Association of lead, cadmium and mercury with paraoxonase 1 activity and malondialdehyde in a general population in Southern Brazil.

Metal exposure is associated with increased oxidative stress (OS), which is considered an underlying mechanism of metal-induced toxicity. Malondialdehyde (MDA) is a final product of lipid peroxidation, and it has been extensively used to evaluate metal-induced OS. Pro-oxidant effects produced by metals can be mitigated by paraoxonase 1 (PON1), an antioxidant enzyme known to prevent cardiovascular disease and atherosclerosis. Among other factors, the Q192R polymorphism and the exposure to heavy metals have been known to alter PON1 activity. Here, we evaluated the association of blood lead (Pb), cadmium (Cd) and mercury (Hg) levels with PON1 activity, and with MDA concentrations in a randomly selected sample of Brazilian adults aged 40 years or older, living in an urban area in Southern Brazil. A total of 889 subjects were evaluated for blood Pb and Cd levels, and 832 were tested for Hg. Geometric mean of blood Pb, Cd and Hg was 1.93µg/dL, 0.06µg/L and 1.40µg/L, respectively. PON1 activity was significantly different among various genotypes: QQ (PON1=121.4U/mL), QR (PON1=87.5U/mL), and RR (PON1=55.2U/mL), p<0.001. PON1 genotypes were associated only with Cd blood levels. Those with QR genotype had Cd concentrations higher (0.07µg/L) than those with the RR genotype (0.04µg/L) with p=0.034. However, PON1 activity was not significantly associated with metal concentrations. Cluster analysis showed that men who reported to be current smokers and drinkers with higher blood Pb and Cd levels, had significantly lower PON1 activity than non-smokers or -drinkers, and women with lower Pb and Cd levels. RR genotype carriers had lower PON1 activity than those with the QR genotype, and had higher levels of Pb and Cd compared with other genotype carriers. For blood Hg, no association with PON1 activity or genotype was noted. We found low levels of Pb, Cd and Hg in environmentally exposed Brazilian adults. Cd concentrations were increased in subjects with QR genotype. Those with RR genotype had lower PON1 activity and higher levels of Pb and Cd than other genotype carriers. The results of cluster analysis suggested that smoking status exerts a significant influence on PON1 activity. Other studies with environmentally exposed populations are required to further clarify whether low blood levels of metals influence OS biomarkers.

Association between blood lead and blood pressure: a population-based study in Brazilian adults.

BACKGROUND: Environmental lead exposure among adults may increase blood pressure and elevate the risk of hypertension. The availability of data on blood lead levels (BLL) in adult Brazilian population is scarce and population-based studies are important for screening the population exposure and also to evaluate associations with adverse health effects. The goal of this study was to examine the association of BLL with blood pressure and hypertension in a population-based study in a city in Southern Brazil. METHODS: A total of 948 adults, aged 40 years or older, were randomly selected. Information on socioeconomic, dietary, lifestyle and occupational background was obtained by orally administered household interviews. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured according to the guidelines VI Brazilian Guidelines on Hypertension. BLL were measured by inductively coupled plasma mass spectrometry technique. Multiple linear and logistic regression models were performed to evaluate associations of BLL with SBP and DBP, and with the chance of hypertension and of elevated SBP and DBP. RESULTS: The geometric mean of BLL was 1.97 µg/dL (95%CI:1.90-2.04 µg/dL). After multivariable adjustment, participants in the quartile 4 of blood lead presented 0.06 mm/Hg (95%CI, 0.04-0.09) average difference in DBP comparing with those in quartile 1. Participants in the 90th percentile of blood lead distribution had 0.07 mmHg (95% CI, 0.03 to 0.11) higher DBP compared with those participants in the 10th percentile of blood lead. The adjusted OR for hypertension was 2.54 (95% CI, 1.17-5.53), comparing the highest to the lowest blood lead quartiles. Compared with participants in the 10th percentile of blood lead, participants in the 90th percentile presented higher OR for hypertension (OR: 2.77; 95% CI, 1.41 to 5.46). CONCLUSION: At low concentrations, BLL were positively associated with DBP and with the odds for hypertension in adults aged 40 or older. It is important to enforce lead exposure monitoring and the enactment of regulatory laws to prevent lead contamination in urban settings.

Association between soy and green tea (Camellia sinensis) diminishes hypercholesterolemia and increases total plasma antioxidant potential in dyslipidemic subjects.

OBJECTIVE: To evaluate the hypolipemic and antioxidant effects of soy and green tea alone and/or in association in dyslipidemic subjects. METHODS: One hundred dyslipidemic individuals were allocated into four groups. The soy group ingested 50 g of soy (kinako) daily, and the green tea group ingested 3 g of green tea in 500 mL of water per day. A third group ingested 50 g of soy and 3 g of green tea daily, and the control group had a hypocholesterolemic diet. Evaluations were performed at baseline and after 45 and 90 d. Plasma levels of total cholesterol, high-density lipoprotein, and triacylglycerols were evaluated by automated methods. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation. LDL was isolated by ultracentrifugation. Total plasma antioxidant capacity and plasma levels of total lipid hydroperoxides and those linked to LDL were evaluated by chemiluminescence. The results were expressed as median values and their 25th to 75th percentiles, with a 5% level of significance. RESULTS: No significant difference occurred in LDL, high-density lipoprotein cholesterol, and triacylglycerol levels across groups. However, a statistically significant difference in total cholesterol occurred within the soy/green tea group 45 and 90 d after intervention. No statistically significant difference occurred in plasma levels of lipid hydroperoxides or those linked to LDL in any of the groups studied. All the groups that used soy and/or green tea presented increased total plasma antioxidant potential. CONCLUSION: Soy and green tea, alone or in combination, increased the total antioxidant potential of hypercholesterolemic patients, whereas only the combination decreased total cholesterol levels.

