RESUMO
BACKGROUND: Patients with ST-segment elevation (STEMI) have totally occluded vessels, while patients with non-ST-segment elevation (NSTEMI) present partial vessel occlusion, which may generate different levels of Reactive Oxygen Species (ROS). Objectives: The aim of this study was to compare the oxidative profile in AMI patients with ST segment elevation and non-STEMI as well as control subjects. METHODS: This study was carried with 46 AMI patients divided into STEMI and NSTEMI. The control group consisted of 40 healthy subjects. Oxidative stress profile was evaluated analyzing carbonyl protein (PCO), lipid peroxidation (TBARS), ischemia-modified albumin (IMA), vitamin C (VIT C), superoxide dismutase (SOD) and catalase (CAT). RESULTS: Serum PCO (p < 0.001), plasma TBARS (p < 0.01), serum IMA (p < 0.0001) levels, erythrocytes CAT (p < 0.001), and SOD activities (p < 0.05) were significantly higher in STEMI patients when compared with the control group (p < 0.001). No difference in the IMA levels and oxidative stress parameters was observed between conditions of AMI. Only plasma VIT C in STEMI patients was significantly lower when compared with NSTEMI patients and control group (p < 0.001). CONCLUSIONS: Results suggest that the oxidative profile generated by STEMI and NSTEMI is similar regardless of the size of arterial occlusion generated by thrombus.
Assuntos
Eletrocardiografia , Infarto do Miocárdio/metabolismo , Ácido Ascórbico/sangue , Catalase/metabolismo , Humanos , Pessoa de Meia-Idade , Oxirredução , Superóxido Dismutase/metabolismoRESUMO
CONTEXT: Syzygium cumini (Myrtaceae) presents antioxidant, anti-inflammatory, hypoglycemic and antibacterial effects; however, the cellular and molecular mechanisms of action in the immune system are not yet completely elucidated. OBJECTIVE: This study evaluates the in vitro effect of gallic acid and aqueous S. cumini leaf extract (ASc) on adenosine deaminase (ADA) and dipeptidyl peptidase IV (DPP-IV) activities, cell viability and oxidative stress parameters in lymphocytes exposed to 2, 2'-azobis-2-amidinopropane dihydrochloride (AAPH). MATERIALS AND METHODS: Lymphocytes were incubated with ASc (100 and 500 µg/ml) and gallic acid (50 and 200 µM) at 37 °C for 30 min followed by incubation with AAPH (1 mM) at 37 °C for 2 h. After the incubation time, the lymphocytes were used for determinations of ADA, DPP-IV and lactate dehydrogenase (LDH) activities, lipid peroxidation, protein thiol (P-SH) group levels and cellular viability by colorimetric methods. RESULTS: (i) HPLC fingerprinting of ASc revealed the presence of catechin, epicatechin, rutin, quercitrin, isoquercitrin, quercetin, kaempferol and chlorogenic, caffeic, gallic and ellagic acids; (ii) for the first time, ASc reduced the AAPH-induced increase in ADA activity, but no effect was observed on DPP-IV activity; (iii) ASc increased P-SH groups and cellular viability and decreased LDH activity, but was not able to reduce the AAPH-induced lipid peroxidation; (iv) gallic acid showed less protective effects than ASc. DISCUSSION AND CONCLUSION: ASc affects the purinergic system and may modulate adenosine levels, indicating that the extract of this plant exhibits immunomodulatory properties. ASc also may potentially prevent the cellular injury induced by oxidative stress, highlighting its cytoprotective effects.
