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Int. braz. j. urol ; 45(4): 815-824, July-Aug. 2019. tab, graf
Article in English | LILACS | ID: biblio-1019894


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.

Animals , Male , Spermatozoa/drug effects , Testis/drug effects , Thioctic Acid/pharmacology , Diabetes Mellitus, Experimental/pathology , Epididymis/drug effects , Antioxidants/pharmacology , Sertoli Cells , Sperm Count , Sperm Motility/drug effects , Spermatogenesis/drug effects , Spermatogenesis/physiology , Spermatozoa/physiology , Testis/physiopathology , Testis/pathology , Immunohistochemistry , Random Allocation , Reproducibility of Results , Rats, Wistar , Diabetes Mellitus, Experimental/physiopathology , Epididymis/pathology
Yonsei Medical Journal ; : 260-264, 2016.
Article in English | WPRIM | ID: wpr-220773


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.

Enzyme-Linked Immunosorbent Assay , Epithelial Cells/metabolism , Gastric Mucosa/drug effects , Gene Expression Regulation, Bacterial , Helicobacter Infections/immunology , Helicobacter pylori/drug effects , Humans , 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/pharmacology
Rev. méd. Chile ; 142(12): 1553-1564, dic. 2014. ilus, graf, tab
Article in Spanish | LILACS | ID: lil-734862


Background: Liver fibrogenic processes are related to cellular redox state. Glutathione (GSH) is the major cellular antioxidant. GSH induced activation could be related to antifibrogenic effects. Aim: To explore the association between the antifibrogenic effect and pro-antioxidant mechanisms of alpha-lipoic acid (ALA) and pirfenidone (PFD). Material and Methods: HepG2 cells and primary HSC cultures were exposed to menadione 0.1 μM (MEN) as oxidative stress inducer and treated to ALA (5 mM) or PFD (10 μM, 100 μM y 1000 μM). Results: In HSC, PFD decreased cell proliferation and the expression of COL1A1, TGF-β1, TIMP1, IL6, TNFα and MCP1 induced by MEN. Furthermore it was confirmed that ALA and PFD activate diverse antioxidants mediators, however MEN decreases this response. Then, MEN, ALA and PFD induce an antioxidant response, the first one as a response to injury and the latter two as pro-antioxidant inducers. Therefore, when cells are exposed to oxidative stress, endogenous systems activate a battery of mediators that increase the antioxidant potential. When these cells are treated with ALA and PFD, de novo formation of protective genes decreases since previous elicited protection induced in response to injury, enhance ALA and PFD effects. Conclusion: Regardless of the route of action, ALA and PFD induce the biosynthesis of antioxidants mediators which is associated with modulation of fibrogenic processes.

Humans , Antioxidants/pharmacology , Hepatocytes/drug effects , Oxidative Stress/drug effects , Pyridones/pharmacology , Thioctic Acid/pharmacology , Cells, Cultured , Oxidation-Reduction/drug effects
Invest. clín ; 53(3): 250-261, sep. 2012. ilus
Article in English | LILACS | ID: lil-676476


Aging and reduced longevity are due in part to the action of free radicals (FR). Melatonin (Mel) and thioctic acid (TA) are effective in protecting against the damage caused by FR. In this study, the effect of Mel and TA on the life cycle of Drosophila melanogaster was determined. We used a control group of flies, another group that was provided with Mel (0.43 mM) throughout their life cycle (Mel-c), a third group received Mel upon reaching adulthood (Mel-a) and two groups were fed with TA (2.15 mM) in the same manner (TA-c and TA-a). The number of eclosed, survival, phenotype changes, motor activity and the content of malondialdehyde (MDA) was evaluated in each group. Mel-c increased the eclosion rate and the motor activity of the flies. Mel-c and Mel-a increased the life span and decreased the concentrations of MDA. By contrast, TA-c diminished the eclosion rate, produced phenotypic changes and increased MDA levels and motor activity of the flies. TA-a extended the life span of flies, and did not alter MDA levels and motor activity when compared with the control group. In conclusion, Mel mitigated the effects caused by FR generated during aging, while TA-c increased lipid peroxidation and altered the phenotype of flies.

