RESUMEN

PURPOSE: This study aimed to evaluate markers of cardiac damage (total CK, CKMB and CRP), inflammatory markers (free iron, homocysteine and TNF-α) as well as lipidogram in breast cancer patients undergoing acute cycles of doxorubicin (DOX), paclitaxel (PTX) or trastuzumab (TZ) and to verify if there is an association between these markers and the toxicity of the chemotherapeutic treatment. Methods: Included in the study were 120 breast cancer patients and 50 healthy controls. All analyzes were performed on automated systems. For the statistical analysis, each group was compared with the controls according to their normality by Student's t-test and Mann-Whitney test. Results: Our results showed that DOX treatment led to increased hsCRP (4.80 ± 1.23 mg/dL, p = 0.0005), triglycerides (187.6 ± 25.06, p = 0.0231), TNF-α (42.31 ± 17.96 pg/mL, p = 0.01) and Fe levels (138.8 ± 18.6 µg/dL, p = 0.0193). In the meantime, PTX induced changes in CK-MB (8.78 ± 4.2 U/L, p = 0.0361), hsCRP (7.12 ± 1.87 mg/dL, p = 0.0006), cholesterol (201.7 ± 19.54, p = 0.05), triglycerides (201.7 ± 19.54, p = 0.0277), TNF-α (38.27 ± 9.12 pg/mL, p = 0.023), homocysteine (10.95 ± 0, 86 µmol/L, p = 0.005), and free iron (113 ± 18 6 µg/dL, p = 0.045) while TZ augmented CK-MB (6.9 ± 1.97 U/L, p < 0.00), hsPCR (3.12 ± 0.68 mg/dL, p = 0.095), cholesterol (218.3 ± 16.79, p = 0.0317), triglycerides (218.3 ± 16.79, p = 0.0127), TNF-α (89.6 ± 12.11, p = 0.032), homocysteine (9.95 ± 1.15 µmol/L, p = 0.0396), free iron (120.5 ± 4.64 µg/dl, p = 0.0058) as well. Conclusions: Our data demonstrated the existence of a proinflammatory net triggered by breast cancer chemotherapy that could increase cardiomyocytes permeability and allow the leakage of circulating proteins as CK-MB and induce the production of hsCRP.

Asunto(s)

Antineoplásicos/efectos adversos , Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Cardiopatías/inducido químicamente , Mediadores de Inflamación/metabolismo , Adulto , Anciano , Antineoplásicos/uso terapéutico , Biomarcadores , Doxorrubicina/efectos adversos , Doxorrubicina/farmacología , Femenino , Humanos , Persona de Mediana Edad , Paclitaxel/efectos adversos , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Trastuzumab/efectos adversos , Trastuzumab/farmacología

RESUMEN

PURPOSE: Although paclitaxel-based chemotherapy is widely used for treating breast cancer, paclitaxel therapy has been associated with several adverse effects. Such adverse effects have primarily been associated with long-term regimens, but some acute effects are being increasingly reported in the literature. In this context, the present study analyzed the systemic proteomic profiles of women diagnosed with breast cancer at the first cycle of short paclitaxel infusion (n = 30). Proteomic profiles thus obtained were compared with those of breast cancer patients without chemotherapy (n = 50), as well as with those of healthy controls (n = 40). METHODS: Plasma samples were evaluated by label-free LC-MS to obtain systemic proteomic profiles. Putative dysregulated pathways were identified and validated by in silico analysis of proteomic profiles. RESULTS: Our results identified 188 proteins that were differentially expressed in patients who received a single short paclitaxel infusion when compared to patients who did not receive the infusion. Gene ontology analysis indicated that the cholesterol pathway may be dysregulated by paclitaxel in these patients. Validation analysis showed that paclitaxel treatment significantly reduced plasma high-density lipoprotein levels and increased plasma hydroperoxide levels when compared to breast cancer patients without chemotherapy. Furthermore, augmented C-reactive protein and creatine kinase fraction MB were found to be significantly higher in paclitaxel-treated patients in comparison with healthy controls. CONCLUSIONS: Taken together, these data suggest that a single dose of short paclitaxel infusion is sufficient to trigger significant alterations in lipid metabolism, which puts breast cancer patients at risk for increased incidence of cardiovascular disease.