Assuntos
Antioxidantes/farmacologia , Ácido Gálico/farmacologia , Linfócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Syzygium/química , Amidinas/farmacologia , Antioxidantes/isolamento & purificação , Técnicas de Cultura de Células , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Linfócitos/patologia , Extratos Vegetais/isolamento & purificação , Folhas de Planta/químicaRESUMO
ABSTRACT Solanum guaraniticum is a medicinal plant traditionally used to treat gastric and liver diseases. However, there is no documented evidence corroborating its safety. The present study evaluated the potential toxicity of S. guaraniticum leaf extract after acute administration in rats. Single doses of the extract (1.250, 2.500, and 5.000 mg/kg) were administered by gavage, and the rats were then monitored for 48 h and/or 14 days. Mortality, acute signs of toxicity, and general activity in the open field test were assessed as well as hematological and biochemical parameters, enzymatic activity (δ-aminolevulinate dehydratase and acetylcholinesterase), and oxidative stress parameters (lipid peroxidation level, non-protein thiol content, tissue catalase activity, and serum ferrous reducing power). Phytochemical analysis was also performed by HPLC. The results showed that extract administration produced no deaths (LD50 > 5,000 mg/kg), and no significant adverse effects regarding food consumption, body weight gain, gross pathology, or other parameters. However, the open field tests showed a decrease in spontaneous activity (crossing and rearing) mainly at 48 h after treatment. The results suggest that S. guaraniticum extract is not acutely toxic, but causes alterations in central nervous system activity.
RESUMO Solanum guaraniticum é uma planta medicinal tradicionalmente usada para tratar doenças gástricas e hepáticas. Porém, não há evidências documentadas sobre sua segurança. O presente estudo avaliou a toxicidade do extrato das folhas de S. guaraniticum após administração aguda em ratos. Doses únicas do extrato (1.250, 2.500 and 5.000 mg/kg) foram administradas por gavagem e os animais foram monitorados por 48 h ou 14 dias. Mortalidade, sinais de toxicidade aguda e atividade geral, através do teste de campo aberto, foram analisados, assim como parâmetros hematológicos e bioquímicos, atividades enzimáticas (δ-aminolevulinato desidratase e acetilcolinesterase) e parâmetros de estresse oxidativo (nível de peroxidação lipídica, conteúdo de tióis não protéicos, atividade da catalase em tecidos e poder redutor em soro). A análise fitoquímica também foi realizada por HPLC. Os resultados mostraram que a administração do extrato não provoca mortes (LD50>5.000 mg/kg) ou efeitos adversos significativos com relação ao consumo de comida, ganho de peso corporal, análise patológica, entre outros. Entretanto, o teste de campo aberto mostrou uma diminuição na atividade espontânea geral (cruzamentos e levantadas), principalmente em 48 h após o tratamento. Portanto, nossos resultados sugerem que o extrato de S. guaraniticum não é agudamente tóxico, mas causa alterações na atividade do sistema nervoso central.
Assuntos
Ratos , Ratos/fisiologia , Solanum/toxicidade , /classificação , Plantas Medicinais/classificação , Solanaceae/classificaçãoRESUMO
BACKGROUND: The hydrolysis of adenine nucleotide linked to the membrane of the platelets is changed in acute myocardial infarction (AMI) probably due to a greater arterial blockage and cell damage in patients with ST elevation (STEMI) than in those without ST segment elevation (NSTEM). METHODS: This study aimed to compare the extracellular hydrolysis of adenine nucleotides on the platelet surface of STEMI and NSTEMI patients. This study was carried out with 50 patients with AMI (STEMI and NSTEMI). The extracellular hydrolysis of adenine nucleotides and nucleoside adenosine as well as the expression of NTPDase were verified in platelets. RESULTS: The results demonstrated that STEMI patients had significantly higher extracellular hydrolysis of adenine nucleotides (p < 0.001), ADA (adenosine deaminase) activity (p < 0.05), as well as troponin levels (p < 0.0001) when compared to NSTEMI patients. CONCLUSIONS: Findings suggest that the extracellular hydrolysis of adenine nucleotides and increase in the ADA activity are higher in patients with STEMI than in those with NSTEMI probably because there was a blockage in this major arterial with a large area of damaged tissue.