El envejecimiento y la disminución de la longevidad se deben, en parte, a la acción de los radicales libres (RL). La melatonina (Mel) y el ácido tióctico (AT) son antioxidantes efectivos contra el daño ocasionado por los RL. En este estudio se determinó el efecto de la Mel y el AT en el ciclo de vida de la Drosophila melanogaster. Se utilizó un grupo de moscas control, otro grupo al que se le suministró Mel (0,43 mM) durante todo su ciclo de vida (Mel-c), un tercer grupo recibió Mel al alcanzar la adultez (Mel-a) y dos grupos a los que se le suministró AT (2,15 mM) de la misma manera (AT-c y AT-a). Se evaluó el número de eclosionados, la sobrevida, el fenotipo, la actividad motora y el contenido de malondialdehído (MDA) en cada uno de los grupos. Mel-c incrementó la tasa de eclosión y aumentó la actividad motora. Mel-a y Mel-c aumentaron la sobrevida y disminuyeron las concentraciones de MDA. Por el contrario, el AT-c disminuyó la tasa de eclosión, produjo cambios fenotípicos, no afectó la sobrevida de las moscas, aumentó los niveles de MDA y la actividad motora. El AT-a extendió la duración de la vida de los animales, no alteró los niveles de MDA, ni la actividad motora al comparar con el grupo control. En conclusión, la Mel mitigó los efectos causados por los RL generados durante el envejecimiento, mientras que el AT-c aumentó la peroxidación lipídica y alteró el fenotipo de las moscas.

Animals , Female , Humans , Male , Antioxidants/pharmacology , Drosophila melanogaster/drug effects , Longevity/drug effects , Melatonin/pharmacology , Thioctic Acid/pharmacology
Arq. neuropsiquiatr ; 69(2b): 360-364, 2011. ilus, tab
Article in English | LILACS | ID: lil-588098


Pilocarpine-induced seizures can be mediated by increases in oxidative stress and by cerebral amino acid changes. The present research suggests that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the lipoic acid (LA) effects in glutamate and taurine contents in rat hippocampus after pilocarpine-induced seizures. Wistar rats were treated intraperitoneally (i.p.) with 0.9 percent saline (Control), pilocarpine (400 mg/kg, Pilocarpine), LA (10 mg/kg, LA), and the association of LA (10 mg/kg) plus pilocarpine (400 mg/kg), that was injected 30 min before of administration of LA (LA plus pilocarpine). Animals were observed during 24 h. The amino acid concentrations were measured using high-performance liquid chromatograph (HPLC). In pilocarpine group, it was observed a significant increase in glutamate content (37 percent) and a decrease in taurine level (18 percent) in rat hippocampus, when compared to control group. Antioxidant pretreatment significantly reduced the glutamate level (28 percent) and augmented taurine content (32 percent) in rat hippocampus, when compared to pilocarpine group. Our findings strongly support amino acid changes in hippocampus during seizures induced by pilocarpine, and suggest that glutamate-induced brain damage plays a crucial role in pathogenic consequences of seizures, and imply that strong protective effect could be achieved using lipoic acid through the release or decrease in metabolization rate of taurine amino acid during seizures.

As convulsões induzidas pela pilocarpina podem ser mediadas através do aumento do estresse oxidativo cerebral e das alterações na concentração dos aminoácidos. O presente estudo sugere que compostos antioxidantes podem produzir neuroproteção contra a neurotoxicidade em nível celular causada pelas convulsões. O objetivo deste estudo foi avaliar os efeitos do ácido lipóico (AL) no conteúdo de glutamato e taurina no hipocampo de ratos durante convulsões induzidas por pilocarpina. Ratos Wistar foram tratados por via intraperitoneal com solução salina 0,9 por cento (controle), pilocarpina (400 mg/kg, pilocarpina), AL (10 mg/kg) e com a associação de AL (10 mg/kg); 30 min após com pilocarpina (400 mg/kg), que foi injetada 30 min após a administração de AL (AL + pilocarpina). Os animais foram observados durante 24 horas. As concentrações de aminoácidos foram determinadas por HPLC. No hipocampo dos ratos do grupo pilocarpina foi observado um aumento significativo de 37 por cento na concentração de glutamato e uma diminuição de 18 por cento no nível de taurina, quando comparado ao grupo controle. O pré-tratamento com o antioxidante reduziu significativamente o nível de glutamato em 28 por cento e aumentou em 32 por cento os níveis de taurina no hipocampo dos ratos, quando comparado ao grupo pilocarpina. Nossos resultados sugerem que ocorrem alterações na concentração dos aminoácidos no hipocampo de ratos durante as convulsões induzidas por pilocarpina, e que o glutamato pode desempenhar um papel crucial na fisiopatologia das convulsões, e que o efeito protetor poderia ser alcançado com pré-tratamento com ácido lipóico, provavelmente pelo aumento da liberação ou redução da taxa de metabolização dos aminoácidos durante as convulsões.