Asunto(s)

Antineoplásicos Fitogénicos/uso terapéutico , Biomarcadores/sangre , Neoplasias de la Mama/tratamiento farmacológico , Metabolismo de los Lípidos/fisiología , Paclitaxel/uso terapéutico , Enfermedad Aguda , Neoplasias de la Mama/patología , Femenino , Humanos , Paclitaxel/administración & dosificación , Paclitaxel/farmacología

RESUMEN

The aims of the present study were to evaluate biomarkers of oxidative and nitrosative stress in systemic lupus erythematosus (SLE) patients, in particular products of DNA/RNA oxidative damage and their correlation with disease activity. This study included 188 controls and 203 patients; 153 with inactive SLE (SLEDAI < 6) and 50 with active SLE (SLEDAI ≥ 6) without renal impairment. Oxidative stress was assessed by tert-butyl hydroperoxide-initiated by chemiluminescence, advanced oxidation protein products (AOPP), total radical-trapping antioxidant parameter (TRAP), nitric oxide metabolites (NOx), and DNA/RNA oxidation products. Patients with SLE showed increased oxidative stress, as demonstrated by the augmentation of lipid hydroperoxides ( p < 0.0001) and AOPP ( p < 0.001) and reduced total antioxidant capacity ( p < 0.0001), without differences between patients with active disease and in remission. NOx levels and DNA/RNA oxidation products were inversely and independently associated with disease activity ( p < 0.0001 and p = 0.021, respectively), regardless of BMI and prednisone use. The linear regression analysis showed that about 5% of the SLEDAI score can be explained by the levels of DNA/RNA oxidation products ( r2:0.051; p = 0.002) and about 9% of this score by the levels of NOx ( r2:0.091; p < 0.0001). This study provides evidence for an inverse association between serum NOx levels and DNA/RNA oxidation products and SLE disease activity, suggesting that oxidative/nitrosative stress markers may be useful in evaluating SLE disease activity and progression of the disease.

Asunto(s)

Lupus Eritematoso Sistémico/fisiopatología , Óxido Nítrico/metabolismo , Estrés Nitrosativo/fisiología , Estrés Oxidativo/fisiología , Adulto , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Estudios de Casos y Controles , ADN/metabolismo , Progresión de la Enfermedad , Femenino , Glucocorticoides/uso terapéutico , Humanos , Modelos Lineales , Lupus Eritematoso Sistémico/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Prednisona , ARN/metabolismo , Índice de Severidad de la Enfermedad

RESUMEN

In this paper, we investigated the oxidative profile of breast tumors in comparison with their normal adjacent breast tissue. Our study indicates that breast tumors present enhanced oxidative/nitrosative stress, with concomitant augmented antioxidant capacity when compared to the adjacent normal breast. These data indicate that breast cancers may be responsible for the induction of a prooxidant environment in the mammary gland, in association with enhanced TNF-α and nitric oxide.

Asunto(s)

Neoplasias de la Mama/patología , Mama/patología , Glándulas Mamarias Humanas/patología , Estrés Oxidativo , Adulto , Anciano , Área Bajo la Curva , Mama/metabolismo , Neoplasias de la Mama/metabolismo , Cromatografía Líquida de Alta Presión , Femenino , Homocisteína/análisis , Humanos , Peroxidación de Lípido , Malondialdehído/análisis , Glándulas Mamarias Humanas/metabolismo , Persona de Mediana Edad , Óxido Nítrico/análisis , Carbonilación Proteica , Curva ROC , Factor de Necrosis Tumoral alfa/análisis

RESUMEN

Trastuzumab is an immunotargeting therapeutic against breast tumors with amplification of the human epithelial growth factor receptor 2 (HER2). HER2 patients naturally exhibit disruption in the pro-oxidant inflammatory profiling; however, the impact of trastuzumab-based chemotherapy in modulating this process is still unknown. Here we determined the systemic pro-inflammatory profile of women diagnosed with HER2-amplified tumors, undergoing trastuzumab-based chemotherapy (TZ), and compared the results with that of healthy controls (CTR) and untreated patients with HER2-amplified breast cancer (CA). The plasmatic inflammatory profile was assessed by evaluating pro-oxidant parameters such as lipid peroxidation, total antioxidant capacity (TRAP), levels of advanced oxidation protein products (AOPPs), nitric oxide (NO), C-reactive protein (CRP), and total thiol content. Markers of cardiac damage were also assessed. Our findings showed increased NO levels in TZ than that in either CA or CTR groups. Furthermore, TZ augmented TRAP and reduced total thiol than that of the CA group. Our data also revealed that AOPP levels were significantly higher in the TZ than the CA group. AOPP and the MB fraction of creatine-kinase (CKMB) levels were positively correlated in TZ patients. These findings suggest that trastuzumab-associated chemotherapy can modulate the pro-inflammatory markers of HER2-positive breast cancer patients to the levels found in healthy controls.