Assuntos
Nucleotídeos de Adenina/sangue , Adenosina/sangue , Plaquetas/metabolismo , Membrana Celular/metabolismo , Infarto do Miocárdio/sangue , Adenosina Desaminase/sangue , Biomarcadores/sangue , Plaquetas/enzimologia , Membrana Celular/enzimologia , Feminino , Humanos , Hidrólise , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/enzimologia , Troponina/sangue , Regulação para CimaRESUMO
BACKGROUND: The effects of the aqueous seed extract of Syzygium cumini (ASc) in a short-term model of diabetes in rats are little explored. The present study was designed to evaluate the effect of the ASc on adenosine deaminase (ADA) activity and on biochemical and histopathological parameters in diabetic rats. METHODS: ASc (100 mg/kg) was administered for 21 days in control and streptozotocin (STZ)-induced (60 mg/kg) diabetic rats. ADA activity, lipoperoxidation (cerebral cortex, kidney, liver and pancreas) and biochemical (serum) and histopathological (pancreas) parameters were evaluated. RESULTS: The main findings in this short-term model of Diabetes mellitus (DM) were that the ASc (i) significantly reverted the increase of ADA activity in serum and kidney; (ii) ameliorated the lipoperoxidation in the cerebral cortex and pancreas of the diabetic group; (iii) demonstrated hypolipidemic and hypoglycemic properties and recovered the liver glycogen; and iv) prevented the HOMA-IR index increase in the diabetic group. Therefore, the ASc can be a positive factor for increasing the availability of substrates with significant protective actions, such as adenosine. Moreover, by maintaining glycogen and HOMA-IR levels, the extract could modulate the hyperglycemic state through the direct peripheral glucose uptake. CONCLUSIONS: Our data revealed that the short-term treatment with ASc has an important protective role under pathophysiological conditions caused by the early stage of DM. These results enhance our understanding of the effect of the ASc on the purinergic system in DM.
Assuntos
Adenosina Desaminase/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Fitoterapia , Extratos Vegetais/farmacologia , Syzygium/química , Inibidores de Adenosina Desaminase , Animais , Glicemia/efeitos dos fármacos , Brasil , Resistência à Insulina , Masculino , Estresse Oxidativo/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Ratos , Ratos Wistar , Sementes/químicaRESUMO
BACKGROUND: Obesity is the hallmark of the metabolic syndrome representing a major global health problem. It is considered a state of chronic inflammation with minimal exploration of salivary biomarkers. Thus, the intent of the present study was to assess the activities of salivary dipeptidyl peptidase IV (DPP-IV), adenosine deaminase (ADA) and lipid peroxidation in obese young and overweight young subjects. METHODS: ADA, DPP-IV activities and lipid peroxidation were investigated in saliva, as well as insulin, glucose, HbA1c, HOMA and anthropometric measurements in 149 young adults, including 54 with normal weight, 27 overweight and 68 obese subjects. RESULTS: Salivary ADA and DPP-IV activities as well as lipid peroxidation were higher in patients with obesity compared to the normal weight group. Correlations between ADA/DPP-IV activities, lipid peroxidation/ADA activity, ADA activity/hip circumference and BMI/weight were observed. CONCLUSIONS: Our results indicate that the increase in the salivary ADA and DPP-IV activities as well as in the lipid peroxidation could be related of the regulation to various aspects of adipose tissue function and inflammatory obesity. It is suggested that these salivary biomarkers may be used as biochemical test in clinical abnormalities present in obesity, in the absence of oral inflammatory diseases.
