas, solo se observó protección con la dosis más alta de AAL (0,25 mg/ml). El análisis de QL indicó que las mitocondrias de cerebro fueron protegidas de manera más eficiente que las mitocondrias de corazón de rata. En este último caso, será necesario probar nuevas dosis de AAL para demostrar los efectos en estas membranas. En conclusión, AAL actuó como un antioxidante protector de las membranas de ambos órganos contra el daño peroxidativo.

ABSTRACT Alphalipoc acid (ALA) has been characterized as an efficient antioxidant. It has been proposed as a potential therapeutic agent in the treatment or prevention of different pathologies that may be related to an imbalance of the oxido reductive cell state. The objective of this work was to analyze the sensitivity to non-enzymatic peroxidation (NEP) (ascorbate-Fe++ dependent) in heart and brain mitochondria of rats incubated with an ALA solution. NEP was evaluated by the chemiluminescence method (CL). When the control samples (without the addition of ascorbate-Fe++) were compared with the ascorbate-Fe++ dependent samples, a significant increase in the light emission. Simultaneously, the mitochondria of both organs were incubated with different concentrations of ALA (0.05, 0,15 and 0,25 mg/ml), observing a differential protection. Rat brain mitochondria incubated with doses of 0.15 and 0,25 mg/ml of ALA were protected from the effects of NEP, while in cardiac mitochondria, protection was only observed with the highest dose of ALA (0,25 mg/ml). The CL analysis indicated that rat brain mitochondria were protected more efficiently than rat heart mitochondria. In the latter case, it will be necessary to test new doses of ALA to demonstrate the effects on these membranes. In conclusion, ALA acted as a protective antioxidant of the membranes of both organs against peroxidative damage.

Influence of alpha lipoic acid supplementation on urinary bladder morphology of diabetic rats / Influencia de la suplementación con ácido alfa lipoico en la morfología de la vejiga urinaria de ratas diabéticas

Diabetes Mellitus (DM) is a condition marked by hyperglycaemia that causes systemic complications, including urinary vesicle dysfunction due to oxidative stress. Further, antioxidants, as well as alpha lipoic acid (ALA), may be a response to this pathological condition. The present study verified the action of ALA as a supplement in ration on glycemia and urinary vesicle structures of rats induced by streptozotocin. The rats were divided into 4 groups: Control (CG), Alpha Lipoic (ALAG), Diabetic control (DCG), and the Diabetic alpha lipoic (DALAG) group. For induction, the diabetic groups were initially induced with streptozotocin (dose 60 mg/kg). Subsequently, group glycemia was evaluated weekly. After 8 weeks, the rats were euthanized and the bladder was collected. The bladders were histologically processed and the slides were stained with Masson's Trichrome for the histomorphometry of epithelial height, connective and muscular tissue and coloration of PicroSirius Red for further analysis of collagen fibers of the bladder. The data of the glycemia demonstrated an inferior median in DALAG compared to DGC (p<0.01). The epithelial height and percentage of the muscle tissue were greater in DALAG compared to the DGC, but not significant. However, GDAL showed improvement in the organization of collagen fibers. In conclusion, bladder the morphology alterations caused by DM were not alleviated by the administration of ALA in 8 weeks of the experiments.

