RESUMO
Although cardiac muscle hypertrophy has been studied in association with several diseases, its mechanism in patients with emphysema, in particular in relation to oxidative stress and proteolysis, remains unknown. The role of oxidative stress and proteolysis in right and left ventricle hypertrophy was investigated in hamsters with emphysema induced by 2 different doses of papain (20mg/mL, E20 and 40mg/mL, E40). The thickness of the ventricles, total and cardiac weight, lipid peroxidation, carbonyl proteins, total antioxidant capacity (TAC), and proteasomal proteolytic activity were evaluated in the right ventricle (RV) and the left ventricle (LV) of control and emphysema hamsters. RV thickness was increased by 12% in the E20 group and by 29% in the E40 group. Lipid peroxidation measured by chemiluminescence was increased in the E40 group (from 3350.68±392.44URL/g tissue to 4696.63±1076.70URL/g tissue, p<0.05). TAC also increased only in the E40 group. In the LV, chemiluminescence values increased from 4044.77±503.39 to 5517.10±388.27 in the E20 group and to 8169.14±1748.77URL/g tissue in the E40 group (p<0.05, both). TAC significantly increased in the E20 and E40 groups. No differences were detected in substances reactive to thiobarbituric acid or carbonyl proteins when comparing ventricles or doses. Chymotrypsin-like proteolytic activity significantly decreased in both groups and ventricles. Emphysema can induce right and left ventricle lipid peroxidation and result in antioxidant mobilization. These data together support the idea that cardiac hypertrophy in response to emphysema is mediated in part by proteolytic pathways with involvement of reactive species.
RESUMO
A Dietilnitrosamina (DEN), uma substância reconhecidamente hepatotóxica e carcinogênica, foiutilizada na indução da necrose hepática centrolobular em ratos isogênicos Lewis divididos em 5 grupos de 5 animais. O objetivo deste estudo foi avaliar o efeito quimiopreventivo da epigalocatequina-3-galato (EGCG), de Camellia sinensis (chá verde) no tratamento da hepatotoxicidade celular induzida pela DEN. Foi mensurada a concentração sérica da alanina aminotransferase (ALT) e aspartato aminotransferase(AST) dos diferentes grupos experimentais. No ensaio bioquímico para AST e ALT, houve diferença significativa entre os valores médios do grupo controle (163±70,32) comparado ao grupo DEN (1631±1039,44), sugerindo que a DEN influencia na função hepática. Entretanto, não houve diferença significativa entre o grupo DEN e o tratado com epigalocatequina. A lactato desidrogenase (LDH) éconsiderada um marcador bioquímico comum para avaliação da progressão tumoral, e em relação ao LDH, as amostras não apresentaram diferenças significativas entre o grupo DEN (1385,5±43,13) e DEN + EGCG 150mg ou DEN + EGCG 200mg 1537,5±1010,45). Neste trabalho foi demonstrado que a epigalocatequina nas concentrações de 150 e 200 mg/Kg não induziram alterações hepáticas e também não foi possível verificar nenhuma quimioproteção pela EGCG em animais inicialmente tratados comDEN durante 24 horas. Sendo assim, novos experimentos com diferentes concentrações de EGCG sãonecessários para comprovar seu possível efeito quimioprotetor.
Diethylnitrosamine (DEN), a known hepatotoxic and carcinogenic substance, was used in the induction of centrilobular hepatic necrosis in isogenic Lewis rats divided into 5 groups with 5 animals. The aim of this study was to evaluate the chemopreventive effect of epigallocatechin-3-gallate (EGCG)from Camellia sinensis (green tea) in the treatment of cellular hepatotoxicity induced by DEN. It was measured the serum concentration of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of the different experimental groups. In the biochemistry assay for AST and ALT, there was significant difference between median values of control group (163±70.32) compared to DEN group(1631±1039.44), suggesting that DEN influences on hepatic function. However, there was no significant difference between DEN group to that treated with epigallocatechin. Lactate dehydrogenase (LDH) is considered a common biochemical marker for evaluation of tumor progression, and regarding LDH,the samples presented no significant differences between the DEN group (1385.5±43.13) and DEN + EGCG 150mg or DEN + EGCG 200mg (1537.5± 1010.45). In this work it was demonstrated that epigallocatechin concentrations of 150 and 200 mg/kg did not induce liver alterations and though was not verified any chemoprotective effect by EGCG in animals initially treated with DEN for 24 hours. Moreover, new experiments with different concentrations of EGCG are needed to verify its possiblechemoprotector effect.
