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1.
BMJ Open ; 5(4): e006048, 2015 Apr 03.
Article in English | MEDLINE | ID: mdl-25841232

ABSTRACT

OBJECTIVE: A relation between transfusional IOL (iron overload), HFE status and oxidative damage was evaluated. DESIGN, SETTING AND PARTICIPANTS: An observational cross-sectional study involving 87 healthy individuals and 78 patients with myelodysplastic syndromes (MDS) with and without IOL, seen at University Hospital of the Federal University of Ceará, Brazil, between May 2010 and September 2011. METHODS: IOL was defined using repeated measures of serum ferritin ≥1000 ng/mL. Variations in the HFE gene were investigated using PCR/restriction fragment length polymorphism (RFLP). The biomarkers of oxidative stress (plasmatic malonaldehyde (MDA), glutathione peroxidase (GPx) and superoxide dismutase (SOD)) were determined by spectrophotometry. RESULTS: The HFE gene variations were identified in 24 patients (30.77%) and 5 volunteers (5.74%). The H63D variant was observed in 35% and the C282Y variant as heterozygous in 5% of patients with MDS with IOL. One patient showed double heterozygous variant (C282Y/H63D) and serum ferritin of 11,649 ng/mL. In patients without IOL, the H63D variant was detected in 29.34%. Serum MDA levels were highest in patients with MDS with IOL, with a significant difference when compared with patients without IOL and healthy volunteers, pointing to the relationship between IOL and oxidative stress. The GPx and SOD were also significantly higher in these patients, indicating that lipid peroxidation increase was followed by an increase in antioxidant capacity. Higher ferritin levels were observed in patients with HFE gene variation. 95.7% of patients with MDS with the presence of HFE gene variations had received more of 20 transfusions. CONCLUSIONS: We observed a significant increase in MDA levels in patients with MDS and IOL, suggesting an increased lipid peroxidation in these patients. The accumulation of MDA alters the organisation of membrane phospholipids, contributing to the process of cellular degeneration. Results show that excess iron intensifies the process of cell damage through oxidative stress. TRIAL REGISTRATION NUMBER: Local Ethics Committee (licence 150/2009).


Subject(s)
Histocompatibility Antigens Class I/genetics , Iron Overload/genetics , Myelodysplastic Syndromes/genetics , Oxidative Stress/genetics , Adult , Aged , Analysis of Variance , Biomarkers/blood , Case-Control Studies , Cross-Sectional Studies , Female , Genotype , Humans , Iron Overload/etiology , Male , Middle Aged , Mutation , Myelodysplastic Syndromes/blood , Myelodysplastic Syndromes/complications , Polymorphism, Restriction Fragment Length
2.
Rev. cuba. plantas med ; 19(2): 160-171, Apr.-June 2014.
Article in Portuguese | LILACS | ID: lil-727599

ABSTRACT

Introdução: a biodiversidade da flora mundial proporciona moléculas importantes no tratamento e na prevenção de várias enfermidades humanas, porém na maioria das vezes não são avaliadas sua toxicidade. Objetivo: avaliar a toxicidade do monoterpenóide epóxilimoneno em camundongos tratados de forma aguda com doses repetidas (25, 50 e 75mg/kg) por via oral em parâmetros bioquímicos e hematológicos. Métodos: quarenta camundongos correspondendo a quatro grupos (n=10/grupo) foram tratados, por via oral de forma aguda com doses repetidas e observados durante 14 dias, com epóxilimoneno nas doses de 25, 50 e 75 mg/kg emulsionado em Tween 80 0,05%dissolvido em solução salina 0,9 % (grupos EL25, EL50 e EL75, respectivamente), e com veículo (Tween 80, 0,05 % dissolvido em solução salina 0,9 %, grupo controle). Resultados: o tratamento não causou nenhuma morte ou sinal de toxicidade nos animais. Discussão: dessa forma, baseado nos resultados obtidos a partir dos estudos hematológicos e bioquímicos em camundongos, pode ser sugerido que a administração do epóxilimoneno não produz efeitos tóxicos sobre a maioria dos parâmetros analisados e que pode ser usado de forma segura em ensaios pré-clínicos. No entanto, mais estudos devem ser realizados para garantir que esse derivado de um monoterpeno natural seja utilizado de forma segura na indústria alimentícia e farmacêutica.