Animals , Male , Rats , Antioxidants/pharmacology , Glutamic Acid/metabolism , Hippocampus/drug effects , Seizures/metabolism , Taurine/metabolism , Thioctic Acid/pharmacology , Chromatography, High Pressure Liquid , Hippocampus/chemistry , Pilocarpine , Rats, Wistar , Seizures/chemically induced , Seizures/drug therapy
Arq. neuropsiquiatr ; 68(4): 586-591, Aug. 2010. graf, tab
Article in English | LILACS | ID: lil-555239


In the present study we investigated the effects of lipoic acid (LA) on acetylcholinesterase (AChE), glutathione peroxidase (GPx) and Na+, K+-ATPase activities in rat hippocampus during seizures. Wistar rats were treated with 0.9 percent saline (i.p., control group), lipoic acid (20 mg/kg, i.p., LA group), pilocarpine (400 mg/kg, i.p., P400 group), and the association of pilocarpine (400 mg/kg, i.p.) plus LA (20 mg/kg, i.p.), 30 min before of administration of P400 (LA plus P400 group). After the treatments all groups were observed for 1 h. In P400 group, there was a significant increase in GPx activity as well as a decrease in AChE and Na+, K+-ATPase activities after seizures. In turn, LA plus P400 abolished the appearance of seizures and reversed the decreased in AChE and Na+, K+-ATPase activities produced by seizures, when compared to the P400 seizing group. The results from the present study demonstrate that preadministration of LA abolished seizure episodes induced by pilocarpine in rat, probably by increasing AChE and Na+, K+-ATPase activities in rat hippocampus.

No presente estudo nós investigamos os efeitos do ácido lipóico (AL) sobre as atividades da acetilcolinesterase (AChE), da glutationa peroxidase (GPx) e da Na+, K+-ATPase no hipocampo de ratos durante crises convulsivas. Ratos Wistar foram tratados com solução salina a 0,9 por cento (i.p., grupo controle), ácido lipóico (20 mg/kg, i.p., grupo AL), pilocarpina (400 mg/kg, i.p., grupo P400), e a associação de AL (20 mg/kg, i.p.) com a pilocarpina (400 mg/kg, i.p.), 30 min antes da administração de pilocarpina (grupo AL + P400). Após os tratamentos todos os grupos foram observados durante 1 h. No grupo P400, houve um aumento significativo na atividade da GPx, assim como uma diminuição das atividades da AChE e Na+, K+-ATPase. Por sua vez, o pré-tratamento com AL aboliu o aparecimento de convulsões e reverteu a diminuição das atividades da AChE e da Na+, K+-ATPase causadas pelas convulsões, quando comparada com o grupo P400 sozinho. Os resultados do estudo demonstram que o pré-tratamento com AL aboliu os episódios de convulsão induzido pela pilocarpina em ratos, provavelmente por meio do aumento das atividades das enzimas AChE e Na+, K+-ATPase no hipocampo de ratos.

Animals , Male , Rats , Acetylcholinesterase/metabolism , Antioxidants/pharmacology , Glutathione Peroxidase/metabolism , Hippocampus/enzymology , Seizures/enzymology , Sodium-Potassium-Exchanging ATPase/metabolism , Thioctic Acid/pharmacology , Hippocampus/drug effects , Pilocarpine , Rats, Wistar , Seizures/chemically induced
Arq. neuropsiquiatr ; 68(3): 362-366, June 2010. ilus, graf
Article in English | LILACS | ID: lil-550266


The purposes of the present study were to verify monoamines (dopamine (DA), norepinephrine (NE), serotonin (5-HT)), and their metabolites (3,4-hydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA)) contents in rat hippocampus after lipoic acid (LA) administration. Wistar rats were treated with 0.9 percent saline (i.p., control group) and LA (10, 20 or 30 mg/kg, i.p., LA10, LA20 and LA30 groups, respectively). After the treatments all groups were observed for 24 h. The NE and DA levels were increased only in 20 mg/kg dose of LA in rat hippocampus. Serotonin content and in their metabolite 5-HIAA levels was decreased in same dose of LA. On the other hand, in DOPAC and HVA levels did not show any significant change. The alterations in hippocampal monoamines can be suggested as a possible of brain mechanism of action from this antioxidant. The outcome of the study may have therapeutic implications in the treatment of neurodegenerative diseases.