La diabetes mellitus (DM) es una afección marcada por hiperglucemia que causa complicaciones sistémicas, incluida la disfunción de la vejiga urinaria debido al estrés oxidativo. Además, los antioxidantes, así como el ácido alfa lipoico (ALA), pueden ser una respuesta a esta condición patológica. El presente estudio verificó la acción de ALA como suplemento en la ración sobre la glucemia y las estructuras de la vejiga urinaria de ratas inducidas por estreptozotocina. Las ratas se dividieron en 4 grupos: control (CG), alfa lipoico (ALAG), control diabético (DCG) y el grupo diabético alfa lipoico (DALAG). Para la inducción, los grupos diabéticos se aplicó estreptozotocina (dosis 60 mg/kg). Posteriormente, la glucemia grupal se evaluó semanalmente. Después de 8 semanas, las ratas se sacrificaron y se retiró la vejiga urinaria. Las vejigas se procesaron histológicamente y las muestras se tiñeron con tricromo de Masson para la histomorfometría y así evaluar la altura epitelial, el tejido conectivo y muscular. Además se tiñeron cond PicroSirius Red para un análisis posterior de las fibras colágenas de la vejiga urinaria. Los datos de la glucemia demostraron una mediana inferior en DALAG en comparación con DGC (p <0,01). La altura epitelial y el porcentaje de tejido muscular fueron mayores en DALAG en comparación con el DGC, pero no estadísticamente significativos. Sin embargo, GDAL mostró una mejora en la organización de las fibras de colágeno. En conclusión, la morfología de las alteraciones de la vejiga causada por DM no se alivió con la administración de ALA en 8 semanas de estudio.

Fulminant type 1 diabetes mellitus in pregnancy

Fulminant type 1 diabetes mellitus (FT1DM) has received clinical attention for its low incidence and poor prognosis. Currently, few cases of FT1DM are associated with pregnancy in clinical practice, but it poses a great threat to the life of mothers and infants. Here, we present two cases of FT1DM in pregnancy. In Case 1, the patient was a 26-year-old woman who was admitted to the hospital with reduced fetal movement. She was diagnosed with FT1DM and delivered a dead female fetus. Lispro and lantus were administered to control blood glucose, and lipoic acid for antioxidant therapy. In Case 2, the patient was a 28-year-old woman who developed nausea, vomiting, diarrhea, and polydipsia, which later proved to be FT1DM. An abortion was induced and blood glucose levels were controlled using an insulin pump. All physicians should be aware of this disease in order to provide prompt diagnosis and emergency treatment, thus improving maternal prognosis. We suggest that plasma glucose/hemoglobin A1C ratio be adopted as a new clinical parameter in predicting FT1DM.

Antioxidant action of alpha lipoic acid on the testis and epididymis of diabetic rats: morphological, sperm and immunohistochemical evaluation

ABSTRACT Introduction Chronic hyperglycemia is caused by diabetes mellitus-committed genital morphophysiology, and oxidative stress is one of the main factors involved in this process. Alpha lipoic acid (ALA) can prevent metabolic and morphological changes in diabetic individuals. Objectives In present study, we evaluated the effects of regular ALA consumption on the spermatogenesis and histoarchitecture in the male genital system of diabetic rats. Materials and Methods Thirty-two Wistar rats were divided into groups: Control (CG); Diabetic Control (DCG), receiving commercial diet: ALA Group (ALAG) and Diabetic ALA Group (DALAG), fed diets with added ALA (300 mg/Kg bw). The diabetic groups received a single injection of streptozotocin (60 mg/kg). After sixty days of the diet, the animals were euthanized, and semen, testis and epididymis samples were collected. A histomorphometric analysis was performed to determine the epithelial height, tubular and luminal diameter, tubular and luminal area of seminiferous tubules and each epididymal region. Sertoli cells were evidenced using the antivimenti antibody and were quantified. The results were statistically analyzed by the ANOVA test. Results At the end of the experiment, the DALAG glycemia was significantly lower than DCG. The histomorphometric parameters of the seminiferous and epididymal tubules did not show improvement in the DALAG. However, there was an improvement in the DALAG in terms of the concentration, motility and percentage of spermatic pathologies, as well as in the number of Sertoli cells (p<0.001). Conclusions The results demonstrated that supplementation with the ALA antioxidant retards testicular lesions and preserve the process of spermatogenesis in diabetes.

