Ivana Beatrice Mânica da Cruz

Association between ischemia-modified albumin, lipids and inflammation biomarkers in patients with hypercholesterolemia.

OBJECTIVES The aim of this study was to evaluate the association between ischemia-modified albumin (IMA), lipids and inflammation biomarkers in patients with hypercholesterolemia, and the possible involvement of IMA in atheromatous plaque development and oxidative stress. DESIGN AND METHODS Glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, oxidized LDL (ox-LDL), ox-LDL autoantibodies, high-sensitivity C reactive protein (hs-CRP), and IMA were measured in 37 subjects with hypercholesterolemia and 37 controls. RESULTS Total cholesterol, LDL cholesterol, triglycerides, ox-LDL, ox-LDL autoantibodies, hs-CRP, and IMA were higher in the hypercholesterolemia group, and HDL cholesterol levels were lower in this group. We observed significant correlations between IMA and total cholesterol, LDL cholesterol, ox-LDL antibodies, and hs-CRP levels. Significant correlations were also observed between hs-CRP and total cholesterol, HDL cholesterol, LDL cholesterol, ox-LDL, ox-LDL autoantibodies, and triglycerides. CONCLUSIONS Hypercholesterolemia is associated with an increase in inflammatory and oxidative stress biomarkers, and it also reduces the capacity of albumin to bind cobalt owing to ischemia, resulting in an increased IMA. IMA formation appears to be associated with oxidative stress and atheromatous plaque development.

Toxicological effects of ultraviolet radiation on lymphocyte cells with different manganese superoxide dismutase Ala16Val polymorphism genotypes

The aim of this study was to investigate whether there is a differential response of lymphocytes from healthy MnSOD genotype subjects to oxidative stress. We used UV radiation as a toxic agent due to its genotoxic effects associated with chromosome aberrations caused by breaks in the DNA strands. Cellular growth rate, cell viability, mitotic index, chromosomal instability and biomarkers of oxidative metabolism were analysed in lymphocyte cells from healthy adults with different Ala16Val MnSOD polymorphisms that produce tree genotypes: AA, VV and AV. We found a differential response to UV exposure in cultures of lymphocyte cells from Ala16Val genotype donors. In general, AA cell cultures presented higher viability and mitotic index and lower TBARS levels than VV and AV cells for both the control and UV exposure groups. However, when we compared the DNA damage among the three genotypes, AA lymphocyte cells presented the highest damage from UV exposure. These data suggest that the Ala16Val polymorphism affects the response of cellular oxidative metabolism in different ways.

Oxidative stress in hypercholesterolemia and its association with Ala16Val superoxide dismutase gene polymorphism

OBJECTIVES To investigate the role of the oxidative stress and the antioxidant system as well as the influence of the manganese superoxide dismutase (Ala16Val) polymorphism on hypercholesterolemia. DESIGN AND METHODS Levels of glucose, lipid, high-sensitivity C reactive protein (hs-CRP), thiobarbituric acid reactive substances (TBARS), carbonyl protein, thiols, reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and vitamin C, vitamin E, as well as the presence of the manganese superoxide dismutase (Ala16Val) polymorphism were determined in 40 subjects with hypercholesterolemia and 40 controls. RESULTS Lipid profile, hs-CRP, glucose, TBARS, carbonyl protein, CAT, and vitamin E were significantly higher in subjects with hypercholesterolemia. In contrast, GSH and SOD were lower. TBARS, carbonyl protein, thiols, CAT, and vitamin E were significantly higher in hypercholesterolemic subjects with VV genotype for MnSOD, while GSH, SOD, and vitamin C were lower in these subjects. CONCLUSIONS We suggest an association between the genotypes of MnSOD, hypercholesterolemia, and oxidative stress biomarkers.

Ischemia-modified albumin as an oxidative stress biomarker in obesity.

OBJECTIVE We evaluated the levels of ischemia-modified albumin (IMA) and its association with body mass index (BMI) in patients who are obese. DESIGN AND METHODS Fasting glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, malondialdehyde, and IMA levels were assessed in 148 subjects. RESULTS IMA, malondialdehyde, and fasting glucose levels were significantly higher while the HDL cholesterol levels were lower in obese population. CONCLUSIONS IMA levels increase in overweight and obese subjects.

