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.

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. .

Estudo do efeito do Mito-TEMPO e do ácido lipoico sobre a cardiotoxicidade da dexorrubicina / Study of the effect of weather and Mito-lipoic acid on cardiotoxicity dexorrubicina

Introdução: A doxorrubicina (DOX) é um quimioterápico antracíclico amplamente usado para o tratamento de diversos tumores humanos, entretanto, o desenvolvimento de reações adversas à droga, em particular, cardiotoxicidade, tem limitado seu uso. Embora a toxicidade cardíaca induzida pela DOX pareça ser multifatorial, a hipótese mais investigada tem sido a formação de espécies reativas de oxigênio (ROS) e há evidências apontando para as mitocôndrias cardíacas como alvos primários da toxicidade da DOX. Esse dano oxidativo pode iniciar peroxidação lipídica e pode ser potencialmente limitado pelo uso de antioxidantes. Objetivo: O objetivo do presente estudo foi avaliar a possível eficácia do ácido lipoico (AL) e do Mito-TEMPO (Mito-T) como agentes protetores contra a cardiotoxicidade induzida pela DOX in vitro e in vivo e investigar se essa proteção pode afetar a atividade antitumoral da DOX. Método e Resultados: A capacidade do AL e Mito-T eliminar radicais livres foi avaliada usando o teste do 2,2-difenil-1-picril-hidrazila (DPPH). Menor atividade antioxidante do AL (29%) comparada ao Mito-T (63%) foi observada. DOX reduziu a viabilidade de células H9c2 (CI50 = 40,83 M, IC 95% = 28,64 – 58,21 M) e aumentou a concentração de malondialdeído (MLDA), um marcador de peroxidação lipídica, confirmando a citotoxicidade induzida pela DOX in vitro. O pré-tratamento com AL ou Mito-T não promoveu proteção contra o dano induzido pela DOX in vitro. Uma única injeção intraperitoneal (i.p.) de DOX (24 mg/kg de peso corpóreo) induziu redução significante no peso corpóreo (p<0,001), elevação da atividade sérica total de creatina quinase (p<0,05) e creatina quinase-MB (p<0,05), aumento na concentração de malondialdeído em mitocôndrias (p<0,05) e tecido cardíaco (p<0,01) em camundongos da linhagem C57BL/6 após 48 horas. O pré-tratamento dos animais com Mito-T (5 mg/kg de peso corpóreo, i.p., por dois dias, 48 e 24 horas antes da DOX) reduziu significativamente a peroxidação lipídica de mitocôndrias cardíacas (p<0,01) indicando o direcionamento do antioxidante para a mitocôndria. O tratamento com Mito-T ou AL, duas vezes, 24 e uma hora antes do tratamento com DOX, inibiu a atividade sérica de creatina quinase total (p<0,05). Além disso, o tratamento de camundongos apresentando tumor B16F10 com AL não interferiu na eficácia antitumoral da DOX. Conclusão: Os dados sugerem que a combinação de AL com DOX pode ser benéfica para o tratamento de câncer, entretanto, são necessárias novas investigações para confirmar essa suposição.