The effect of alpha-lipoic acid on expression of VCAM-1 in type 2 diabetic rat / 대한해부학회지

Biosynthesis of α-lipoic acid in Gluconobacter oxydans increases the production of vitamin C by one-step fermentation / 生物工程学报

In a one-step fermentation system of vitamin C production with Gluconobacter oxydans and Ketogulonicigenium vulgare, a functional module of α-lipoic acid biosynthesis was constructed in G. oxydans. The engineered G. oxydans was co-cultured with K. vulgare to enhance the growth and 2-keto-L-gulonic acid (2-KGA) production of K. vulgare. This one-step fermentation system alleviated the growth inhibition during the mono-culture of K. vulgare and strengthened the interaction between the two bacteria. Moreover, the yield of vitamin C precursor (2-KGA) increased to 73.34 g/L (the control group was 59.09 g/L), and the conversion of D-sorbitol to 2-KGA increased to 86.0%. This study provides a new idea for further optimizing the one-step fermentation system of vitamin C production.

Lipoic acid protects spermatogenesis in male rats with ornidazole-induced oligoasthenozoospermia / 中华男科学杂志

<p><b>Objective</b>To study the protective effect of lipoic acid (LA) on the spermatogenic function of the male rats with oligoasthenozoospermia induced by ornidazole (ORN).</p><p><b>METHODS</b>Seventy male SD rats were equally randomized into groups A (solvent control: 1 ml 0.5% CMC-Na + 1 ml olive oil), B (low-dose ORN model: 400 mg/kg ORN suspension + 1 ml olive oil), C (low-dose ORN + low-dose LA treatment: 400 mg/kg ORN + 50 mg/kg LA), D (low-dose ORN + high-dose LA treatment: 400 mg/kg ORN + 100 mg/kg LA), E (high-dose ORN model: 800 mg/kg ORN suspension + 1 ml olive oil), F (high-dose ORN + low-dose LA treatment: 800 mg/kg ORN + 50 mg/kg LA), and G (high-dose ORN + high-dose LA treatment: 800 mg/kg ORN + 100 mg/kg LA), and treated respectively for 20 successive days. Then all the rats were sacrificed and the weights of the body, testis, epididymis and seminal vesicle obtained, followed by calculation of the organ index, determination of epididymal sperm concentration and motility, and observation of the histomorphological changes in the testis and epididymis by HE staining.</p><p><b>RESULTS</b>Compared with group A, group E showed significantly decreased body weight (［117.67 ± 11.53］ vs ［88.11 ± 12.65］ g, P < 0.01) and indexes of the testis (［1.06 ± 0.12］ vs ［0.65 ± 0.13］ %, P < 0.01) and epididymis (［0.21 ± 0.03］ vs ［0.17 ± 0.01］ %, P < 0.01). In comparison with group E, group F exhibited remarkable increases in the epididymal index (［0.17 ± 0.01］ vs ［0.20 ± 0.02］ %, P < 0.01), and so did group G in the body weight (［88.11 ± 12.65］ vs ［102.70 ± 16.10］ g, P < 0.05) and the indexes of the testis (［0.65 ± 0.13］ vs ［0.95 ± 0.06］ %, P < 0.01) and epididymis (［0.17 ± 0.01］ vs ［0.19 ± 0.02］ %, P < 0.05), but no obvious difference was observed in the index of seminal vesicle among different groups. Compared with group A, group B manifested significant decreases in sperm motility (［74.12 ± 8.73］ vs ［40.25 ± 6.08］ %, P < 0.01), and so did group E in sperm count (［38.59 ± 6.40］ vs ［18.67 ± 4.59］ ×105/100 mg, P < 0.01) and sperm motility (［74.12 ± 8.73］ vs ［27.58 ± 8.43］ %, P < 0.01). Sperm motility was significantly lower in group B than in C and D (［40.25 ± 6.08］ vs ［58.13 ± 7.62］ and ［76.04 ± 8.44］%, P < 0.01), and so were sperm count and motility in group E than in F and G (［18.67 ± 4.59］ vs ［25.63 ± 9.66］ and ［29.92 ± 4.15］ ×105/100 mg, P < 0.05 and P < 0.01; ［27.58 ± 8.43］ vs ［36.56 ± 11.08］ and ［45.05 ± 9.59］ %, P < 0.05 and P < 0.01). There were no obvious changes in the histomorphology of the testis and epididymis in groups A, B, C and D. Compared with group A, group E showed necrotic and exfoliated spermatogenic cells with unclear layers and disorderly arrangement in the seminiferous tubules and remarkably reduced sperm count with lots of noncellular components in the epididymal cavity, while groups F and G exhibited increased sperm count in the seminiferous tubules and epididymis lumen, also with exfoliation, unclear layers and disorderly arrangement of spermatogenic cells, but significantly better than in group E.</p><p><b>CONCLUSIONS</b>LA can reduce ORN-induced damage to the spermatogenetic function of rats, improve sperm quality, and protect the reproductive system.</p>