Habitual Intake of Guaraná and Metabolic Morbidities: An Epidemiological Study of an Elderly Amazonian Population

The aim of the present study was to evaluate the associations of metabolic disorders and anthropometric and biochemical biomarkers of lipid, glucose and oxidative metabolism and the habitual ingestion of guaraná (Paullinia cupana, Mart. Var. sorbilis) by an elderly population residing in the Amazon Riverine region of the Maués municipality (Brazil). A case‐controlled study was performed that included 637 elderly (≥60 years of age) patients classified as either those who habitually drank guaraná (GI, n = 421) or those who never drank guaraná (NG, n = 239) based upon their self‐reported intake of guaraná. Indeed, the prevalence of various metabolic disorders was associated with guaraná ingestion. The prevalence of hypertension, obesity and metabolic syndrome in the GI group was lower than the prevalence found in the NG group. The NG group exhibited lower systolic and diastolic blood pressure values. The males in the GI group exhibited a lower waist circumference, on average, than the circumference found in the NG group, whereas the females in the GI group had lower cholesterol (total and LDL‐c) levels than the control cohort. Additionally, a significant association was found between lower levels of advanced oxidative protein product (AOPP) and habitual guaraná consumption. The results constitute the first epidemiological study to suggest a potentially protective effect of habitual guaraná ingestion against metabolic disorders in elderly subjects. Copyright

Quercetin protects the impairment of memory and anxiogenic-like behavior in rats exposed to cadmium: Possible involvement of the acetylcholinesterase and Na+,K+-ATPase activities

The present study investigated the effects of quercetin in the impairment of memory and anxiogenic-like behavior induced by cadmium (Cd) exposure. We also investigated possible alterations in acetylcholinesterase (AChE), Na(+),K(+)-ATPase and δ-aminolevulinate dehydratase (δ-ALA-D) activities as well as in oxidative stress parameters in the CNS. Rats were exposed to Cd (2.5mg/kg) and quercetin (5, 25 or 50mg/kg) by gavage for 45days. Animals were divided into eight groups (n=10-14): saline/control, saline/Querc 5mg/kg, saline/Querc 25mg/kg, saline/Querc 50mg/kg, Cd/ethanol, Cd/Querc 5mg/kg, Cd/Querc 25mg/kg and Cd/Querc 50mg/kg. Results demonstrated that Cd impaired memory has an anxiogenic effect. Quercetin prevented these harmful effects induced by Cd. AChE activity decreased in the cerebral cortex and hippocampus and increased in the hypothalamus of Cd-exposed rats. The Na(+),K(+)-ATPase activity decreased in the cerebral cortex, hippocampus and hypothalamus of Cd-exposed rats. Quercetin prevented these effects in AChE and Na(+),K(+)-ATPase activities. Reactive oxygen species production, thiobarbituric acid reactive substance levels, protein carbonyl content and double-stranded DNA fractions increased in the cerebral cortex, hippocampus and hypothalamus of Cd-exposed rats. Quercetin totally or partially prevents these effects caused by Cd. Total thiols (T-SHs), reduced glutathione (GSH), and reductase glutathione (GR) activities decreased and glutathione S-transferase (GST) activity increased in Cd exposed rats. Co-treatment with quercetin prevented reduction in T-SH, GSH, and GR activities and the rise of GST activity. The present findings show that quercetin prevents alterations in oxidative stress parameters as well as AChE and Na(+),K(+)-ATPase activities, consequently preventing memory impairment and anxiogenic-like behavior displayed by Cd exposure. These results may contribute to a better understanding of the neuroprotective role of quercetin, emphasizing the influence of this flavonoid in the diet for human health, possibly preventing brain injury associated with Cd intoxication.

The MnSOD Ala16Val SNP: Relevance to human diseases and interaction with environmental factors

Abstract The relevance of reactive oxygen species (ROS) production relies on the dual role shown by these molecules in aerobes. ROS are known to modulate several physiological phenomena, such as immune response and cell growth and differentiation; on the other hand, uncontrolled ROS production may cause important tissue and cell damage, such as deoxyribonucleic acid oxidation, lipid peroxidation, and protein carbonylation. The manganese superoxide dismutase (MnSOD) antioxidant enzyme affords the major defense against ROS within the mitochondria, which is considered the main ROS production locus in aerobes. Structural and/or functional single nucleotide polymorphisms (SNP) within the MnSOD encoding gene may be relevant for ROS detoxification. Specifically, the MnSOD Ala16Val SNP has been shown to alter the enzyme localization and mitochondrial transportation, affecting the redox status balance. Oxidative stress may contribute to the development of type 2 diabetes, cardiovascular diseases, various inflammatory conditions, or cancer. The Ala16Val MnSOD SNP has been associated with these and other chronic diseases; however, inconsistent findings between studies have made difficult drawing definitive conclusions. Environmental factors, such as dietary antioxidant intake and exercise have been shown to affect ROS metabolism through antioxidant enzyme regulation and may contribute to explain inconsistencies in the literature. Nevertheless, whether environmental factors may be associated to the Ala16Val genotypes in human diseases still needs to be clarified.

The protective effects of guaraná extract (Paullinia cupana) on fibroblast NIH-3T3 cells exposed to sodium nitroprusside.