O objetivo do presente estudo foi verificar a concentração das monoaminas (dopamina (DA), norepinefrina (NA), serotonina (5-HT)), e seus metabólitos (ácido 3,4-hidroxifenil (DOPAC), ácido homovanílico (HVA) e 5 ácido hydroxiindolacético (5-HIAA)) no hipocampo de ratos após administração do ácido lipóico (AL). Ratos Wistar foram tratados com solução salina 0,9 por cento (i.p., grupo controle) e AL (10, 20 ou 30 mg/kg, i.p., AL10, AL20 e AL30 grupos, respectivamente). Após os tratamentos todos os grupos foram observados durante 24 h. O conteúdo de DA no hipocampo de ratos foi aumentado apenas com AL na dose de 20 mg/kg dose. A concentração de serotonina e do seu metabólito 5-HIAA também foi diminuída com esta dose de AL. Por outro lado, os níveis de DOPAC e de HVA não mostrram nenhuma mudança significativa. As alterações na concentração das monoaminas hipocampais podem ser sugeridas como um possível mecanismo de ação cerebral deste antioxidante. O resultado do estudo pode ter implicações terapêuticas no tratamento de doenças neurodegenerativas.

Animals , Male , Rats , Antioxidants/pharmacology , Biogenic Monoamines/metabolism , Hippocampus/drug effects , Thioctic Acid/pharmacology , Hippocampus/metabolism , Rats, Wistar
Indian J Exp Biol ; 2007 Dec; 45(12): 1045-9
Article in English | IMSEAR | ID: sea-57976


Protective efficacy of DL-alpha lipoic acid on adriamycin induced hepatotoxicity was evaluated in rats. Adriamycin toxicity, induced by a single injection (ip; 15 mg/kg body wt), was expressed by an elevation in alanine transaminase, aspartate transaminase, bilirubin levels in serum and alkaline phosphatase, lactate dehydrogenase, alanine transaminase, aspartate transaminase activity in hepatic tissue. Adriamycin produced significant increase in malondialdehyde levels indicating tissue lipid peroxidation and potentially inhibiting the activity of antioxidant, reduced glutathione and antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase. The present results showed that pretreatment with lipoic acid [75 mg/kg body wt/day (ip), 24 h prior to administration of adriamycin] significantly restored various cellular activity suggesting the antioxidant potential of lipoic acid in ameliorating the hepatotoxicity induced by adriamycin.

Animals , Antibiotics, Antineoplastic/toxicity , Antioxidants/pharmacology , Doxorubicin/toxicity , Lipid Peroxidation/drug effects , Liver Diseases/chemically induced , Male , Protective Agents/pharmacology , Rats , Rats, Wistar , Thioctic Acid/pharmacology
Article in English | WPRIM | ID: wpr-37550


The migration of vascular smooth muscle cells (VSMCs) into the intima, an important step in injury-induced neointimal hyperplasia, requires the activation of nuclear factor-kappaB (NF-kappaB) and the consequent up-regulation of matrix metalloproteinase-9 (MMP-9). This study was undertaken to test for a possible effect of alpha-lipoic acid (ALA), a potent inhibitor of NF-kappaB, on MMP-9 expression. ALA inhibited high-glucose- and TNF-alpha-stimulated VSMC migrations in vitro. It also inhibited high-glucose- and TNF-alpha-induced increases in MMP-9 expression. The activity of MMP-9-promoter constructs with mutations in the NF-kappaB binding site was not inhibited by ALA, indicating an involvement of the NF-kappaB signaling pathway in the ALA-specific inhibition of MMP-9. These data suggest the possibility that ALA may be useful for the prevention of neointimal hyperplasia after angioplasty, by inhibiting the NF-kappaB/ MMP-9 pathway, especially with hyperglycemia.