Assuntos
Adenosina Desaminase/metabolismo , Dipeptidil Peptidase 4/metabolismo , Peroxidação de Lipídeos , Obesidade/metabolismo , Saliva/enzimologia , Feminino , Humanos , Resistência à Insulina , Masculino , Obesidade/enzimologia , Adulto JovemRESUMO
OBJECTIVE: This study aimed to investigate the effect of the leaf extracts of Syzygium jambos and Solanum guaraniticum on the δ-aminolevulinate dehydratase (δ-ALA-D) activity, their antioxidant activity and potential protective action on oxidatively stressed erythrocytes, in order to demonstrate the safety or toxicity of the plant. METHODS: In erythrocyte samples, the effect of both extracts on δ-ALA-D activity, H2O2-induced oxidative stress, and 2,2'azobis (2-amidinopropane) (AAPH)-induced hemolysis was evaluated, as well as some antioxidant mechanisms. RESULTS: Both extracts inhibited δ-ALA-D activity (S. guaraniticum > S. jambos), and an involvement of the zinc ion of the δ-ALA-D structure on the inhibition of enzyme activity was verified. S. jambos leaf extract showed marked efficiency in countering H2O2-induced lipid peroxidation and in maintaining cellular integrity against AAPH-induced hemolysis. Furthermore, S. jambos exhibited greater H2O2 scavenging activity and stronger reduction power than S. guaraniticum. DISCUSSION: Both extracts bear potent antioxidant property as an important beneficial effect. However, the inhibition of δ-ALA-D activity suggests a possible harmful effect of these vegetal preparations and indicates the need for further investigation regarding their toxicological properties. All together, these data represent a significant contribution to the knowledge of these plants, both to the scientific community and to the folk medicine.
Assuntos
Eritrócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Sintase do Porfobilinogênio/metabolismo , Solanum/química , Syzygium/química , Amidinas/farmacologia , Antioxidantes/metabolismo , Eritrócitos/enzimologia , Hemólise/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Oxidantes/farmacologia , OxirreduçãoRESUMO
Syzygium cumini (S. cumini) is a plant known for its antidiabetic properties. The aim of this study was to evaluate the effect of Sc aqueous leaf extract (ASc) on adenosine deaminase (ADA) activity in erythrocytes (RBCs) exposed to high glucose concentrations (30 mM) in vitro. We also investigated the effects of the main phenolic compounds found in ASc (gallic acid, rutin, and chlorogenic acid) and the effects of insulin, caffeine, and dipyridamole, which are substances involved in the adenosine metabolism, on ADA activity in vitro. Blood samples were obtained from healthy volunteers and a suspension of RBCs was used for the determination of ADA activity. The results showed that: (1) the effect of ASc on ADA activity was more significant than the combination of phenolic compounds; (2) insulin, caffeine, or dipyridamole prevented high glucose increase of ADA activity at doses as low as 50 µU/mL, 25 µM, and 1 µM, respectively; (3) the inhibitory effect caused by ASc on erythrocyte ADA activity remained practically the same after the combination of the extract with insulin or caffeine; (4) when RBCs were exposed to ASc plus dipyridamole, this chemical attenuated the effect of ASc on ADA activity, suggesting an antagonism or a competition with ASc by the same site of action. Therefore, ASc was more effective in preventing the increase in ADA activity than phenolic compounds, suggesting that ASc may collaborate to improve endothelial dysfunction, antioxidant, anti-inflammatory, and antithrombotic properties of adenosine by affecting its metabolism. The results of this study help to provide evidence of the empirically supported benefits of the use of S. cumini in diabetes.
Assuntos
Adenosina Desaminase/sangue , Eritrócitos/efeitos dos fármacos , Hiperglicemia/sangue , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Syzygium/química , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Eritrócitos/enzimologia , Humanos , Técnicas In VitroRESUMO
Metabolic syndrome (MetS) leads to changes in enzymatic activities, oxidative and inflammatory parameters. Adenosine deaminase (ADA), dipeptidyl peptidase IV (DPP-IV), butyrylcholinesterase (BuChE) and γ-glutamyltransferase (γ-GT) activities, C-reactive protein (hsCRP) and nitric oxide levels (NOx), as well as oxidative stress markers were analyzed in 39 subjects with MetS and 48 controls. Also, the influence of body mass index (BMI) and anthropometric measurements were evaluated. Disturbances in antioxidant defenses and higher γ-GT and BuChE activities, NOx and hsCRP levels were observed in subjects with MetS. These findings remained associated with MetS after adjustment for BMI, except for hsCRP. ADA was correlated with age, insulin levels and HOMA-IR index in MetS. DPP-IV and total cholesterol (TC), BuChE activity and TC, and VIT C and hsCRP levels also were correlated. The analyzed parameters may reflect the inflammatory state of the MetS, and could contribute to prevention and control of various aspects of this syndrome.