Indices of insulin resistance and glucotoxicity are not associated with bipolar disorder or major depressive disorder, but are differently associated with inflammatory, oxidative and nitrosative biomarkers.

BACKGROUND: Insulin resistance (IR) is a key factor in diabetes mellitus, metabolic syndrome (MetS) and obesity and may occur in mood disorders and tobacco use disorder (TUD), where disturbances of immune-inflammatory, oxidative and nitrosative stress (IO&NS) pathways are important shared pathophysiological pathways. METHODS: This study aimed to a) examine IR and ß-cell function as measured by the homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity and ß cell function (HOMA-B) and glucotoxicity (conceptualized as increased glucose levels versus lowered HOMA-B values) in 74 participants with major depressive disorder (MDD) and bipolar disorder, with and or without MetS and TUD, versus 46 healthy controls, and b) whether IR is associated with IO&NS biomarkers, including nitric oxide metabolites (NOx), lipid hydroperoxides (LOOH), plasma advanced oxidation protein products (AOPP), C-reactive protein (CRP), haptoglobin (Hp) and uric acid. RESULTS: Mood disorders are not associated with changes in IR or glucotoxicity, although the number of mood episodes may increase IR. 47.8% of the variance in HOMA-IR is explained by AOPP and body mass index (BMI, both positively) and NOx, Hp and TUD (all inversely). 43.2% of the variance in HOMA-B is explained by NOx, Hp and age (all inversely associated) and higher BMI and sex. The glucotoxic index is strongly associated with NOx, Hp and BMI (positively), male gender and lower education. LIMITATIONS: This is a cross-sectional study and therefore we cannot draw firm conclusions on causal associations. CONCLUSIONS: Activated IO&NS pathways (especially increased Hp and NOx) increase glucotoxicity and exert very complex effects modulating IR. Mood disorders are not associated with increased IR.

Envolvimento das quimiocinas CCL2 e CCL5 na patogênese do câncer de mama / Involvement of CCL2 and CCLS chemokines in breast cancer pathogenesis

No Brasil, o câncer de mama é o que mais causa mortes entre as mulheres com um risco de 51 casos a cada 100 mil mulheres. A metástase, principal causa de morte pelo câncer de mama, e dirigida a urna variedade de órgaos vitais, como ossos, pulmões, cerebra e fígado. Ocorre quando células tumorais geneticamente instáveis adaptam-se ao microambiente do tecido que esta distante do tumor primário. A natureza heterogênea da metástase no câncer de mama dificulta não apenas a cura, mas também a estimativa dos fatores de risco. A disseminação das células tumorais é realizada através da circulação sanguínea sistêmica atingindo outros órgãos. Tern sido verificado que essas células utilizam-se da expressão dos receptores de quimiocinas, para encontrar órgaos alvo que produzem um particular conjunto de quimiocinas. Mais recentemente, foi estabelecido que as células do câncer aproveitam-se da sinalização através dos receptores para quimiocinas para a iniciação e progressão do tumor primário e da metástase. Embora grande número de moléculas tenha sido implicada na metástase do câncer de mama, o mecanismo exato que determina a direção da migração parece incerto. Tem sido demonstrado que CCL2 e CCL5 estão expressas em grande quantidade pelas células tumorais do câncer de mama e são a causa da malignidade e metástase neste órgão. A expressão dessas duas quimiocinas pelas células do tumor de mama acompanha eventos de transformação maligna, e está associada com o curso avançado e progressão da doença. Desse modo, vários estudos sugerem que a determinação e o prognóstico das quimiocinas CCL2 e CCL5 será de grande para uma melhor identificação do risco de progressão e determinação das implicações terapêuuticas em pacientes com câncer de mama.

In Brazil, breast cancer is the major cause death among women with a risk of 51 cases to 100 thousand women. The metastasis, the main cause of death by breast cancer, is directed to a variety of vital organs such as bones, lungs, brain and liver. Occurs when genetically unstable tumor cells adapt to the microenvironment of the tissue that is distant from the primary tumor. The heterogeneous nature of metastasis in breast cancer is difficult not only for the definition of cure for this disease, but also to estimate their risk factors. The spread of tumor cells is achieved through the systemic bloodstream to reach other organs. It has been verified that these cells are used the expression of chemokine receptors to find on target organs that produce a particular set of chemokines. It was established that the cancer cells use the signaling through the receptors for chemokines in the initiation and progression of primary tumor and metastasis. Although large number of molecules has been implicated in metastasis of breast cancer, the exact mechanism that determines the direction of migration seems uncertain. In a review conducted recently, the authors argue that CCL2 and CCL5 are expressed in large amounts by tumor cells of breast cancer and are the cause of malignancy and metastasis in this organ. The expression of these chemokines by the tumor cells of breast accompanying events of malignant transformation, and is associated with the advanced course and progression of disease. Thus several studies suggest that the determination and validation of the prognostic value of the chemokines CCL2 and CCL5 will be of great value for better identification of risk of progression and determine the therapeutic implications in patients with breast cancer.