Effects of the supplementation with alpha-lipoic acid on muscular antioxidant biomarkers of trained mice / Efeitos da suplementação com ácido alfa-lipóico sobre biomarcadores antioxidantes musculares de camundongos treinados

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.

Insulin autoimmune syndrome associated with alpha-lipoic acid in a young woman with no concomitant disease / 영남의대학술지

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.

Efficacy of alpha-lipoic acid combined with tamoxifen citrate in the treatment of oligoasthenospermia / 中华男科学杂志

Objective@#To investigate the effect of alpha-lipoic acid (α-LA) combined with tamoxifen citrate (TC) in the treatment of oligoasthenospermia.@*METHODS@#From June to November 2016, we treated 60 patients with oligoasthenospermia in our Department of Andrology, 30 (the trial group) with oral α-LA (0.6 g, qd) + TC (20 mg, qd) and the other 30 (the control group) with oral L-carnitine (1g, bid) + TC (20 mg, qd). Before and after 3 months of medication, we examined the semen parameters of the patients and the levels of their seminal oxidative stress biomarkers, including methylenedioxyamphetamine (MDA) and total antioxidant capacity (TAC) in the seminal plasma. We also compared the pregnancy rate and adverse reactions between the two groups.@*RESULTS@#Totally, 57 of the patients completed the treatment, 28 in the trial group and 29 in the control. Compared with the baseline, the patients of the trial group showed significant improvement after 3 months of medication in the semen volume (［2.50 ± 0.71］ vs ［3.37 ± 0.70］ ml, P 0.05) except in TAC, which was markedly more improved in the former than in the latter (P 0.05). After 3 months of treatment, 3 pregnancies were achieved in the trial group and 1 in the control (10.7% vs 3.45%, P >0.05). No obvious adverse events occurred during the treatment.@*CONCLUSIONS@#Alpha-lipoic acid combined with tamoxifen citrate can evidently improve semen parameters in oligoasthenospermia patients by relieving oxidative stress injury.

Advances in the studies of lipoic acid in male infertility / 中华男科学杂志

Lipoic acid (LA) is widely present in the body as a disulfide compound with an extensive biological activity and a strong antioxidant capacity. LA plays an antioxidant role by removing oxygen free radicals, chelating metal ions, and regenerating other antioxidants in the body. Recent studies have shown the effects of LA in the prevention or treatment of male reproductive disorders, such as idiopathic oligoasthenozoospermia, diabetes mellitus-induced erectile dysfunction and infertility, serious infection in the reproductive system, and reproductive system injuries caused by chemotherapeutic agents, ionizing radiation, environmental toxins, testicular ischemia reperfusion, excessive exercise, and so on.

Insulin autoimmune syndrome associated with alpha-lipoic acid in a young woman with no concomitant disease / 영남의대학술지

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.

Injections for nutrition and cosmetic purposes: promoted effect vs. objective evidence

The introduction of intravenous nutritional therapy for cosmetic and health purposes in Korea has been controversial. Because it brings ethical problems of off-label prescribing on the basis of low level of medical evidences for claims of fatigue reduction, detoxification, anti-inflammation effect, skin whitening, antioxidant and anti-aging effects. Despite the lack of clinical studies, the verification of the efficacy and safety of intravenous nutritional therapy and the need to provide objective information to patients are prerequisite for the correct intravenous use. In addition, efforts should be made to prevent the abuse for commercial purposes.

Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea

BACKGROUND: Diabetic cardiac autonomic neuropathy (CAN) is one of the important complications of diabetes. It is characterized by reduced heart rate variability (HRV). METHODS: In this randomized, double-blind, placebo-controlled, multicenter trial, 75 patients were randomly assigned to one of two groups. One group (n=41) received α-lipoic acid (ALA) at an oral dose of 600 mg/day for the first 12 weeks and then 1,200 mg/day for the next 12 weeks. The other group (n=34) received placebo treatment for 24 weeks. CAN was assessed by measuring HRVs in people with diabetes. RESULTS: Most of the baseline measures for HRVs were similar between the ALA and placebo groups. Although there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial, we found a positive tendency in some of the HRV parameters of the ALA group. The standard deviations of normal-to-normal RR intervals in the standing position increased by 1.87 ms in the ALA group but decreased by −3.97 ms in the placebo group (P=0.06). The power spectrum of the low frequency (LF) band in the standing position increased by 15.77 ms² in the ALA group, whereas it declined by −15.04 ms² in the placebo group (P=0.08). The high frequency/LF ratio in the upright position increased by 0.35 in the ALA group, whereas it declined by −0.42 in the placebo group (P=0.06). There were no differences between the two groups regarding rates of adverse events. CONCLUSION: Although a slight improvement tendency was seen in HRV in the ALA group, there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial. However, the high oral dose of ALA was well-tolerated.

Tratamientos farmacológicos en pacientes con síndrome de boca urente: revisión sistemática / Pharmacologic treatment of burning mouth syndrome: a systematic review

El objetivo fue determinar mediante una revisión sistemática, cuáles tratamientos farmacológicos para el Síndrome de Boca Urente (SBU) logran una reducción de síntomas, según Escala Visual Análoga (EVA). Se realizó una búsqueda bibliográfica en la bases de datos PubMed y SciELO, Trip Database, Scopus Database, EBSCO host y LILACS entre el 2005 y 2015. De 72 artículos, se seleccionaron un total de 11. Los tratamientos sistémicos usados fueron, Hipericum perforatum, Catuama, Clonazepam, Ácido alfa lipoico y Lafutidina. Entre los tratamientos tópicos, Aceite de oliva virgen enriquecido con licopeno, Lisozima lactoperoxidasa, Clonazepam y Capsaicina. Los fármacos que obtuvieron mejores resultados para el tratamiento del SBU fueron Lafutidina, Catuama, Clonazepam tópico y sistémico, y en menor grado Capsaicina.

The aim of this study was to determine through a systematic review, which is the best drug treatment for burning mouth syndrome (SBU), measured on a Visual Analogue Scale. A scientific literature search was conducted in PubMed and SciELO, Trip Database, Database Scopus, EBSCO host and LILACS data between 2005 and 2015. Of a total of 72 articles, 11 were included for analysis. Systemic treatments were Lycopene-enriched virgin olive oil, Hypericum perforatum, Catuama, Clonazepam, Alpha lipoic acid; topical treatments were Lysozyme lactoperoxidase, Clonazepam, Capsaicin and Lafutidine. The best results obtained were with Lafutidine, Catuama, topical and systemic Clonazepam, and to a lesser degree Capsaicin.

Antioxidant therapy in the elderly with tinnitus / Efeito da terapia com antioxidantes sobre o zumbido em idosos

ABSTRACT INTRODUCTION: Several approaches have been tried for the treatment of tinnitus, from cognitive-behavioral therapies and sound enrichment to medication. In this context, antioxidants, widely used in numerous areas of medicine, appear to represent a promising approach for the control of this symptom, which often is poorly controlled. OBJECTIVE: To evaluate the effects of antioxidant therapy for tinnitus in a group of elderly patients. METHODS: Prospective, randomized, double-blinded, placebo-controlled clinical trial. The sample consisted of 58 subjects aged 60 years or older, with a complaint of tinnitus associated with sensorineural hearing loss. These individuals completed the Tinnitus Handicap Inventory (THI) questionnaire before and after six months of therapy. The treatment regimens were: Ginkgo biloba dry extract (120 mg/day), a-lipoic acid (60 mg/day) + vitamin C (600 mg/day), papaverine hydrochloride (100 mg/day) + vitamin E (400 mg/day), and placebo. RESULTS: There was no statistically significant difference between THI by degree (p = 0.441) and by score (p = 0.848) before and after treatment. CONCLUSION: There was no benefit from the use of antioxidant agents for tinnitus in this sample.