Asunto(s)

Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma Ductal/tratamiento farmacológico , Quimioterapia , Trastuzumab/administración & dosificación , Adulto , Anciano , Antineoplásicos/efectos adversos , Proteína C-Reactiva/metabolismo , Femenino , Homeostasis/efectos de los fármacos , Humanos , Mediadores de Inflamación/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Persona de Mediana Edad , Terapia Molecular Dirigida , Estadificación de Neoplasias , Óxido Nítrico/metabolismo , Oxidación-Reducción/efectos de los fármacos , Receptor ErbB-2/metabolismo , Compuestos de Sulfhidrilo/metabolismo , Trastuzumab/efectos adversos

RESUMEN

This study evaluated the association of tumor necrosis factor beta (TNF-ß) NcoI polymorphism with the presence of multiple sclerosis (MS), disability, and HLA-DRB1 alleles in 208 Brazilian MS patients. As controls, 147 healthy individuals were included. The disability was evaluated at baseline and 5-year follow-up using the Expanded Disability Status Scale (EDSS). The TNF-ß genotypes were determined using PCR and restriction fragment length polymorphism and serum TNF-α level was determined using enzyme-linked immunosorbent assay. Among the MS patients, 166 (79.8 %) were white, 39 (18.7 %) were brown, and three (1.4 %) were Asian descents (those were excluded from the further analysis). Among the 205 MS patients, 149 (72.6 %) presented remitting-relapsing MS. The baseline and 5-year follow-up EDSS ranged from 0.0 to 3.0 and from 1.0 to 5.7, respectively. The TNFB2/B2 genotype was associated with the presence of MS among the white patients (p = 0.0443). Brown patients presented higher disability (p = 0.0234) and higher TNF-α levels (p = 0.0463) than white patients. White and brown patients carrying TNFB2/B2 genotype exhibited higher TNF-α levels (p = 0.0354 and p = 0.0309, respectively) than those with other geotypes. Association between TNF-ß NcoI genotypes and HLA-DRB1 alleles was not observed among the MS patients (p > 0.05). Taken together, TNFB2 allele was associated with the presence of MS independently of HLA-DRB1 in white patients and the TNFB2/B2 genotype was associated with increased TNF-α levels in white and brown patients, which could be an important genetic factor candidate for the susceptibility and pathogenesis of MS.

Asunto(s)

Cadenas HLA-DRB1/genética , Linfotoxina-alfa/genética , Esclerosis Múltiple/genética , Polimorfismo de Longitud del Fragmento de Restricción , Adulto , Brasil , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/etnología , Factor de Necrosis Tumoral alfa/sangre , Población Blanca

RESUMEN

OBJECTIVES: To determine whether disease activity verified by laboratorial parameters is associated with a higher frequency of hypertension in patients with systemic lupus erythematosus (SLE) without renal impairment and to investigate factors that could influence this hypertension. METHOD: This study included 102 controls, 70 patients with inactive SLE, and 53 patients with active SLE without renal impairment. We evaluated T helper type 1 (Th1)/Th2 lineage cytokines, nitric oxide (NO), insulin resistance (IR), and oxidative stress. RESULTS: Patients with active SLE had a higher probability of developing hypertension compared to controls [odds ratio (OR) 3.833, 95% confidence interval (CI) 1.806-8.137, p < 0.0003] and patients with inactive SLE (OR 2.215, 95% CI 1.032-4.752, p = 0.0394). Active SLE patients had a higher interleukin (IL)-12/IL-4 ratio (p < 0.05) than both controls and inactive SLE patients. Protein oxidation was significantly higher in patients with active SLE than in the control group and in patients with inactive SLE (p < 0.01 and p < 0.05, respectively). Multivariate analysis revealed an association between the presence of hypertension and he levels of glucose (p = 0.0276), insulin (p = 0.0498), hydroperoxides (p = 0.0221), IFN-γ (p = 0.0494), IL-17 (p = 0.0272), IL-12/IL-10 (p = 0.0373), IFN-γ/IL-10 (p = 0.0142), IFN-γ/IL-4 (p = 0.0320), and adiponectin (p = 0.0433). CONCLUSIONS: Patients with active SLE without renal impairment had an increased frequency of high blood pressure (43.4%) compared with patients with inactive SLE (25.7%) and controls (16.7%). Hypertension was associated with serologically active disease and was influenced by an increased Th1/Th2 ratio and oxidative stress.