Thioctic Acid/pharmacology , Rats, Sprague-Dawley , Rats , Promoter Regions, Genetic/genetics , NF-kappa B/metabolism , Muscle, Smooth, Vascular/cytology , Matrix Metalloproteinase 9/genetics , Male , Gene Expression/drug effects , Cells, Cultured , Cell Movement/drug effects , Animals
Indian J Exp Biol ; 2004 Mar; 42(3): 279-82
Article in English | IMSEAR | ID: sea-60407


alpha-Lipoic acid treatment (100 mg/kg/day for 2 weeks after 6 weeks of untreated diabetes) of streptozotocin diabetic rats partially but significantly reversed both reduced contractile response of distal colon to acetylcholine and delayed transit of charcoal meal in small intestine compared to diabetic control. These effects of alpha-Lipoic acid were associated with complete reversal of diabetes induced increased plasma lipid peroxidation level. alpha-Lipoic acid had no effect on any of the parameters measured in non-diabetic rats. These findings demonstrate contribution of oxidative stress in the development of physiological changes of gut in diabetes.

Acetylcholine/metabolism , Animals , Antioxidants/pharmacology , Body Weight , Colon/drug effects , Diabetes Mellitus, Experimental , Female , Intestine, Small/metabolism , Intestines/drug effects , Lipid Peroxidation , Male , Oxidative Stress , Rats , Rats, Wistar , Streptozocin , Thioctic Acid/pharmacology
Yonsei Medical Journal ; : 776-788, 2004.
Article in English | WPRIM | ID: wpr-197581


Sulfur is an essential element for the entire biological kingdom because of its incorporation into amino acids, proteins and other biomolecules. Sulfur atoms are also important in the iron-containing flavoenzymes. Unlike humans, plants can use inorganic sulfur to synthesize sulfur-containing amino acids. Therefore, plants are an important source of sulfur for humans. Sulfur-containing compounds are found in all body cells and are indispensable for life. Some of sulfur-containing antioxidant compounds are, cysteine, methionine, taurine, glutathione, lipoic acid, mercaptopropionylglycine, N-acetylcysteine, and the three major organosulfur compounds of garlic oil, diallylsulfide, diallyldisulfide and diallyltrisulfide. In a comparison of the structure-function relationship among these sulfur-containing antioxidant compounds, dihydrolipoic acid (the reduced form of LA) is the most effective antioxidant. Dihydrolipoic acid contains two sulfhydryl groups and can undergo further oxidation reaction to form lipoic acid. The antioxidative activities of sulfur-containing compounds follow a general trend, the more highly reduced forms are stronger antioxidants and the number of sulfur atoms determine, at least in part, their modulatory activites on the glutathione related antioxidant enzymes. In this article, the antioxidant effects and the antioxidative activities, of sulfur-containing amino acids, are reviewed. In addition, the general antioxidant effects and the structure-function relationship of some sulfur-containing compounds are also reviewed.

Acetylcysteine/pharmacology , Amino Acids, Sulfur/pharmacology , Antioxidants/pharmacology , Cysteine/pharmacology , Glutathione/pharmacology , Methionine/pharmacology , Structure-Activity Relationship , Taurine/pharmacology , Thioctic Acid/pharmacology , Tiopronin/pharmacology
Acta physiol. pharmacol. ther. latinoam ; 48(3): 137-45, 1998. tab, graf
Article in Spanish | LILACS | ID: lil-216881


Se estudió el efecto de la intoxicación crónica con hexaclorobenceno en ratas, con y sin administración simultánea de tioctamida. En el grupo que recibió hexaclorobenceno solo, se produjo el esperado desarrollo de porfiria incrementándose la excreción urinaria y el contenido hepático de porfirinas y disminuyendo la actividad Uroporfirinógeno decarboxilasa. El contenido hepático de dienos conjugados no varió, en tanto que el de malondialdehido se incrementó en un grado estadísticamente no significativo. Estos resultados indicarían la existencia de un ligero proceso de peroxidación lipídica. La tioctamida (25 mg/Kg de peso) produjo efectos nocivos antes que protectores, detectados por un aumento de la actividad transaminasa glutámico pirúvica y una inhibición a nivel de la primera etapa de la Uroporfirinógeno decarboxilasa. Los resultados indicarían que: 1) altas dosis de tioctamida producen un decremento en la actividad Uroporfirinógeno decarboxilasa, enmascarando quizás su posible efecto protector frente a la acción del hexaclorobenceno por radicales libres; 2) la Uroporfirinógeno decarboxilasa es un parámetro más sensible que la medición de dienos conjugados o de melondialdehido para ensayar la producción de radicales libres por acción del hexaclorobenceno in vivo. De ser así, la tioctamida, ensayada a dosis menores y no tóxicas, a través de su habilidad como atrapante de radicales libres, quizás pueda proteger contra la acción del hexaclorobenceno.