Assuntos
Butirilcolinesterase/metabolismo , Síndrome Metabólica/enzimologia , Síndrome Metabólica/metabolismo , Estresse Oxidativo/imunologia , gama-Glutamiltransferase/metabolismo , Adenosina Desaminase/metabolismo , Biomarcadores/metabolismo , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Colesterol/sangue , Dipeptidil Peptidase 4/metabolismo , Feminino , Humanos , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismoRESUMO
Syzygium jambos and Solanum guaraniticum are both employed in Brazil as medicinal plants, even though their potential toxicity is not well established and they are frequently misused. The aim of this study was investigate the effect of the aqueous leaf extracts of both plants on δ-aminolevulinate dehydratase (δ-ALA-D) and acetylcholinesterase (AChE) activities and the antioxidant action against oxidative damage induced by sodium nitroprusside in rats, using in vitro assays. In addition, the presence of gallic, caffeic and chlorogenic acids, as well as rutin, quercetin and kaempferol as bioactive compounds in the extracts was identified by HPLC and their levels quantified. The antioxidant activities of both extracts were assessed by their capabilities to scavenge nitric oxide and to inhibit lipid peroxidation. Only Syzygium jambos presented thiol-peroxidase-like activity. Although neither extract affected the AChE activity, the aqueous extract of Solanum guaraniticum inhibited brain δ-ALA-D activity, suggesting a possible impairment effect on the central nervous system. Our results showed that both extracts exhibited efficient free radical scavenger activity and are an interesting source of bioactive compounds, justifying their use in folk medicine, although Solanum guaraniticum extract could have neurotoxicity properties and we therefore suggest that its use should be restricted to ensure the health of the population.
Assuntos
Antioxidantes/metabolismo , Encéfalo/efeitos dos fármacos , Solanum/química , Syzygium/química , Acetilcolinesterase/metabolismo , Animais , Encéfalo/metabolismo , Brasil , Peroxidação de Lipídeos/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Plantas Medicinais/química , Sintase do Porfobilinogênio/metabolismo , RatosRESUMO
OBJECTIVES: Metabolic syndrome (MetS) is considered a state of chronic inflammation. This study aimed to ascertain selected parameters of purinergic and cholinergic systems related to glucose metabolism and inflammation, as well as (γ)-glutamyltransferase (GGT) and N-acetyl-b-glucosaminidase (NAG) activities and lipoperoxidation in lymphocytes of patients with MetS. DESIGN AND METHODS: The adenosine deaminase (ADA), dipeptidyl peptidase IV (DPP-IV), acetylcholinesterase (AChE), GGT and NAG activities, as well as thiobarbituric acid reactive substances (TBARS) levels were investigated in lymphocytes of patients with MetS (n=38) and healthy volunteers (n=41). We also evaluated the insulin levels, anthropometric measurements and routine biochemical analyses. RESULTS: ADA (p<0.05), DPP-IV and AChE (p<0.0001) activities were higher in patients with MetS when compared to the control group. Furthermore, we observed correlations between ADA and DPP-IV activities (p=0.0002; r=0.5945), TBARS levels and ADA (p=0.0021; r=0.5172) and DPP-IV activities (p=0.0022; r=0.5010). CONCLUSIONS: Our findings showed that MetS might cause tissue distress that disturbed lymphocytic ADA, DPP-IV and AChE activities in response to inflammatory stimuli. These alterations evidence clinical abnormalities, since these enzymatic systems are able to regulate several aspects of adipose tissue function and inflammatory state of MetS and could be used successfully both for preventing and for halting the progression of MetS.