Asunto(s)

Hipertensión/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Estrés Oxidativo/fisiología , Células TH1/metabolismo , Células Th2/metabolismo , Adulto , Glucemia/metabolismo , Citocinas/sangre , Femenino , Humanos , Hipertensión/inmunología , Hipertensión/metabolismo , Insulina/sangre , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/metabolismo , Masculino , Persona de Mediana Edad , Células TH1/inmunología , Células Th2/inmunología

RESUMEN

OBJECTIVE: The aim of the present study was to assess oxidative stress and iron metabolism in systemic lupus erythematosus (SLE) patients with and without insulin resistance (IR). METHOD: This study included 236 subjects (125 controls and 111 SLE patients). Patients with SLE were divided in two groups: with (n = 72) or without (n = 39) IR. RESULTS: SLE patients with IR showed higher advanced oxidation protein product (AOPP) levels (p = 0.030) and gamma-glutamyltransferase (GGT) levels (p = 0.001) and lower sulfhydryl groups of proteins (p = 0.0002) and total radical-trapping antioxidant parameter (TRAP) corrected by uric acid (UA) levels (p = 0.04) when compared to SLE patients without IR. However, SLE patients with IR presented lower serum 8-isoprostane (p = 0.05) and carbonyl protein levels (p = 0.04) when compared to SLE patients without IR. Serum ferritin levels were significantly higher in SLE patients (p = 0.0006) than in controls, and SLE patients with IR presented higher serum ferritin levels (p = 0.01) than SLE patients without IR. Patients with SLE showed that IR was inversely correlated to TRAP/UA (r = -0.2724, p = 0.0008) and serum ferritin was positively correlated to AOPP (r = 0.2870, p = 0.004). CONCLUSIONS: This study found that oxidative stress was higher in the group of SLE patients with IR, and increased ferritin, whether caused by the inflammatory process per se or hyperinsulinaemia, can favour the redox process. In addition, the preset data reinforce the need to measure oxidative stress with several methodologies with different assumptions.

Asunto(s)

Ferritinas/metabolismo , Resistencia a la Insulina/fisiología , Lupus Eritematoso Sistémico/metabolismo , Lupus Eritematoso Sistémico/fisiopatología , Estrés Oxidativo/fisiología , Adulto , Factores de Edad , Antropometría , Biomarcadores/metabolismo , Estudios de Casos y Controles , Dinoprost/análogos & derivados , Dinoprost/metabolismo , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales , Estadísticas no Paramétricas , gamma-Glutamiltransferasa/metabolismo

RESUMEN

Recent works have shown a dual side of estrogens, and research on the relationship between oxidative stress and menopausal status remains unclear and has produced controversial results. In this work, we aimed to evaluate by sensitive methods the oxidant and antioxidant changes that develop after natural menopause. Thirty premenopausal and 28 naturally postmenopausal women volunteered for this study. Blood was collected and plasma used. 17-OH estradiol levels in plasma were estimated. Plasma levels of advanced oxidation protein products (AOPP), lipid peroxidation products (such as hydroperoxides and malondialdehyde (MDA)), and nitrites were measured, and total radical antioxidant parameter testing was performed to determine the oxidant and antioxidant profiles, respectively. Estrogen levels were significantly increased (p < 0.02) in premenopausal women (54.28 ± 9.34 pg/mL) as compared with postmenopausal women (18.10 ± 1.49 pg/mL). Postmenopausal women had lower levels of lipid hydroperoxide oxidation (p < 0.0001), lipid hydroperoxide levels evaluated by the area under the curve (AUC; 1,366,000 ± 179,400 AUC; p < 0.01), and hydroperoxides as measured by the ferrous oxidation-xylenol orange method (31.48 ± 2.7 µM; p < 0.0001). The MDA levels did not differ between pre- and postmenopausal women whether measured by thiobarbituric acid-reactive substances or high-performance liquid chromatography assays. No differences in AOPP and nitrite levels were observed between pre- and postmenopausal women. Postmenopausal women also exhibited a higher total radical antioxidant level (0.89 ± 0.08 µM Trolox; p < 0.0001). Postmenopausal women demonstrated lower levels of oxidative damage and a higher antioxidant capacity than premenopausal women.

Asunto(s)

Productos Avanzados de Oxidación de Proteínas/sangre , Antioxidantes/metabolismo , Oxidantes/sangre , Estrés Oxidativo/fisiología , Posmenopausia/sangre , Adulto , Cromatografía Líquida de Alta Presión , Femenino , Estudios de Seguimiento , Humanos , Peróxido de Hidrógeno/sangre , Peroxidación de Lípido , Malondialdehído/sangre , Persona de Mediana Edad , Estudios Retrospectivos