Introduction: Doxorubicin (DOX) is an anthracycline chemotherapeutic that is widely used for the treatment of many human tumours, however, the development of adverse drug reactions in particular cardiotoxicity has limited its use. Although doxorubicin-induced cardiac toxicity appears to be multifactorial, the most thoroughly investigated hypothesis has been the formation of reactive oxygen species (ROS) and there is evidence pointing to cardiac mitochondria as primary targets of the toxicity of DOX. This oxidative injury can initiate lipidic peroxidation and may be potentially limited by the use of antioxidants. Aim: The aim of the present study was to evaluate the possible efficacy of lipoic acid (LA) and Mito-TEMPO (Mito-T) as a protective agent against DOX-induced cardiotoxicity in vitro and in vivo and to investigate whether this protection may affect the antitumor activity of DOX. Method and Results: Free radical scavenging capacity of LA and Mito-T was assayed using 1,1-diphenyl-2-picrylhydrazy (DPPH) assay. Lower antioxidant activity for LA (29%) compared to Mito-T (63%) were observed. DOX reduced H9c2 viability (IC50 = 40.83 M, 95% CI = 28.64 – 58.21 M) and increased the levels of malondialdehyde (MLDA), a marker of lipid peroxidation, confirming DOX-induced cytotoxicity in vitro. Pretreatment with LA or Mito-T did not provide protection against DOX-induced damage in vitro. A single intraperitoneal (i.p.) injection of DOX (24 mg/kg body weight) induced a significant reduction in body weight (p<0.001), elevation of serum activity of total creatine kinase (p<0.05) and creatine kinase-MB (p<0.05), increase in malondialdehyde levels in cardiac mitochondria (p<0.05) and cardiac tissue (p<0.01) in C57BL/6 mice after 48 hours...

Tissue response evaluation of the mucosa of the tympanic cavity of guinea pigs, when receiving biodegradable implant

PURPOSE: To evaluate the tissue response of the mucosa of the tympanic cavity of guinea pigs, when receiving biodegradable implant. METHODS: A total of 20 male guinea pigs were divided into 2 groups. After paracentesis in both ears, a biodegradable polymer of poly lactic-co-glycolic acid was implanted in only one middle ear. Histological analysis using neutrophil exudate and vascular neoformation (acute inflammation) and fibroblast proliferation and mononuclear inflammatory cells (chronic inflammation) as parameters was performed after 10 and 30 days of survival (groups 1 and 2, respectively). RESULTS: Four ears in group 1 and 7 in group 2 had an increase of neutrophil exudate. Vascular neoformation occurred in ears with or without the implant, in both groups. Fibroblast proliferation and mononuclear inflammatory cells (lymphocytes and macrophages) increased in ears with implant in group 2. CONCLUSION: The tissue response by histological analysis of the mucosa of the tympanic cavity of guinea pigs, when receiving biodegradable implant, showed no statistically significant difference between ears with or without the implant. .

Efecto del ácido tióctico en los cambios clínicos, neuroconductivos e histopatológicos de la neuropatía diabética sensitivo motora distal / Effect of thioctic acid in the clinical, histopathological and neuroconductivos the distal motor sensory diabetic neuropathy

La polineuropatía diabética es la más común de las complicaciones microvasculares de la diabetes mellitus, siendo causa importante de morbilidad y mortalidad asociada a la enfermedad. Evaluar el efecto del ácido tióctico en los cambios clínicos, neuroconductivos e histopatológicos en la neuropatía diabética sensitivo motora distal. Estudio prospectivo, longitudinal, de intervención terapéutica, en pacientes que acudieron a la consulta externa y unidad cardiometabólica del Servicio de Medicina Interna del Hospital Militar “Dr. Carlos Arvelo”, a quien se les realizó historia clínica con evaluación del score sensitivo-motor, pruebas de neuroconducción y biopsia de piel, con evaluación a la semana n° 1, 4,12, 18 y 24. 30 pacientes diabéticos con criterio clínico de neuropatía diabética sensitivo motora distal. Se observó mejoría de las parestesias a partir de la semana 12 (p <0.05) de la administración del ácido tióctico a dosis de 600mg/día por vía oral. En la neuroconducción hubo aumento de la velocidad de conducción durante el post tratamiento (p<0,05). Se realizaron 12 biopsias de piel: 2 fueron positivas (16,7%) previo tratamiento y 10 negativas (83,3%) con anticuerpo PGP 9,5. En la semana 24 post tratamiento 7 positivas (58,3%) y 5 negativas (41,7%) (p<0,05). Se demostró que el tratamiento con ácido tióctico es efectivo en mejorar los síntomas y la neuroconducción en los pacientes diabéticos con neuropatía sensitivo motora distal.