Assuntos
Peroxidação de Lipídeos , Linfócitos/enzimologia , Síndrome Metabólica/enzimologia , Adulto , Biomarcadores/análise , Estudos de Casos e Controles , Dipeptidil Peptidase 4/metabolismo , Ativação Enzimática , Ensaios Enzimáticos , Feminino , Humanos , Inflamação/enzimologia , Insulina/metabolismo , Masculino , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Fatores de Risco , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , beta-N-Acetil-Galactosaminidase/metabolismo , gama-Glutamiltransferase/metabolismoRESUMO
AIMS: To assess the effect of hypertension on δ-aminolevulinate dehydratase (δ-ALA-D) activity of type 2 diabetic patients (T2DM). METHODS: δ-ALA-D activity and reactivation index, as well as markers of oxidative stress, biochemical and anthropometrics parameters were determined in T2DM (n=23), type 2 diabetic patients with hypertension (T2DM/HT) (n=30) and controls (n=30). RESULTS: T2DM/HT presented a greater inhibition of δ-ALA-D activity, a higher reactivation index (p<0.05) and a greater depletion of plasma protein thiol groups (P-SH) when compared to T2DM. Moreover, δ-ALA-D activity was positively associated with SH groups and negatively associated with serum protein carbonyl (PC) while its reactivation index was negatively associated with SH groups and positively associated with PC. CONCLUSIONS: These results point out that there is a possible interference of hypertension on the mechanism of the δ-ALA-D activity suggesting that this condition aggravated the oxidative stress of diabetes mellitus.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Hipertensão/epidemiologia , Hipertensão/metabolismo , Sintase do Porfobilinogênio/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Carbonilação Proteica , Compostos de Sulfidrila/metabolismoRESUMO
The aim of the present study was to investigate the effects of Syzygium cumini leaf extract (ASc), on Adenosine deaminase (ADA) and Acetylcholinesterase (AChE) activities, and also on oxidative stress parameters in erythrocytes hemolysates (RBCs) and erythrocytes membranes (ghosts) from type 2 diabetics patients (Type 2 DM) under in vitro conditions. Non protein thiol groups (NP-SH), AChE, Catalase (CAT) and Superoxide Dismutase (SOD) activities were measure in RBCs. Further, ADA activity, Thiobarbituric Acid-Reactive Substances (TBARS) levels and protein thiol groups (P-SH) were estimated in ghosts. Also, P-SH and Vitamin C (VIT C) were measure in plasma sample. The results demonstrated that ADA and AChE activities, besides TBARS levels were higher in erythrocytes of Type 2 DM, while SOD activity and NP-SH levels were decreased when compared to control group. ASc, in vitro, reduced ADA and AChE activities and some parameters of oxidative stress. Furthermore, we observed correlations between VIT C and P-SH levels, ADA activity and P-SH levels, as well as NP-SH and TBARS levels in diabetics. The results suggest that ASc in vitro is able to promote the reduction of inflammation and oxidative stress parameters, and act against biochemical changes occurring in Diabetes mellitus (DM).