Rats , Animals , 5-Aminolevulinate Synthetase/urine , Alanine Transaminase/drug effects , Amides/pharmacology , Fungicides, Industrial/toxicity , Hexachlorobenzene/toxicity , Lipid Peroxidation/drug effects , Liver/chemistry , Porphobilinogen/urine , Porphyrins/urine , Thioctic Acid/pharmacology , Uroporphyrinogen Decarboxylase/drug effects , Alanine Transaminase/metabolism , Free Radicals/metabolism , Liver/enzymology , Rats, Wistar , Time Factors , Uroporphyrinogen Decarboxylase/drug effects
Acta gastroenterol. latinoam ; 27(1): 31-7, mar. 1997. ilus, tab, graf
Article in English | LILACS | ID: lil-196661


Thioctic acid, a sulfhydryl agent, given orally macroscopically protected the gastric mucosa from 96 percent ethanol-induced lesions in a dose-and time dependent fashion. The inhibition of the lesions was 56.0 and 90.3 percent at doses of 25 and 50 mg/Kg, respectively. The duration of its protective effect was appoximately 120 minutes. Histopathologically, the oral administration of thioctic acid prevented necrotic mucosal lesions in the deeper part of the mucosa but did not protect the surface epithelial cells against ethanol challenge. Gastric motility measured by a ballon method, was dose-dependently inhibited by the oral administration of thioctic acid. Thioctic acid protection was suppressed by pretreatment with indomethacin (30 mg/Kg), a cyclooxygenase inhibitor, and iodoacetamide (100 mg/Kg), a sulfhydryl bloker. The gastric motility inhibited by oral thioctic acid was not reversed by indomethacin or iodoacetamide. These doses of indomethacin or iodomethamide were administered because previously they had been used to suppress endogenous prostagladins, and nonprotein sulfhydryls of the gastric mucosa, respectively. There was an increase in the fluid volume retained in the gastric lumen for thioctic acid (50 mg/Kg) at 30,60,90, and 120 minutes after administration. There was an increase in the mucus volume retained in the gastric lumen for thioctic acid (50, 25 mg/Kg) at 120 minutes after administration. The lesion area in the rats treated with 70 mul of vehicle and in the rats treated with 250 mul of vehicle were significantly higher than in the rats treated with 450 mul of vehicle. The present study suggests that thioctic acid administered orally, affered protection to the rat gastric mucosa against 96 percent ethanol-induced lesions. This protective effect appears to be dependent on prostagladin-and sulfhydryl-sensitive mechanisms, together with an increase in both the fluid volume and the mucus volume retained in the gastric lumen, and is not associated with the inhibition of gastric motor activity.

Rats , Female , Animals , Ethanol/toxicity , Gastric Mucosa/injuries , Mucus/drug effects , Prostaglandins/physiology , Sulfhydryl Compounds/physiology , Thioctic Acid/pharmacology , Analysis of Variance , Ethanol/toxicity , Gastric Mucosa/drug effects , Gastric Mucosa/metabolism , Gastrointestinal Motility/drug effects , Indomethacin/pharmacology , Iodoacetamide/pharmacology , Mucus/metabolism , Rats, Wistar , Time Factors
Acta gastroenterol. latinoam ; 26(3): 167-171, 1996. ilus, tab
Article in English | LILACS | ID: lil-186206


Background/Aims: The gastric protective effect of thioctic acid, a sulfhydryl compund, against chemically induced mucosal lesions has not been reported. Methods: Fasted Wistar rats (24 h) were treated (gavage administration) with graded doses of thiotic acid (12.5, 25, 37.5, 50 mg/kg) followed 0.5 h later by the gavage administration of 1 ml 96 per cent ethanol or intraperitoneal administered indomethacin. The gastric mucosa was examined grossly and histologically for an evaluation of the lesions. Results: Pretreatment of rats with thotic acid has shown a significant decline in the mean number, size, incidence and severity of mucosal lesions induced by both ethanol and indomethacin. Conclusions: This is the first evidence that thiotic acid protects the rat gastric mucosa against chemically induced damage. Its is speculated that this finding may prove to be important in the development of improved therapies for the prevention and treatment of gastric ulcers in humans.