Resumo Introdução: Uma série de abordagens terapêuticas tem sido empregada no tratamento do zumbido, desde terapias cognitivo-comportamentais e de enriquecimento sonoro até terapias medicamentosas. Nesse contexto, os agentes antioxidantes, amplamente utilizados em diversas áreas da medicina, parecem representar uma perspectiva promissora para o controle desse sintoma, que muitas vezes tem um controle clínico insatisfatório. Objetivo: Avaliar os efeitos da terapia com agentes antioxidantes sobre o zumbido em um grupo de pacientes idosos. Método: Ensaio clínico prospectivo, randomizado, duplo-cego e controlado por placebo. A amostra composta de 58 indivíduos com 60 anos ou mais, com queixa clínica de zumbido associado à perda auditiva, do tipo neurossensorial, em graus variados. Esses indivíduos foram submetidos ao questionário THI (Tinnitus Handicap Inventory) antes e após 6 meses de uso da medicação. Os esquemas terapêuticos foram os seguintes: extrato seco de Ginkgo biloba(120 mg/dia), ácido a-lipóico (60 mg/dia) + vitamina C (600 mg/dia), cloridrato de papaverina(100 mg/dia) + vitamina E (400 mg/dia) e placebo. Resultados: O THI após o tratamento foi estatisticamente igual ao THI antes do tratamento, tanto em graus (p = 0,441) quanto em escores (p = 0,848). Conclusão: Não se verificou benefício estatisticamente significativo com o uso de agentes antioxidantes para o zumbido dos indivíduos avaliados.

Efeito antipsicótico da associação da clorpromazina e ácido lipóico em modelo de esquizofrenia induzido pela cetamina em ratos

A esquizofrenia, síndrome neuropsiquiátrica caracterizada por comprometimento das funções cerebrais, apresenta, além de sintomas comportamentais, alterações eletroencefalográficas, está associada a uma desregulação das respostas imunológicas e componente oxidativo. No entanto, o papel do dano oxidativo nas alterações eletroencefalográficas presentes na esquizofrenia não está completamente esclarecido. Desta maneira, este estudo teve como objetivo avaliar os efeitos antipsicóticos da associação de clorpromazina (CP) e ácido lipóico (ALA), em modelo de esquizofrenia induzido por cetamina (KET), em ratos. Foram utilizados ratos Wistar machos (200-300 g), tratados durante 10 dias e divididos em dois protocolos experimentais. No primeiro, os animais foram divididos em quatro grupos (n = 10) e tratados com solução salina (controle) ou cetamina (10, 50 ou 100 mg/kg). No segundo, os animais foram divididos em nove grupos (n = 10), tratados com solução salina (controle), ácido lipóico (100 mg/kg), cetamina (10 mg/kg), clorpromazina (1 ou 5 mg/kg) sozinha ou associada a cetamina (CP1 ou CP5+KET) ou associada ao ácido lipóico (ALA+CP1 ou CP5+KET)...

Schizophrenia, a neuropsychiatric syndrome characterized by brain functions impairment, presents besides the behavioral symptoms, electroencephalographic changes and it is associated with a dysregulation of immune responses and oxidative component. However, the role of the inflammatory and oxidative damage on the electroencephalographic alterations present in schizophrenia was not completely clarified. Thus, this study aimed to investigate the electroencephalographic, behavioural and neurochemical effects in the hippocampus of rats treated with chlorpromazine alone or associated with lipoic acid in the model of schizophrenia induced by ketamine. However, the role of oxidative damage in electroencephalographic changes present in schizophrenia is not fully understood. As a result, this study aimed to evaluate the effects of the antipsicotics association of chlorpromazine (CP) and lipoic acid (ALA) in the schizophrenia model induced by ketamine (KET) in rats. Wistar male rats (200-300 g) were tested. They were treated for 10 days and divided into two experimental protocols: At first the animals were divided into 4 groups (n = 10) and treated with saline (control) or ketamine (10, 50, or 100 mg/kg). In the second, the animals were divided into 9 groups (n = 10) treated with saline (control), lipoic acid (100mg/kg), ketamine (10mg/kg) and chlorpromazine (1 or 5 mg/kg) alone or and ketamine (CP1 and CP5+KET) or associated with lipoic acid (ALA+CP1 and CP5+KET)...