Assuntos
Antioxidantes/metabolismo , Diabetes Mellitus Tipo 2/enzimologia , Diabetes Mellitus Tipo 2/metabolismo , Eritrócitos/enzimologia , Eritrócitos/metabolismo , Extratos Vegetais/farmacologia , Folhas de Planta/química , Syzygium/química , Acetilcolinesterase/metabolismo , Adenosina Desaminase/metabolismo , Catalase/metabolismo , Células Cultivadas , Eritrócitos/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
OBJECTIVES: To investigate the activity of δ-Aminolevulinate dehydratase (δ-ALA-D) and its possible relationship with oxidative status, lipid profile, body mass index (BMI) in type 2 diabetics (DM2) patients. DESIGN AND METHODS: δ-ALA-D activity and reactivation index, as well as markers of oxidative stress and biochemical and anthropometrics parameters were determined in DM2 patients (n = 63) and controls (n = 63). RESULTS: There was a decreased δ-ALA-D activity and a higher reactivation index (p<0.05) in DM2 patients besides an elevated level of oxidative stress. Disturbances on lipid profile were related to the enzymatic activity and BMI also was correlated with oxidative level in DM2 patients (p<0.05). CONCLUSION: There is an association between oxidative stress, abnormalities on lipid profile, distribution of body fat and δ-ALA-D activity inhibition as well as the enzyme is more oxidized in the DM2 suggesting that it would be a good biomarker for assessing prejudice in chronic metabolic processes.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Lipídeos/sangue , Estresse Oxidativo , Sintase do Porfobilinogênio/metabolismo , Biomarcadores , Índice de Massa Corporal , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/enzimologia , Humanos , Oxirredução , Sintase do Porfobilinogênio/antagonistas & inibidoresRESUMO
BACKGROUND: Bone marrow transplantation (BMT) is often used in the treatment of various diseases. Before BMT, patients are submitted to a conditioning regimen (CR), which consists of the administration of high doses of chemotherapy. The action of many cytostatic drugs involves the overproduction of reactive oxygen species, which together with inadequate antioxidant protection can lead to oxidative stress and this has been implicated in the etiology of various diseases. The objectives of this study were to look for evidence of oxidative stress and also to analyze delta-Aminolevulinato dehydratase (delta-ALA-D) activity as a possible marker of oxidative stress in autologous and allogeneic BMT patients. METHODS: Lipid peroxidation, vitamin C and thiol group levels as well as catalase, superoxide dismutase and delta-ALA-D activity were determined in 37 healthy controls, 13 patients undergoing autologous peripheral blood stem cell transplantation and 24 patients undergoing allogeneic BMT. RESULTS: We found that patients presented signs of oxidative stress before they were submitted to BMT, during CR and up to 20 days after BMT. There was a decrease in enzymatic and non enzymatic antioxidant defenses, in delta-ALA-D activity, and an increase in lipoperoxidation in the blood of both patient groups. CONCLUSION: This study has indicated that autologous and allogeneic BMT are associated with oxidative stress. Moreover, blood delta-ALA-D activity seems to be an additional biomarker of oxidative stress in BMT patients.
Assuntos
Transplante de Medula Óssea , Estresse Oxidativo , Sintase do Porfobilinogênio/sangue , Adulto , Ácido Ascórbico/sangue , Biomarcadores/metabolismo , Catalase/sangue , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Peroxidação de Lipídeos , Masculino , Pessoa de Meia-Idade , Superóxido Dismutase/sangue , Condicionamento Pré-Transplante , Transplante Autólogo , Transplante HomólogoRESUMO