Diabetic neuropathy is the most common microvascular complication of diabetes mellitus, and a major cause of morbidity and mortality. To evaluate the effect of thioctic acid in the clinical, histopathological neuroconductive and sensory motor diabetic distal neuropathy. Prospective, longitudinal, therapeutic intervention, in patients attending the outpatient and cardiometabolic consultation Internal Medicine; an assessment of sentitivo-motor score was performed and blood chemistry was measured as well as HbA1c. Neuroconduction and skin biopsy with assessment at weeks 1, 4.12, 18 and 24 were done. 30 diabetic patients with clinical criteria of distal motor sensory neuropathy were included. The clinical symptom was paresthesia, which was present from week 12 and showed improvement (p <0.05) at weeks 18 and 24 (p<0.05). Neuroconduction was measured by increased conduction velocity post treatment (p <0.05). Biopsieswere performed in 12 patients; two were positive (16.7%) after treatment and 10 negative (83.3%) for PGP 9.5 antibody. At week 24 of treatment, 7 were positive (58.3%) and 5 negative (41.7%) (p<0.05). We demonstrated effectiveness of thioctic acid after week 12 of treatment.

A study of the antioxidant effect of alpha lipoic acids on sperm quality

OBJECTIVE: Assisted reproductive techniques are useful in helping infertile couples achieve successful conception. Initial studies have shown that sperm cryopreservation, one step in assisted reproduction, causes a dramatic reduction in sperm quality. This has been attributed to, among other things, free radical activities. The aim of the present study was to minimize this oxidative attack by adding an antioxidant into the sperm microenvironment. Alpha lipoic acids were selected for this purpose for their efficient free radical scavenging properties and solubility in lipid and aqueous phases. METHODS: For this investigation, semen from six Boer bucks was pooled. Seminal analysis of the baseline prior to incubation of samples with different concentrations of Alpha lipoic acids (0.00625, 0.0125, 0.025, 0.05, 0.1 mmol/ml) was performed, and post-seminal analysis was conducted after a one-hour incubation. The comet assay was used to observe the effect of Alpha lipoic acids on sperm DNA integrity. Statistical analysis using an unpaired t-test with a significance level of p<0.05 was then performed. RESULTS: Our results indicate that the sperm motility rate was improved after incubation with Alpha lipoic acids at a concentration of 0.02 mmol/ml. This concentration was also capable of reducing DNA damage. CONCLUSION: In conclusion, Alpha lipoic acids renders cryoprotection to sperm, thereby improving sperm quality.

Arsenic induced oxidative stress and the role of antioxidant supplementation during chelation: a review.

Arsenic is a naturally occurring metalloid, ubiquitously present in the environment in both organic and inorganic forms. Arsenic contamination of groundwater in the West Bengal basin in India is unfolding as one of the worst natural geoenvironmental disaster to date. Chronic exposure of humans to high concentration of arsenic in drinking water is associated with skin lesions, peripheral vascular disease, hypertension, Blackfoot disease and high risk of cancer The underlying mechanism of toxicity includes the interaction with the sulphydryl groups and the generation of reactive oxygen species leading to oxidative stress. Chelation therapy with chelating agents like British Anti Lewisite (BAL), sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), meso 2,3 dimercaptosuccinic acid (DMSA) etc., is considered to be the best known treatment against arsenic poisoning. The treatment with these chelating agents however is compromised with certain serious drawbacks/side effects. The studies show that supplementation of antioxidants along with a chelating agent prove to be a better treatment regimen. This review attempts to provide the readers with a comprehensive account of recent developments in the research on arsenic poisoning particularly the role of oxidative stress/free radicals in the toxic manifestation, an update about the recent strategies for the treatment with chelating agents and a possible beneficial role of antioxidants supplementation to achieve the optimum effects.