alpha-Lipoic Acid Inhibits Expression of IL-8 by Suppressing Activation of MAPK, Jak/Stat, and NF-kappaB in H. pylori-Infected Gastric Epithelial AGS Cells

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.

Comparison of R(+)-α-lipoic acid exposure after R(+)-α-lipoic acid 200 mg and 300 mg and thioctic acid 600 mg in healthy Korean male subjects

Alpha-lipoic acid, a physiological form of thioctic acid, is a strong antioxidant that relieves diabetic neuropathic symptoms. R(+)-α-lipoic acid shows superior antioxidative effects to its racemate. We compared the pharmacokinetics (PKs) and tolerability of R(+)- and S(-)-α-lipoic acid after a single oral dose of R(+)-α-lipoic acid, Dexid®, and its racemate, thioctic acid in healthy male subjects. We used an open-label, randomized, single-dose, three-treatment, parallel study design to compare the PK exposure of the active form, R(+)-α-lipoic acid. Thirty subjects completed the study with no clinically relevant safety issues. The peak concentrations (C(max), mean±SD) of R(+)-α-lipoic acid after doses of R(+)-α-lipoic acid 200 mg, 300 mg and thioctic acid 600 mg were 4186.8±1956.7, 6985.6±3775.8 and 6498.4±3575.6 µg/L, respectively, and the areas under the plasma concentration-time curve from 0 to the last measurable concentration (AUC(last)) were 1893.6±759.4, 3575.2±1149.2 and 3790.0±1623.0 µg·h⁻¹·L⁻¹, respectively. The geometric mean ratio and 90% confidence intervals of R(+)-α-lipoic acid 200 mg to thioctic acid 600 mg for the C(max) and AUC(last) were 0.71 (0.43–1.15) and 0.51 (0.37–0.70), respectively. The corresponding R(+)-α-lipoic acid 300 mg to thioctic acid 600 mg values were 1.11 (0.68-1.80) and 0.97 (0.71-1.34), respectively. In conclusion, R(+)-α-lipoic acid 300 mg showed PK characteristics similar to those of thioctic acid 600 mg and both formulations were well tolerated.

Does alfa lipoic acid prevent liver from methotrexate induced oxidative injury in rats?

PURPOSE: To determine the antioxidant and anti-inflammatory effects of alfa lipoic acid (ALA) on the liver injury induced by methotrexate (MTX) in rats. METHODS: Thirty two rats were randomly assigned into four equal groups; control, ALA, MTX and MTX with ALA groups. Liver injury was performed with a single dose of MTX (20 mg/kg) to groups 3 and 4. The ALA was administered intraperitonealy for five days in groups 2 and 4. The other rats received saline injection. At the sixth day the rats decapitated, blood and liver tissue samples were removed for TNF-α, IL-1β, malondialdehyde, glutathione, myeloperoxidase and sodium potassium-adenosine triphosphatase levels measurement and histological examination. RESULTS: MTX administration caused a significant decrease in tissue GSH, and tissue Na+, K+ ATPase activity and which was accompanied with significant increases in tissue MDA and MPO activity. Moreover the pro-inflammatory cytokines (TNF-α, IL- β) were significantly increased in the MTX group. On the other hand, ALA treatment reversed all these biochemical indices as well as histopathological alterations induced by MTX. CONCLUSION: Alfa lipoic acid ameliorates methotrexate induced oxidative damage of liver in rats with its anti-inflammatory and antioxidant effects. .