Introducción: la biodiversidad global de la flora proporciona moléculas importantes para el tratamiento y prevención de diversas enfermedades humanas, pero más a menudo no se evalúa su toxicidad. Objetivo: evaluar la toxicidad de lepóxilimoneno monoterpenoide en los ratones tratados de forma aguda con dosis repetidas (25, 50 y 75 mg/kg) por vía oral en los parámetros hematológicos y bioquímicos. Métodos: cuarenta ratones que representan cuatro grupos (n = 10/grupo) fueron tratados con dosis por vía oral de forma aguda repetida y se observaron durante 14 días com elepóxilimonenoa dosis de 25, 50 y 75 mg/kg emulsionados enTween 80 0,05 % disuelto en solución salina 0,9 % (grupos EL25, EL50 y EL75, respectivamente), y vehículo (Tween 80, 0,05 % disuelto en solución salina 0,9 %, grupo de control). Resultados: El tratamientono no causó muertes ni signos de toxicidad en animales. Discusión: de este modo, sobre la base de los resultados obtenidos a partir de los parámetros hematológicos y bioquímicos en ratones, se puede sugerir que la administración de epóxilimoneno no produce efectos tóxicos en la mayoría de los parámetros analizados y se puede utilizar de forma segura en la pre-clínica. Sin embargo, se deben realizar más estudios para asegurar que el derivado de un monoterpeno natural puede ser usado con seguridad en la industria alimentaria y farmacéutica.


Introduction: the biodiversity of global flora provides important molecules for the treatment and prevention of various human diseases, but most often their toxicities are not evaluated. Objective: evaluate the toxicity of monoterpenoid limonene epoxidein mice treated acutely with repeated doses (25, 50 and 75 mg/kg) orally on hematological and biochemical parameters. Methods: forty mice divided infour groups (n = 10/group ) were treated orally andacutely with repeated doses and observed for 14 days. The mice were treatedwith limonene epoxide administered at doses of 25, 50 and 75 mg / kg emulsified with 0.05 % Tween 80 dissolved in 0.9 % saline (groupsEL25, EL50 and EL75, respectively)and withvehicle (0.05 % Tween 80, dissolved in 0.9% saline, control group). Results: the treatment caused no deaths or signs of toxicity in the mice treated. Discussion: thus, based on the results obtained from hematological and biochemical studies in mice, it can be suggested that limonene epoxide does not produce anytoxic effect on most of the parameters analyzed, and can be safely used in pre-clinical-assays However, more studies should be conducted to ensure that this derivative of a natural monoterpenecan be safely used in thefood and pharmaceutical industry.

4.
Rev Bras Hematol Hemoter ; 35(1): 29-34, 2013.
Article in English | MEDLINE | ID: mdl-23580881

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the impact of iron overload on the profile of interleukin-10 levels, biochemical parameters and oxidative stress in sickle cell anemia patients. METHODS: A cross-sectional study was performed of 30 patients with molecular diagnosis of sickle cell anemia. Patients were stratified into two groups, according to the presence of iron overload: Iron overload (n = 15) and Non-iron overload (n = 15). Biochemical analyses were performed utilizing the Wiener CM 200 automatic analyzer. The interleukin-10 level was measured by capture ELISA using the BD OptEIAT commercial kit. Oxidative stress parameters were determined by spectrophotometry. Statistical analysis was performed using GraphPad Prism software (version 5.0) and statistical significance was established for p-values < 0.05 in all analyses. RESULTS: Biochemical analysis revealed significant elevations in the levels of uric acid, triglycerides, very low-density lipoprotein (VLDL), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), urea and creatinine in the Iron overload Group compared to the Non-iron overload Group and significant decreases in the high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Ferritin levels correlated positively with uric acid concentrations (p-value < 0.05). The Iron overload Group showed lower interleukin-10 levels and catalase activity and higher nitrite and malondialdehyde levels compared with the Non-iron overload Group. CONCLUSION: The results of this study are important to develop further consistent studies that evaluate the effect of iron overload on the inflammatory profile and oxidative stress of patients with sickle cell anemia.