Assuntos
Animais , Ratos , Dietilnitrosamina , L-Lactato Desidrogenase , Ratos Endogâmicos LewRESUMO
BACKGROUND: Peripheral skeletal muscle is altered in patients suffering from emphysema and chronic obstructive pulmonary disease (COPD). Oxidative stress have been demonstrated to participate on skeletal muscle loss of several states, including disuse atrophy, mechanical ventilation, and chronic diseases. No evidences have demonstrated the occurance in a severity manner. METHODS: We evaluated body weight, muscle loss, oxidative stress, and chymotrypsin-like proteolytic activity in the gastrocnemius muscle of emphysemic hamsters. The experimental animals had 2 different severities of lung damage from experimental emphysema induced by 20 mg/mL (E20) and 40 mg/mL (E40) papain. RESULTS: The severity of emphysema increased significantly in E20 (60.52 ± 2.8, p < 0.05) and E40 (52.27 ± 4.7; crossed the alveolar intercepts) groups. As compared to the control group, there was a reduction on body (171.6 ± 15.9 g) and muscle weight (251.87 ± 24.87 mg) in the E20 group (157.5 ± 10.3 mg and 230.12 ± 23.52 mg, for body and muscle weight, respectively), which was accentuated in the E40 group (137.4 ± 7.2 g and 197.87 ± 10.49 mg, for body and muscle weight, respectively). Additionally, the thiobarbituric acid reactive substances (TBARS), tert-butyl hydroperoxide-initiated chemiluminescence (CL), carbonylated proteins, and chymotrypsin-like proteolytic activity were elevated in the E40 group as compared to the E20 group (p < 0.05 for all comparisons). The severity of emphysema significantly correlated with the progressive increase in CL (r = -0.95), TBARS (r = -0.98), carbonyl proteins (r = -0.99), and chymotrypsin-like proteolytic activity (r = -0.90). Furthermore, augmentation of proteolytic activity correlated significantly with CL (r = 0.97), TBARS (r = 0.96), and carbonyl proteins (r = 0.91). CONCLUSIONS: Taken together, the results of the present study suggest that muscle atrophy observed in this model of emphysema is mediated by increased muscle chymotrypsin-like activity, with possible involvement of oxidative stress in a severity-dependent manner.
Assuntos
Quimotripsina/metabolismo , Músculo Esquelético/enzimologia , Atrofia Muscular/etiologia , Estresse Oxidativo , Enfisema Pulmonar/complicações , Animais , Peso Corporal , Cricetinae , Modelos Animais de Doenças , Pulmão/patologia , Masculino , Mesocricetus , Músculo Esquelético/patologia , Atrofia Muscular/enzimologia , Atrofia Muscular/patologia , Tamanho do Órgão , Papaína , Carbonilação Proteica , Enfisema Pulmonar/induzido quimicamente , Enfisema Pulmonar/enzimologia , Enfisema Pulmonar/patologia , Índice de Gravidade de Doença , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , terc-Butil Hidroperóxido/metabolismoRESUMO
Anemia in patients with uremia undergoing hemodialysis (HD) is a complex process that is dependent on erythropoiesis associated with erythropoietin and iron availability. Published information about an extra erythrocytic factor in the data concerning HD and the underlying mechanism by which anemia occurs remain unclear. The aim of this study was to investigate the superoxide anion generation by polymorphonuclear neutrophils and red blood cell (RBC) lipid peroxidizability as well as the possible association between these parameters and anemia in patients undergoing HD. Blood was collected from 15 volunteers prior to and following HD, and hematological data showed significant anemia at both time points. RBC lipid peroxidizability and neutrophil anion superoxide production, as evaluated by kinetics analysis, revealed increased initial and maximal velocity before and after HD. Plasma malondialdehyde (MDA) and antioxidant levels in the patient group were higher than those in the control group. RBC superoxide dismutase and catalase activities did not differ between groups. There was a significant correlation between increased RBC lipid peroxidizability and superoxide anion production and anemia in patients undergoing HD. The individual variation in plasma MDA was accompanied by superoxide anion production. The RBC lipid peroxidizability, mediated by neutrophil-generated superoxide anions, seems to be a plausible mechanism for explaining, in part, the extraerythrocytic damage that leads to anemia in patients on HD.
RESUMO
Neste trabalho foi obtido soro anti-receptor de linfócitos de carneiro (E) por imunizaçäo de carneiro com eritrócitos autólogos sensibilizados com receptores solubilizados de membranas de linfócitos humanos. A análise desse soro anti-receptor solúvel (anti-Rs) demonstrou a capacidade de inibir a formaçäo da rosácea, de identificar linfócitos T por imunofluorescência indireta, de aglutinar complexo E sensibilizado com receptor solúvel, confirmando os dados da literatura. Considerando que esse soro anti-Rs interage com moléculas de peso molecular aproximado de 58 Kd (Rs1) e acima de 150 Kd (Rs2), foi analisado o efeito bloqueador desse soro anti-Rs na interaçäo de Rs1 e Rs2 a E. Adicionalmente IgG anti-Rs foi purificada através de cromatografia de afinidade utilizando coluna de Sepharose Proteína A e analisada em cultura de linfócitos. Essa IgG anti-Rs purificada, nas concentraçöes de 60 e 120 µg induziu resposta proliferativa de linfócitos humanos normais "in vitro"