Severe toxicity is associated with cytotoxic drugs used during the conditioning regimen (CR) preceding bone marrow transplantation (BMT). The aim of this study was to evaluate the involvement of oxidative stress and possible use of delta-aminolevulinate dehydratase (delta-ALA-D) activity as a marker of oxidative stress in autologous BMT patients. We have also compared common drugs that are used during CR, namely, melphalan (M-200) and cyclophosphamide-BCNU-etoposide (CBV), in order to determine whether either of them could be less toxic to patients in terms of oxidative stress. The sample consisted of 10 patients admitted for autologous BMT, 5 with M-200 CR and 5 with CBV CR and 10 healthy controls. Lipid peroxidation (estimated as thiobarbituric acid-reactive substances, TBARS), vitamin C, thiol levels, catalase, superoxide dismutase and delta-ALA-D activity were determined before CR, during CR and on days 10 and 20 after BMT. Signs of exacerbated oxidative stress were minimal before CR, except for the CVB group (patients with lymphoma) where an increase in TBARS and a decrease in P-SH were detected. Indices of oxidative stress changed in both groups (CBV and M-200) during CR and up to 20 days after BMT. There was a decrease in enzymatic and non-enzymatic antioxidant defenses and in delta-ALA-D activity and an increase in lipoperoxidation in the blood of both patient groups. In conclusion, CBV and, principally, M-200 caused oxidative stress in patients undergoing autologous BMT and blood delta-ALA-D activity seems to be an additional biomarker of oxidative stress in BMT patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Medula Óssea/efeitos adversos , Melfalan/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Sintase do Porfobilinogênio/sangue , Condicionamento Pré-Transplante/efeitos adversos , Ácido Ascórbico/sangue , Biomarcadores/análise , Carmustina/efeitos adversos , Estudos de Casos e Controles , Ciclofosfamida/efeitos adversos , Etoposídeo/efeitos adversos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio/sangue , Compostos de Sulfidrila/sangue , Transplante AutólogoRESUMO
Successful hematopoietic stem cell transplantation (HSCT), both autologous and allogeneic, requires a rapid and durable engraftment, with neutrophil (>500/microL) and platelet (>20,000/microL) reconstitution. Factors influencing engraftment after autologous or allogeneic HSCT were investigated in 65 patients: 25 autologous peripheral stem cell transplantation (PBSCT) and 40 allogeneic bone marrow transplantation (BMT) patients. The major factor affecting engraftment was the graft source for HSCT. Neutrophil and platelet recovery were more rapid in autologous PBSCT than in allogeneic BMT [neutrophil occurring in median on day 10.00 (09.00/11.00) and 19.00 (16.00/23.00) and platelet on day 11.00 (10.00/13.00) and 21.00 (18.00/25.00), respectively; p < 0.0001]. The type of disease also affected engraftment, where multiple myeloma (MM) and lymphoma showed faster engraftment when compared with leukemia, syndrome myelodysplastic (SMD) and aplastic anemia (AA) and MM presented the best overall survival (OS) in a period of 12 months. Other factors included the drug used in the conditioning regimen (CR), where CBV, melphalan (M-200) and FluCy showed faster engraftment and M-200 presented the best OS, in a period of 12 months and age, where 50-59 years demonstrated faster engraftment. Sex did not influence neutrophil and platelet recovery.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Anemia Aplástica/mortalidade , Anemia Aplástica/terapia , Transplante de Medula Óssea , Feminino , Humanos , Leucemia/mortalidade , Leucemia/terapia , Linfoma/mortalidade , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Transplante de Células-Tronco de Sangue Periférico , Transplante Autólogo , Transplante HomólogoRESUMO
OBJECTIVES: To compare different conditioning regimens (CR), in order to determine whether either of them could be less toxic to allogeneic bone marrow transplantation (BMT) patients in terms of oxidative stress and also analyze delta-ALA-D activity as a possible marker of oxidative stress. DESIGN AND METHODS: Lipid peroxidation, vitamin C, thiol groups levels and catalase, superoxide dismutase and delta-ALA-D activity were determined in 21 healthy controls, 5 patients with fludarabine+cyclophosphamide (FluCy) CR, 12 with busulfan+cyclophosphamide (BuCy) and 4 with cyclophosphamide+total body irradiation (CyTBI). RESULTS: There were a decrease in enzymatic and non enzymatic antioxidants, in delta-ALA-D activity, and in all CRs and an increase in lipid peroxidation more pronounced in CyTBI CR. CONCLUSIONS: All CRs promoted oxidative stress in allogeneic BMT patients, but this was more pronounced with CyTBI and delta-ALA-D activity seemed to be an additional biomarker of oxidative stress in these patients.