RESUMEN

Breast cancer consists in a chronic inflammatory disease with multiple biological and clinical behaviors. Based on high throughput technologies data, this disease is currently classified according to the molecular expression of estrogen (ER), progesterone (PR) and human epidermal growth factor (HER-2) receptors. In this study, we defined the inflammatory profile of the main molecular subtypes of breast cancer patients: luminal (ER and PR positive, HER-2 negative), HER-2 enriched (HER-2 positive) and triple negative (ER, PR and HER-2 negative). Cytokines panel was assessed by measurement of TNF-α, TGF-ß, IL-1, IL-10 and IL-12 plasmatic levels. Oxidative profile was assessed by determination of lipid peroxidation, total antioxidant capacity of plasma, malondialdehyde levels, carbonyl content and nitric oxide (NO). Clinical data were correlated with inflammatory findings. Our findings demonstrated that patients bearing the luminal subtype displayed high TNF-α, TGF-ß and enhanced oxidative stress levels associated with reduced IL-12. HER-2-enriched group exhibited higher levels of TNF-α, IL-12 and TGF-ß associated with enhanced oxidative stress. Triple-negative subtype exhibited the most aggressive profile of disease behavior, with reduction in both TNF-α and TGF-ß, with high levels of lipid peroxidation and NO. The clinical importance of our findings lies in the fact that the inflammatory status varies in distinct ways due to molecular subtype of breast cancer, opening potential therapeutic targets to future therapies.

Asunto(s)

Neoplasias de la Mama/patología , Inflamación/patología , Adulto , Antineoplásicos/uso terapéutico , Antioxidantes/análisis , Neoplasias de la Mama/sangre , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/sangre , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/inmunología , Citocinas/sangre , Doxorrubicina/uso terapéutico , Femenino , Humanos , Inflamación/sangre , Inflamación/tratamiento farmacológico , Peroxidación de Lípido , Malondialdehído/sangre , Persona de Mediana Edad , Invasividad Neoplásica , Óxido Nítrico/sangre , Estrés Oxidativo , Paclitaxel/uso terapéutico , Pronóstico , Receptor ErbB-2/análisis , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Índice de Severidad de la Enfermedad , Resultado del Tratamiento

RESUMEN

Several adverse effects of chemotherapy treatments have been described, and most of these effects are associated with direct interactions between blood cells and indirect effects generated during the oxidative metabolism of antineoplastic drugs. In this study we evaluated the oxidative systemic status and hematological profiles of breast cancer patients with advanced ductal infiltrative carcinoma treated with doxorubicin (DOX) or paclitaxel (PTX) within 1 h after chemotherapy. Blood analyses included evaluation of hemogram, pro-oxidative markers, and antioxidant status. The results showed that advanced breast cancer diseased (AD) patients without previous chemotherapy presented anemia and high oxidative stress status characterized by elevated levels of lipid peroxidation and nitric oxide, and reduced catalase activity when compared with controls. DOX-treated patients exhibited increased anemia and reduced antioxidant status, which was revealed by decreases in reduced glutathione levels and the total antioxidant capacity of plasma; however, these changes did not lead to further increases in lipid peroxidation or carbonyl proteins when compared with the AD group. PTX-treated patients also showed increased anemia, lactate dehydrogenase leakage, and enhanced lipid peroxidation. These data reveal for the first time that patients subjected to chemotherapy with DOX or PTX present immediate systemic oxidative stress and red blood cell oxidative injury with anemia development. These findings provide a new perspective on the systemic redox state of AD and patients subjected to chemotherapy regarding oxidative stress enhancement and its possible involvement in the aggravation of chronic anemia.

Asunto(s)

Neoplasias de la Mama/sangre , Carcinoma Ductal de Mama/sangre , Estrés Oxidativo , Adulto , Anciano , Antioxidantes/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/patología , Catalasa/metabolismo , Eritrocitos/enzimología , Eritrocitos/metabolismo , Femenino , Glutatión/metabolismo , Humanos , Peroxidación de Lípido , Persona de Mediana Edad , Estadificación de Neoplasias , Nitritos/metabolismo , Carbonilación Proteica , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo

RESUMEN

Antineoplastic chemotherapy still consists in the major first-line therapeutics against cancer. Several reports have described the immunomodulatory effects of these drugs based on in vitro treatment, but no previous data are known about these effects in patients and its association with immunological-mediated toxicity. In this study, we first characterize the immunological profile of advanced breast cancer patients treated with doxorubicin and paclitaxel protocols, immediately after chemotherapy infusion. Our findings included an immediate plasmatic reduction in IL-1, IL-10, and TNF-α levels in doxorubicin-treated patients, as well as high levels of IL-10 in paclitaxel patients. Further, it was demonstrated that both drugs led to leukocytes oxidative burst impairment. In vitro analysis was performed exposing healthy blood to both chemotherapics in the same concentration and time of exposition of patients, resulting in low IL-10 and high IL-1ß in doxorubicin exposition, as low TNF-α and high IL-1 in paclitaxel treatment. Nitric oxide levels were not altered in both in vivo and in vitro treatments. In conclusion, our data revealed for the first time that the immediate effects of chemotherapy could be mediated by cytokines signaling in patients and that the results observed in patients could be a resultant of host immune cells activation.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma/tratamiento farmacológico , Doxorrubicina/administración & dosificación , Paclitaxel/administración & dosificación , Adulto , Anciano , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Carcinoma/diagnóstico , Carcinoma/inmunología , Carcinoma/patología , Citocinas/sangre , Doxorrubicina/efectos adversos , Femenino , Humanos , Inmunomodulación , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Paclitaxel/efectos adversos