5.
Rev. bras. hematol. hemoter ; 35(1): 29-34, 2013. graf, tab
Article in English | LILACS | ID: lil-670456

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the impact of iron overload on the profile of interleukin-10 levels, biochemical parameters and oxidative stress in sickle cell anemia patients. METHODS: A cross-sectional study was performed of 30 patients with molecular diagnosis of sickle cell anemia. Patients were stratified into two groups, according to the presence of iron overload: Iron overload (n = 15) and Non-iron overload (n = 15). Biochemical analyses were performed utilizing the Wiener CM 200 automatic analyzer. The interleukin-10 level was measured by capture ELISA using the BD OptEIAT commercial kit. Oxidative stress parameters were determined by spectrophotometry. Statistical analysis was performed using GraphPad Prism software (version 5.0) and statistical significance was established for p-values < 0.05 in all analyses. RESULTS: Biochemical analysis revealed significant elevations in the levels of uric acid, triglycerides, very low-density lipoprotein (VLDL), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), urea and creatinine in the Iron overload Group compared to the Non-iron overload Group and significant decreases in the high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Ferritin levels correlated positively with uric acid concentrations (p-value < 0.05). The Iron overload Group showed lower interleukin-10 levels and catalase activity and higher nitrite and malondialdehyde levels compared with the Non-iron overload Group. CONCLUSION: The results of this study are important to develop further consistent studies that evaluate the effect of iron overload on the inflammatory profile and oxidative stress of patients with sickle cell anemia.


Subject(s)
Humans , Male , Female , Interleukin-10 , Oxidative Stress , Iron Overload , Anemia, Sickle Cell , Nitric Oxide/metabolism
6.
Rev. eletrônica enferm ; 14(4): 957-964, dez. 2012.
Article in Portuguese | LILACS, BDENF - Nursing | ID: lil-693869

ABSTRACT

As cardiopatias congênitas representam anomalias que incluem defeitos estruturais e funcionais no coração, os quais necessitam precocemente de intervenção de enfermagem à beira do leito. Objetivou-se analisar pesquisas que abordassem as condutas de enfermagem à criança no pós-operatório de cirurgia cardíaca. O presente trabalho trata-se de revisão integrativa da literatura em diferentes bases de dados, utilizando os descritores: Cuidados de enfermagem, Cirurgia cardíaca e Enfermagem pediátrica. Dos onze artigos identificados e analisados na íntegra, seis corresponderam aos critérios adotados no estudo, com evidências entre os níveis II e VI. As publicações culminaram nas condutas de prevenção, avaliação e recuperação ou reabilitação. Conclui-se que este estudo contribui para assistir no desenvolvimento de planos de cuidados de enfermagem no intuito de proporcionar melhorias na prática assistencial, com base em ações de promoção à saúde, com ênfase sobre avaliação da dor, verificação da temperatura invasiva e medidas não farmacológicas para manejo da dor, entre outras...


Congenital cardiopathies represent anomalies including structural and functional heart defects, which demand early nursing intervention at the bedside. The present study aimed at analyzing studies that addressed the nursing care provided to children postoperatively following cardiac surgery. It consists of an integrative review of the literature from different databases, using the descriptors: Nursing care; Cardiac surgery; and Pediatric nursing. From the eleven articles that were identified and completely analyzed, six corresponded to the criteria adopted in the study, with evidence levels ranging from level II to level VI. The publications highlighted recommendations concerning prevention, assessment, recovery and/or rehabilitation. It is concluded that this study contributes to the development of nursing care plans to provide improvements in healthcare practices, based on actions of health promotion, with emphasis on pain assessment, verification of the internal temperature and non-pharmacological measures to cope with pain, among others...


Las cardiopatías congénitas representan anomalías que incluyen defectos cardíacos estructurales y funcionales, los cuales necesitan de pronta intervención de enfermería al pie del lecho. Se objetivó analizar investigaciones abordando las conductas de enfermería hacia niños en postoperatorio de cirugía cardíaca. Revisión integrativa de literatura según diferentes bases de datos, utilizando los descriptores: Cuidados de Enfermería, Cirugía Cardíaca y Enfermería Pediátrica. De once artículos identificados y analizados integralmente, seis correspondieron a los criterios adoptados en el estudio, con evidencias entre los niveles II y IV. Las publicaciones enfatizaron las conductas preventivas, de evaluación y recuperación o rehabilitación. Se concluye en que este estudio contribuye ayudando al desarrollo de planes de cuidados de enfermería con el objetivo de proporcionar mejorías en la práctica asistencial, con base en acciones de promoción sanitaria, con énfasis sobre la evaluación del dolor, verificación de temperatura invasiva y medidas no farmacológicas para manejo del dolor, entre otras...