The antioxidant effects of the hydro-alcoholic guaraná extract (Paullinia cupana var. sorbilis Mart.) on nitric oxide (NO) and other compounds generated from the degradation of sodium nitroprusside (SNP) in an embryonic fibroblast culture (NIH-3T3 cells) were evaluated. The guaraná bioactive compounds were initially determined by high-performance liquid chromatography: caffeine=12.240 mg/g, theobromine=6.733 mg/g and total catechins=4.336 mg/g. Cells were exposed to 10 μM SNP during a 6 h period because the cells exhibited >90% mortality at this concentration. Guaraná was added to the cultures in five concentrations (0.5, 1, 5, 10 and 20 mg/mL). The guaraná antioxidant effect was evaluated by viability assays, biochemical oxidation [lipid peroxidation, catalase and superoxide dismutase (SOD) activity] and genotoxicity (DNA Comet assay) analysis. Additionally, oxidative stress was evaluated by a 2,7-dihydrodichlorofluorescein diacetate fluorescence assay. Guaraná reverted the SNP toxicity mainly at lower concentrations (<5 mg), which decreased cell mortality, lipid peroxidation, DNA damage and cell oxidative stress as well as increased the SOD levels. These results demonstrate that guaraná has an antioxidant effect on NO metabolism in situations with higher cellular NO levels.

Antimicrobial activity of Schinus lentiscifolius (Anacardiaceae).

ETHNOPHARMACOLOGICAL RELEVANCE Schinus lentiscifolius Marchand (syn. Schinus weinmannifolius Engl) is a plant native to Rio Grande do Sul (Southern Brazil) and has been used in Brazilian traditional medicine as antiseptic and antimicrobial for the treatment of many different health problems as well as to treat leucorrhea and to assist in ulcer and wound healing. Although it is a plant widely used by the population, there are no studies proving this popular use. MATERIAL AND METHODS The crude aqueous extract, the crude neutral methanol extract, fractions prepared from this extract (n-hexane, ethyl acetate, and n-butanol), pure compounds isolated from these fractions, and derivatives were investigated in vitro for antimicrobial activities against five Gram positive bacteria: Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus pyogenes, three Gram negative bacteria: Escherichia coli, Pseudomonas aeruginosa, and Shigella sonnei, and four yeasts: Candida albicans, Candida tropicalis, Cryptococcus neoformans, and Saccharomyces cerevisiae. The isolated compound moronic acid, which is the most active, was tested against a range of other bacteria such as two Gram positive bacteria, namely, Bacillus cereus, Enterococcus spp, and six Gram negative bacteria, namely, Burkholderia cepacia, Providencia stuartii, Morganella morganii, Enterobacter cloacae, Enterobacter aerogenes, and Proteus mirabilis. RESULTS The leaf aqueous extract (decoction) of Schinus lentiscifolius showed a broad spectrum of antibacterial activity, ranging from 125 to 250 μg/ml (MIC) against the tested bacteria and fungi. The n-hexane extract, despite being very little active against bacteria, showed an excellent antifungal activity, especially against Candida albicans (MIC=25 μg/ml), Candida tropicalis (MIC=15.5 μg/ml), and Cryptococcus neoformans, (MIC=15.5 μg/ml). From the acetate fraction (the most active against bacteria), compounds 1-6 were isolated: nonadecanol (1), moronic acid (2), gallic acid methyl ester (3), gallic acid (4), quercetin (5) and quercitrin (6). The minimal inhibitory concentration (MIC) of moronic acid between 1.5 and 3 μg/ml against most of the tested bacteria shows that it is one of the metabolites responsible for the antibacterial activity of Schinus lentiscifolius. CONCLUSION The antimicrobial activity and some constituents of Schinus lentiscifolius are reported for the first time. The results of the present study provide scientific basis for the popular use of Schinus lentiscifolius for a number of different health problems.

Assessment of Inflammatory and Oxidative Biomarkers in Obesity and Their Associations with Body Mass Index

The aim of this study was to evaluate the inflammatory and oxidative biomarkers’ levels in obese subjects and their associations with body mass index (BMI), in order to investigate the role of these biomarkers in obesity. Fasting glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, apolipoprotein A, apolipoprotein B, albumin, urinary albumin, creatinine, glomerular filtration rate, interleukin-6 (IL-6), nitrate/nitrite (NOx), and ischemia-modified albumin (IMA) were measured in 93 subjects divided according to different BMI. IL-6, urinary albumin, and IMA levels were significantly higher in obese subjects. However, the levels of NOx were significantly lower in this population. Significant correlations between BMI and IL-6 (r = 0.326, P = 0.002), NOx (r = −0.249, P = 0.021), urinary albumin (r = 0.270, P = 0.008), and IMA (r = 0.286, P = 0.005) were reported. We have shown an increase of IL-6, urinary albumin, and IMA combined with lower levels of NOx in obese patients and an association between of these biomarkers with BMI, suggesting a possible interplay of oxidative stress, inflammation, and endothelial dysfunction state in obesity.