RESUMEN

Breast cancer is the malignant neoplasia with the highest incidence in women worldwide. Chronic oxidative stress and inflammation have been indicated as major mediators during carcinogenesis and cancer progression. Human studies have not considered the complexity of tumor biology during the stages of cancer advance, limiting their clinical application. The purpose of this study was to characterize systemic oxidative stress and immune response parameters in early (ED; TNM I and II) and advanced disease (AD; TNM III and IV) of patients diagnosed with infiltrative ductal carcinoma breast cancer. Oxidative stress parameters were evaluated by plasmatic lipoperoxidation, carbonyl content, thiobarbituric reactive substances (TBARS), nitric oxide levels (NO), total radical antioxidant parameter (TRAP), superoxide dismutase, and catalase activities and GSH levels. Immune evaluation was determined by TNF-α, IL-1ß, IL-12, and IL-10 levels and leukocytes oxidative burst evaluation by chemiluminescence. Tissue damage analysis included heart (total CK and CKMB), liver (AST, ALT, GGT), and renal (creatinine, urea, and uric acid) plasmatic markers. C-reactive protein (CRP) and iron metabolism were also evaluated. Analysis of the results verified different oxidative stress statuses occur at distinct cancer stages. ED was characterized by reduction in catalase, 8-isoprostanes, and GSH levels, with enhanced lipid peroxidation and TBARS levels. AD exhibited more pronounced oxidative status, with reduction in catalase activity and TRAP, intense lipid peroxidation and high levels of NO, TBARs, and carbonyl content. ED patients presented a Th2 immune pattern, while AD exhibited Th1 status. CRP levels and ferritin were increased in both stages of disease. Leukocytes burst impairment was observed in both the groups. Plasma iron levels were significantly elevated in AD. The data obtained indicated that oxidative stress enhancement and immune response impairment may be necessary to ensure cancer progression to advanced stages and may result from both host and tumor inflammatory mediators.

Asunto(s)

Neoplasias de la Mama/inmunología , Neoplasias de la Mama/metabolismo , Adulto , Anciano , Neoplasias de la Mama/patología , Citocinas/sangre , Femenino , Humanos , Mediadores de Inflamación/sangre , Peroxidación de Lípido , Persona de Mediana Edad , Estadificación de Neoplasias , Óxido Nítrico/sangre , Oxidación-Reducción , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/metabolismo , Adulto Joven

RESUMEN

The aims of the present study were to report the frequency of metabolic syndrome in systemic lupus erythematosus (SLE); to verify differences in inflammatory biomarkers and oxidative stress in SLE patients with or without metabolic syndrome; and to assess which metabolic syndrome components are associated with oxidative stress and disease activity. The study included 58 SLE patients and 105 controls. SLE patients were divided in two groups, with and without metabolic syndrome. 41.4% patients met the criteria for metabolic syndrome compared with 10.5% controls. Patients with SLE and metabolic syndrome had significantly raised serum uric acid, C-reactive protein (CRP), lipid hydroperoxides, and protein oxidation when compared with patients with SLE without metabolic syndrome. Lipid hydroperoxides were correlated with CRP, whereas protein oxidation was associated with waist circumference and uric acid. There was a positive association between serum C3 and C4 and glucose and between C3 and CRP. SLE disease activity index (SLEDAI) scores were positively correlated with body mass index (BMI) and waist circumference (WC). In conclusion, SLE patients have a high prevalence of metabolic syndrome and this syndrome directly contributes to increase inflammatory status and oxidative stress. Inflammatory processes, being overweight/obese, and uric acid may favor oxidative stress increases in patients with SLE and metabolic syndrome. C3 and C4 may have a positive acute-phase protein behavior in patients with SLE.