Subject(s)
Humans , Child , Pediatric Nursing , Cardiac Surgical Procedures/nursing , Postoperative Period
7.
Rev. bras. ciênc. saúde ; 16(03)out. 2012.
Article in Portuguese | LILACS | ID: lil-655237

ABSTRACT

Objetivo: Avaliar a segurança da ciano-carvona por meio de estudos de toxicidade aguda e o seu potencial ansiolítico. Material e Métodos: Camundongos Swiss machos foram tratados com ciano-carvona (v.o) em doses crescentes de 25 a 2000 mg/kg e observados durante 14 dias em relação às alterações comportamentais e taxa de mortalidade. Posteriormente foram realizados exames hematológicos, bioquímicos e análise macroscópica dos principais órgãos. Além disso, outros grupos de animais foram tratados com as doses de 25, 50 e 75 mg/kg, para avaliação da atividade locomotora, do efeito ansiolítico e da coordenação motora. Resultados: No teste hipocrático, devido à ausência de mortalidade, a DL50 não foi determinada. Os sinais clínicos foram discretos, reversíveis e observados apenas nas maiores doses. Dessa forma, em relação às análises hematológicas e bioquímicas não foram verificadas alterações significativas. Nos estudos comportamentais verificou-se uma redução da atividade locomotora, um maior número de entradas nos braços abertos, bem como um maior tempo de permanência nos braços abertos, sugerindo um possível efeito ansiolítico. Em relação ao teste do rota rod não foi verificada alteração no tempo de permanência na barra giratória, bem como não foi detectado mudanças no número de quedas. Conclusão: Este estudo demonstrou que a ciano-carvona não apresenta toxicidade aguda, sugerindo um efeito ansiolítico que precisa ser melhor investigado para a elucidação do seu mecanismo de ação.


Objective: To evaluate the safety of cyano-carvone by means of acute toxicity studies and to investigate its anxiolytic potential. Material and Methods: Swiss male mice were treated with cyano-carvone (v.o) in escalating doses from 25 to 2000 mg/kg and observed for 14 days as regards behavioral changes and mortality rate. After this time period, hematological, biochemical and morphological analyses of the main macroscopic organs were carried out. In addition, other groups of animals were treated with doses of 25, 50 and 75 mg/kg in order to assess locomotor activity, anxiolytic effect and motor coordination. Results: In the Hippocratic test, the compound did not cause any deaths among the mice, thus the LD50 was not determined and clinical signs that emerged were discrete, reversible and observed only in higher doses. Accordingly, hematological and biochemical analyses did not show significant alterations. In the behavioral analysis, it was found a reduction of locomotor activity and a greater number of entries in open arms, as well as a longer time spent with open arms, suggesting an anxiolytic effect. In the Rota-rod test it was observed no change in the permanence time on the spinning rod, as well as no changes were detected for the number of falls. Conclusion: This study demonstrated that cyano-carvone has no acute toxicity, and suggests a possible anxiolytic effect that needs to be further investigated in order to elucidate its mechanism of action.