Rats , Animals , Female , Gastric Mucosa/drug effects , Thioctic Acid/pharmacology , Ethanol , Gastric Mucosa/pathology , Indomethacin , Rats, Wistar , Stomach Diseases/chemically induced
Medicina (B.Aires) ; 49(4): 336-40, 1989. ilus
Article in Spanish | LILACS | ID: lil-86884


En este estudio se determina in vivo la quimioluminescencia del intestino de rata sometido a isquemia provocada por una ligadura oclusiva y luego durante la reperfusión al desligar el órgano. La quimioluminescencia del órgano en función del tiempo, en animales sometidos a 2, 5 y 10 minutos de isquemia tiende a disminuir rápidamente. En intestinos de ratas ligados durante 2 minutos y luego desligados, comparados con intestinos no ligados, se muestra un exceso medio de quimioluminescencia del 44% aproximadamente luego de 2 a 3 minutos de iniciada la reperfusión. Este exceso inicial de quimioluminescencia se mantiene entre los primeros 10 a 20 minutos posteriores a la desligadura, no habiéndose registrado períodos más prolongados. la administración de un atrapador de radicales libres, ácido tióctico 100 mg/kg, i.p. evita o reduce el exceso de quimioluminescencia descripto, por un período de por lo menos 20 minutos. Estos datos concuerdan con la sugerencia de que la generación excesiva de radicales del oxígeno tiene lugar in vivo desde los minutos iniciales de la reperfusión y puede ser la consecuencia de cambios enzimáticos producidos muy rápidamente durante el anterior período hipóxico

Rats , Animals , Free Radicals , Intestines/blood supply , Luminescence , Reperfusion Injury , Analysis of Variance , Intestines/surgery , Ligation , Rats, Wistar , Thioctic Acid/pharmacology , Time Factors
Indian J Lepr ; 1985 Oct-Dec; 57(4): 728-38
Article in English | IMSEAR | ID: sea-54885


Mycobacterium leprae suspensions were prepared from infected armadillos. The M. leprae cells were inoculated into culture media containing KH2PO4 4.7. g. Na2HPO4 2 g, sodium thioglycolate 1 g, (NH4)2SO4 2 g, MgSO4 0.1 g, ferric ammonium citrate 0.05 g, and lipoic acid (thioctic acid) 0.1 g in one liter distilled water. The solution was enriched with heat killed, sonicated leprosy derived Mycobacterium X or crude mycobactin extract from M. phlei to contain + 0.2 micrograms mycobactin per 1 ml in the final medium. Twenty ml media was distributed into each of 25 ml screw cap tubes and autoclaved for 30 minutes. Positive growth was obtained from seven out of ten specimens when incubated at 34 degrees C. The cultures developed as a sediment in the liquid media, suggesting preference for microaerophylic conditions. No growth was seen on the surface of the semi-solid agar media containing the same ingredients. Latency period of growth was estimated as 10-16 days and time of division as 6 days. Subcultures were obtained. Cells were long, acid fast, arranged side by side or end to end, with a tendency to form long spiral cords or clumps when sedimented on siliconized slides. Pyridine extraction eliminated acid fastness, but not gram positivity. Cultures did not grow on Dubos, Lowenstein or 7H10 media. They produce the disease in the foot pads of mice characteristic of M. leprae. Subcultures remain dependent on the heat killed sonicated mycobacteria, or crude mycobactin extract, and reduced oxygen tension in the media. Results suggest that cultures might be identical to M. leprae.

Ammonium Sulfate/pharmacology , Animals , Armadillos , Culture Media , Leprosy/microbiology , Magnesium Sulfate/pharmacology , Mice , Mycobacterium leprae/growth & development , Oxazoles/pharmacology , Phosphates/pharmacology , Potassium/pharmacology , Potassium Compounds , Thioctic Acid/pharmacology , Thioglycolates/pharmacology