Asunto(s)

Biomarcadores/metabolismo , Inflamación , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/inmunología , Síndrome Metabólico/sangre , Síndrome Metabólico/inmunología , Estrés Oxidativo , Proteínas de Fase Aguda/metabolismo , Adulto , Proteína C-Reactiva/metabolismo , Comorbilidad , Femenino , Humanos , Inflamación/sangre , Inflamación/inmunología , Peroxidación de Lípido , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/fisiopatología , Masculino , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Obesidad , Sobrepeso , Factores de Riesgo , Ácido Úrico/sangre

RESUMEN

Oxidative stress exerts an important role on the pathophysiological mechanisms of systemic lupus erythematosus (SLE). This study investigated oxidative stress in patients with SLE and its correlation with disease activity, corticosteroid therapy, and liver function biomarkers. The study included 58 patients with SLE and 105 healthy volunteers. Patients showed oxidative stress increase evaluated by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH), advanced oxidation protein products (AOPP), and nitric oxide metabolites. C-reactive protein (CRP) was associated with CL-LOOH and with AOPP. Aspartate aminotransferase correlated significantly with CL-LOOH and with AOPP. Patients with disease activity showed an inverse significant correlation of daily prednisone doses and CL-LOOH and a direct correlation with total antioxidant capacity. In conclusion, patients with SLE have persistent lipoperoxidation and protein oxidation even with inactive disease or mild disease activity. The significant correlation between oxidative stress and CRP suggests that, despite clinical remission, the persistence of an inflammatory condition favors oxidative stress. Oxidative stress was associated with liver enzymes, and this relationship seems to support the hypothesis of drug-induced oxidative stress with consequent liver injury. In relation to non-active disease, patients with active SLE did not present oxidative stress and antioxidant capacity changes, due to the antioxidant drugs used in SLE treatment, especially prednisone.

Asunto(s)

Lupus Eritematoso Sistémico/metabolismo , Estrés Oxidativo , Corticoesteroides/uso terapéutico , Adulto , Antioxidantes/uso terapéutico , Biomarcadores/metabolismo , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Femenino , Humanos , Mediadores de Inflamación/metabolismo , Peroxidación de Lípido , Hígado/lesiones , Hígado/fisiopatología , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/fisiopatología , Masculino , Persona de Mediana Edad , Óxido Nítrico/metabolismo

RESUMEN

Metabolic syndrome (MS) is a multifactorial disease involving inflammatory activity and endothelial dysfunction. The aim of the present study was to evaluate the relationship between the changes in lipoperoxidation, in immunological and biochemical parameters and nitric oxide metabolite (NOx) levels in MS patients. Fifty patients with MS (4 males/46 females) and 50 controls (3 males/47 females) were studied. Compared to control (Mann-Whitney test), MS patients presented higher serum levels (P < 0.05) of fibrinogen: 314 (185-489) vs 262 (188-314) mg/dL, C-reactive protein (CRP): 7.80 (1.10-46.50) vs 0.70 (0.16-5.20) mg/dL, interleukin-6: 3.96 (3.04-28.18) vs 3.33 (2.55-9.63) pg/mL, uric acid: 5.45 (3.15-9.65) vs 3.81 (2.70-5.90) mg/dL, and hydroperoxides: 20,689 (19,076-67,182) vs 18,636 (15,926-19,731) cpm. In contrast, they presented lower (P < 0.05) adiponectin: 7.11 (3.19-18.22) vs 12.31 (9.11-27.27) µg/mL, and NOx levels: 5.69 (2.36-8.18) vs 6.72 (5.14-12.43) µM. NOx was inversely associated (Spearman’s rank correlation) with body mass index (r = -0.2858, P = 0.0191), insulin resistance determined by the homeostasis model assessment (r = -0.2530, P = 0.0315), CRP (r = -0.2843, P = 0.0171) and fibrinogen (r = -0.2464, P = 0.0413), and positively correlated with hydroperoxides (r = 0.2506, P = 0.0408). In conclusion, NOx levels are associated with obesity, insulin resistance, oxidative stress, and inflammatory markers. The high uric acid levels together with reactive oxygen species generation may be responsible for the reduced NO levels, which in turn lead to endothelial dysfunction. The elevated plasma chemiluminescence reflecting both increased plasma oxidation and reduced antioxidant capacity may play a role in the MS mechanism.

Asunto(s)

Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adiponectina/sangre , Endotelio Vascular/metabolismo , Resistencia a la Insulina/inmunología , Síndrome Metabólico/sangre , Óxido Nítrico/sangre , Estrés Oxidativo/inmunología , Antioxidantes/metabolismo , Índice de Masa Corporal , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Inflamación/sangre , Peroxidación de Lípido , Síndrome Metabólico/inmunología , Obesidad/sangre , Ácido Úrico/sangre