8.
Eur J Pharmacol ; 668(1-2): 65-71, 2011 Oct 01.
Article in English | MEDLINE | ID: mdl-21745465

ABSTRACT

Alpha-tocopherol has numerous nonenzymatic actions and is a powerful liposoluble antioxidant. The objective of the present study was to evaluate the neuroprotective effects of alpha-tocopherol in rats against oxidative stress caused by pilocarpine-induced seizures. Wistar rats were intraperitoneally treated with 0.9% saline (control group), alpha-tocopherol (200 mg/kg, alpha-tocopherol group), pilocarpine (400 mg/kg, pilocarpine group), or the combination of alpha-tocopherol (200 mg/kg) and pilocarpine (400 mg/kg, i.p.; alpha-tocopherol plus pilocarpine group). After the treatments, all groups were observed for 24 h. The superoxide dismutase (Mn-SOD) and catalase activities, lipid peroxidation and nitrite concentrations were measured using spectrophotometrically methods. To clarify the mechanism of alpha-tocopherol on oxidative stress in pilocarpine model, Western blot analysis of Mn-SOD and catalase in rat striatum were performed. In the pilocarpine group, rats showed a significant increase in lipid peroxidation and nitrite levels. However, there were no alterations on Mn-SOD activity. On the other hand, the catalase activity augmented in pilocarpine group. In the alpha-tocopherol and pilocarpine co-administered rats, antioxidant treatment significantly reduced the lipid peroxidation level and nitrite content and increased the Mn-SOD and catalase activities in rat striatum after seizures. Pilocarpine, alpha-tocopherol plus pilocarpine and alpha-tocopherol groups did not affect of the Mn-SOD and catalase mRNA or protein levels. Our findings strongly support the hypothesis that oxidative stress occurs in striatum during pilocarpine-induced seizures, indicating that brain damage induced by the oxidative process plays a crucial role in seizures pathogenic consequences, which implies that strong protective effect could be achieved using alpha-tocopherol.


Subject(s)
Neostriatum/drug effects , Neostriatum/metabolism , Oxidative Stress/drug effects , Pilocarpine/adverse effects , Seizures/chemically induced , Seizures/metabolism , alpha-Tocopherol/pharmacology , Animals , Behavior, Animal/drug effects , Catalase/metabolism , Lipid Peroxidation/drug effects , Male , Neostriatum/pathology , Nitrites/metabolism , Rats , Rats, Wistar , Seizures/drug therapy , Seizures/pathology , Superoxide Dismutase/metabolism , Time Factors , alpha-Tocopherol/therapeutic use
9.
Arq Neuropsiquiatr ; 68(4): 586-91, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20730314

ABSTRACT

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% 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.


Subject(s)
Acetylcholinesterase/metabolism , Antioxidants/pharmacology , Glutathione Peroxidase/metabolism , Hippocampus/enzymology , Seizures/enzymology , Sodium-Potassium-Exchanging ATPase/metabolism , Thioctic Acid/pharmacology , Animals , Hippocampus/drug effects , Male , Pilocarpine , Rats , Rats, Wistar , Seizures/chemically induced
10.
Arq. neuropsiquiatr ; 68(4): 586-591, Aug. 2010. graf, tab
Article in English | LILACS | ID: lil-555239

ABSTRACT

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.


Subject(s)
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
11.
Brain Res Bull ; 81(4-5): 505-9, 2010 Mar 16.
Article in English | MEDLINE | ID: mdl-19800952

ABSTRACT

Temporal lobe epilepsy is the most common form of epilepsy in humans. Oxidative stress is a mechanism of cell death induced by seizures. Buspirone presents anxyolitic and antidepressant effects due to their ability to stimulate 5-HT(1A) receptor. We studied the buspirone effects on oxidative stress in rat hippocampus after seizures and status epilepticus (SE) induced by pilocarpine. In pilocarpine group there was a significant increase in lipid peroxidation and nitrite levels. However, no alteration was observed in superoxide dismutase and catalase activities. Buspirone pretreatment produces significantly reduction of the lipid peroxidation level (60%) and nitrite content (44%) as well as increased the superoxide dismutase (47%) and catalase (40%) activities in rat hippocampus after seizures, when compared with the pilocarpine group. The intraperitoneal injection of buspirone prior to pilocarpine suppressed the behavioral seizure occurrence. According to our results, the oxidative stress is present during seizures. Buspirone exerted anticonvulsant effects associated with the inhibition of the development of oxidative stress. These results suggest a therapeutic use potential of buspirone in epilepsy treatment.


Subject(s)
Buspirone/pharmacology , Hippocampus/drug effects , Oxidative Stress/drug effects , Seizures/drug therapy , Seizures/physiopathology , Serotonin Receptor Agonists/pharmacology , Animals , Anticonvulsants/administration & dosage , Anticonvulsants/pharmacology , Buspirone/administration & dosage , Catalase/metabolism , Hippocampus/physiopathology , Lipid Peroxidation/drug effects , Male , Nitrites/metabolism , Oxidative Stress/physiology , Pilocarpine , Rats , Rats, Wistar , Seizures/chemically induced , Serotonin Receptor Agonists/administration & dosage , Status Epilepticus/chemically induced , Status Epilepticus/drug therapy , Status Epilepticus/physiopathology , Superoxide Dismutase/metabolism , Time Factors
12.
Brain Res ; 1315: 33-40, 2010 Feb 22.
Article in English | MEDLINE | ID: mdl-20034476