Possible protection of vitamin E and alpha-lipoic acid against early changes in alloxan diabetic rats

Diabetes mellitus is a chronic syndrome affecting carbohydrate, fat, protein and nucleic acid metabolism. The current study was undertaken to elucidate the possible role of vitamin E and alpha lipoic acid in combination as an antioxidant and a biological membrane stabilizer in the protection against early complication of diabetes. Administration of alloxan [125 mg/kg wt, i.p.] to rats resulted in hyperglycemia, hyperinsulinemia, hypercholesterolemia, hypertriglyceridemia, hyperlipidemia, increase in plasma levels of urea, blood urea nitrogen [BUN], creatinine, uric acid as well as pancreatic thiobarbituric acid reactive substances [TBARS] and glutathione [GSH] content of both liver and retina. These changes were accompanied with significant decrease in plasma total protein, tumor necrosis factor alpha [TNF alpha], hepatic catalase activity [CAT], and TBARS level of both liver and retina as compared to control group. However, plasma levels of calcium ions [Ca+2] and nitric oxide [NO] as well as pancreatic GSH content were not changed. On the other hand, the daily treatment of the diabetic rats with antioxidant mixture attained a reduction in plasma levels of glucose, cholesterol, triglycerides, total lipids, urea, BUN, creatinine, uric acid, TNF alpha, pancreatic TBARS level as well as GSH content of both liver and retina. In contrast, the daily treatment caused an increase in plasma levels of insulin, total proteins, hepatic CAT activity and pancreatic GSH content as compared to diabetic rats. However, plasma levels of Ca+2 and NO as well as TBARS content of both liver and retina were not affected. In conclusion, it is obvious from the present study results that early stage [two weeks] of diabetes induce deteriorate changes in carbohydrate, lipid, protein and nucleic acid metabolism accompanied with increasing of oxidative stress in pancreas as compared to both of liver and retina. Moreover, the data of present study indicated the effective role of vitamin E and alpha lipoic acid combination in combating the oxidative stress via its improvement to metabolism of carbohydrates, lipids, proteins and nucleic acids in addition to its free radical-scavenging and antioxidant properties

Effect of alpha lipoic acid, melatonin and trans resveratrol on intracerebroventricular streptozotocin induced spatial memory deficit in rats.

In the present study, the effect of antioxidants-alpha lipoic acid, melatonin and trans resveratrol were studied against intracerebroventricular streptozotocin induced spatial memory deficit. Male Wistar rats were injected with intracerebroventricular streptozotocin bilaterally. The rats were treated chronically with alpha lipoic acid (200 mg/kg, po), melatonin (20 mg/kg, ip) and trans resveratrol (20 mg/kg, ip) for 18 days starting from day 1 of streptozotocin injection in separate groups. The spatial memory was evaluated using the Morris water maze task. The intracerebroventricular streptozotocin rats treated with antioxidants showed significantly less spatial memory deficit both in the acquisition and probe trials as compared to the vehicle treated rats. The study demonstrated the effectiveness of alpha lipoic acid, melatonin and trans resveratrol in preventing spatial memory deficit induced by intracerebroventricular streptozotocin and it's potential in age related neurodegenerative disorders where oxidative stress is involved such as Alzheimer's disease.

Fatal mushroom poisoning caused by Amanita virosa in Thailand.

Consumption of toxic mushrooms belonging to the genus Amanita frequently leads to severe gastrointestinal distress followed by acute hepatic failure with a fatal outcome. In Thailand, valuable information as to the locally prevalent poisonous species, the preferred habitat and the management of suspected victims of intoxication is basically non-existent. We report here 5 cases of fatal poisoning with Amanita virosa having occurred in a family residing in the northeast of Thailand who as countless others had enjoyed mushroom gathering as a pasttime. Within 4 to 6 days after ingestion of the mushrooms, all had succumbed to acute hepatic failure with subsequent hepatoencephalopathy. Treatment modalities exist in the form of penicillin and silibinin, or thioctic acid administration followed by plasmapheresis. In cases taking a lethal course apparent from the results of liver biochemistry, liver transplantation is clearly indicated. In order to prevent mushroom poisoning altogether, educating the general population to that end certainly presents the method of choice.