RESUMEN

Metabolic syndrome (MS) is a multifactorial disease involving inflammatory activity and endothelial dysfunction. The aim of the present study was to evaluate the relationship between the changes in lipoperoxidation, in immunological and biochemical parameters and nitric oxide metabolite (NOx) levels in MS patients. Fifty patients with MS (4 males/46 females) and 50 controls (3 males/47 females) were studied. Compared to control (Mann-Whitney test), MS patients presented higher serum levels (P < 0.05) of fibrinogen: 314 (185-489) vs 262 (188-314) mg/dL, C-reactive protein (CRP): 7.80 (1.10-46.50) vs 0.70 (0.16-5.20) mg/dL, interleukin-6: 3.96 (3.04-28.18) vs 3.33 (2.55-9.63) pg/mL, uric acid: 5.45 (3.15-9.65) vs 3.81 (2.70-5.90) mg/dL, and hydroperoxides: 20,689 (19,076-67,182) vs 18,636 (15,926-19,731) cpm. In contrast, they presented lower (P < 0.05) adiponectin: 7.11 (3.19-18.22) vs 12.31 (9.11-27.27) µg/mL, and NOx levels: 5.69 (2.36-8.18) vs 6.72 (5.14-12.43) µM. NOx was inversely associated (Spearman's rank correlation) with body mass index (r = -0.2858, P = 0.0191), insulin resistance determined by the homeostasis model assessment (r = -0.2530, P = 0.0315), CRP (r = -0.2843, P = 0.0171) and fibrinogen (r = -0.2464, P = 0.0413), and positively correlated with hydroperoxides (r = 0.2506, P = 0.0408). In conclusion, NOx levels are associated with obesity, insulin resistance, oxidative stress, and inflammatory markers. The high uric acid levels together with reactive oxygen species generation may be responsible for the reduced NO levels, which in turn lead to endothelial dysfunction. The elevated plasma chemiluminescence reflecting both increased plasma oxidation and reduced antioxidant capacity may play a role in the MS mechanism.

Asunto(s)

Adiponectina/sangre , Endotelio Vascular/metabolismo , Resistencia a la Insulina/inmunología , Síndrome Metabólico/sangre , Óxido Nítrico/sangre , Estrés Oxidativo/inmunología , Adulto , Antioxidantes/metabolismo , Biomarcadores/sangre , Índice de Masa Corporal , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inflamación/sangre , Peroxidación de Lípido , Masculino , Síndrome Metabólico/inmunología , Persona de Mediana Edad , Obesidad/sangre , Ácido Úrico/sangre

RESUMEN

The mechanisms by which Pb(2+) induces hemolysis are not completely understood. For this reason, the involvement of oxidative stress in the mechanism of Pb(2+)-induced pre-hemolytic lesion was investigated by exposing RBC to Pb(2+) in vitro and then separating the intact non-hemolysed RBC. Oxidative stress was investigated on human RBCs by tert-butyl hydroperoxide-initiated chemiluminescence method (CL). Our results revealed that lead-induced time and concentration-dependent hemolysis and CL time curves showed a very narrow correlation each other. GSH oxidation to GSSG and the stress index also increased significantly. Treatment of lead-exposed RBC with desferrioxamine, an iron-chelating agent or the chain-breaking antioxidant, Trolox, quenched light emission and inhibited hemolysis dramatically. Mannitol and sodium formate, (*)OH scavengers, on the contrary, did not inhibit CL or hemolysis, significantly. These data indicate that lead-induced lipid peroxide formation is mediated by a metal-driven Fenton reaction but do not support the direct involvement of hydroxyl radicals in this process. By contrast, our results revealed a decrease in light emission and decreased hemolysis in the presence of histidine, a singlet oxygen scavenger. Our results suggest that membrane damage and hemolysis of RBC are mediated by Pb(2+) through free radical reactions and that singlet oxygen plays a significant role in this process.

Asunto(s)

Membrana Eritrocítica/efectos de los fármacos , Eritrocitos/efectos de los fármacos , Hemólisis/efectos de los fármacos , Compuestos Organometálicos/toxicidad , Antioxidantes/farmacología , Cromanos/farmacología , Deferoxamina/farmacología , Eritrocitos/metabolismo , Formiatos/farmacología , Radicales Libres/metabolismo , Glutatión/metabolismo , Hemoglobinas/metabolismo , Hemostáticos/farmacología , Histidina/farmacología , Humanos , Mediciones Luminiscentes/métodos , Manitol/farmacología , Estrés Oxidativo/fisiología , Sideróforos/farmacología , terc-Butilhidroperóxido/metabolismo

RESUMEN

This study evaluated two cases of Apert's syndrome, through phonological, cognitive, and neuropsychological instruments and correlated the results to complementary exams. In short, this study reveals the necessity of application of neuropsychological, cognitive and phonological evaluation and correlation of the results with complementary testings because significant differences can be present in the Apert's syndrome.

Asunto(s)

Acrocefalosindactilia/fisiopatología , Trastornos de la Articulación/diagnóstico , Cognición/fisiología , Pruebas Neuropsicológicas , Habla/fisiología , Acrocefalosindactilia/psicología , Niño , Femenino , Humanos , Lóbulo Temporal/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único/métodos