ABSTRACT

Recent researches have shown that antioxidant compounds may have certain neuroprotective effect against the neurotoxicity of seizures at cellular level. Ubiquinone (UQ), an antioxidant compound, exhibits a wide range of therapeutic effects that are attributed to its potent antioxidant capacity. The objective of the present study was to evaluate the neuroprotective effects of UQ in rats, against the observed oxidative stress during seizures induced by pilocarpine. Wistar rats were treated with either 0.9% saline (i.p., control group), UQ (5, 10 or 20 mg/kg, i.p., UQ5, UQ10 and UQ20 groups), pilocarpine (400 mg/kg, i.p., P400 group), or co-administration of pilocarpine with UQ group rats 30 min prior to UQ administration. After the treatments all groups were observed for 24 h. The antioxidant enzymatic activities as well as the hydroperoxide concentrations were measured using spectrophotometric methods and the results were analyzed. In pilocarpine group there was a significant increase in hydroperoxides concentration and glutathione peroxidase activity. However, no alteration was observed in superoxide dismutase and catalase activities. Antioxidant treatment significantly reduced the hydroperoxide content and increased the superoxide dismutase, catalase and glutathione peroxidase activities in rat hippocampus during seizures induced by pilocarpine. Our findings strongly support the hypothesis that oxidative stress in hippocampus occurs during seizures induced by pilocarpine, which indicates that brain damage induced by the oxidative process plays a crucial role in seizures pathogenic consequences. Our result also suggests that ubiquinone can exert significant neuroprotective effects that might be useful in the treatment of neurodegenerative diseases.


Subject(s)
Antioxidants/metabolism , Hippocampus/drug effects , Hydrogen Peroxide/metabolism , Neuroprotective Agents/pharmacology , Seizures/drug therapy , Ubiquinone/pharmacology , Animals , Catalase/metabolism , Dose-Response Relationship, Drug , Glutathione Peroxidase/metabolism , Hippocampus/enzymology , Hippocampus/metabolism , Male , Neuroprotective Agents/administration & dosage , Oxidative Stress/drug effects , Oxidative Stress/physiology , Pilocarpine , Rats , Rats, Wistar , Seizures/chemically induced , Seizures/metabolism , Superoxide Dismutase/metabolism , Time Factors , Ubiquinone/administration & dosage
13.
Pharmacol Biochem Behav ; 95(1): 88-91, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20026167

ABSTRACT

In the present study we investigated the effects of lipoic acid (LA) on delta-aminolevulinic dehydratase (delta-ALA-D) and Na(+), K(+)-ATPase activities in rat brain after seizures induction by pilocarpine. Wistar rats were treated with 0.9% saline (i.p., control group), lipoic acid (10mg/kg, i.p., LA group), pilocarpine (400mg/kg, i.p., pilocarpine group), or the combination of LA (10mg/kg, i.p.) with pilocarpine (400mg/kg, i.p.), 30 min before administration of LA (LA plus pilocarpine group). After the treatments all groups were observed for 1h. The enzyme activities (delta-ALA-D and Na(+), K(+)-ATPase) were measured using spectrophotometric methods, and the results were compared with that obtained from saline and pilocarpine-treated animals. Neuroprotective effects of LA against seizures were evaluated based on those enzyme activities. The pilocarpine group showed a reduction in delta-ALA-D and Na(+), K(+)-ATPase activities after seizures. In turn, LA plus pilocarpine abolished the appearance of seizures and reversed the decreased in delta-ALA-D and Na(+), K(+)-ATPase activities produced by seizures, when compared to the pilocarpine seizing group. The results from the present study demonstrate that preadministration of LA abolished seizure episodes induced by pilocarpine in rat, probably by increasing delta-ALA-D and Na(+), K(+)-ATPase activities in rat brain during seizures.


Subject(s)
Brain/drug effects , Pilocarpine/adverse effects , Porphobilinogen Synthase/metabolism , Seizures/prevention & control , Sodium-Potassium-Exchanging ATPase/metabolism , Thioctic Acid/administration & dosage , Animals , Brain/enzymology , Male , Rats , Rats, Wistar , Seizures/chemically induced
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