Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus

Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1'kg/m2], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4'mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality.

Antioxidant effect of 4-nerolidylcatechol and α-tocopherol in erythrocyte ghost membranes and phospholipid bilayers

4-Nerolidylcatechol (4-NC) is found in Pothomorphe umbellataroot extracts and is reported to have a topical protective effect against UVB radiation-induced skin damage, toxicity in melanoma cell lines, and antimalarial activity. We report a comparative study of the antioxidant activity of 4-NC and α-tocopherol against lipid peroxidation initiated by two free radical-generating systems: 2,2′-azobis(2-aminopropane) hydrochloride (AAPH) and FeSO4/H2O2, in red blood cell ghost membranes and in egg phosphatidylcholine (PC) vesicles. Lipid peroxidation was monitored by membrane fluidity changes assessed by electron paramagnetic resonance spectroscopy of a spin-labeled lipid and by the formation of thiobarbituric acid-reactive substances. When lipoperoxidation was initiated by the hydroxyl radical in erythrocyte ghost membranes, both 4-NC and α-tocopherol acted in a very efficient manner. However, lower activities were observed when lipoperoxidation was initiated by the peroxyl radical; and, in this case, the protective effect of α-tocopherol was lower than that of 4-NC. In egg PC vesicles, malondialdehyde formation indicated that 4-NC was effective against lipoperoxidation initiated by both AAPH and FeSO4/H2O2, whereas α-tocopherol was less efficient in protecting against lipoperoxidation by AAPH, and behaved as a pro-oxidant for FeSO4/H2O2. The DPPH (2,2-diphenyl-1-picrylhydrazyl) free-radical assay indicated that two free radicals were scavenged per 4-NC molecule, and one free radical was scavenged per α-tocopherol molecule. These data provide new insights into the antioxidant capacity of 4-NC, which may have therapeutic applications for formulations designed to protect the skin from sunlight irradiation.

Effect of penehyclidine hydrochloride on β-arrestin-1 expression in lipopolysaccharide-induced human pulmonary microvascular endothelial cells

β-arrestins are expressed proteins that were first described, and are well-known, as negative regulators of G protein-coupled receptor signaling. Penehyclidine hydrochloride (PHC) is a new anti-cholinergic drug that can inhibit biomembrane lipid peroxidation, and decrease cytokines and oxyradicals. However, to date, no reports on the effects of PHC on β-arrestin-1 in cells have been published. The aim of this study was to investigate the effect of PHC on β-arrestin-1 expression in lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cells (HPMEC). Cultured HPMEC were pretreated with PHC, followed by LPS treatment. Muscarinic receptor mRNAs were assayed by real-time quantitative PCR. Cell viability was assayed by the methyl thiazolyl tetrazolium (MTT) conversion test. The dose and time effects of PHC on β-arrestin-1 expression in LPS-induced HPMEC were determined by Western blot analysis. Cell malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were measured. It was found that the M3 receptor was the one most highly expressed, and was activated 5 min after LPS challenge. Furthermore, 2 μg/mL PHC significantly upregulated expression of β-arrestin-1 within 10 to 15 min. Compared with the control group, MDA levels in cells were remarkably increased and SOD activities were significantly decreased in LPS pretreated cells, while PHC markedly decreased MDA levels and increased SOD activities. We conclude that PHC attenuated ROS injury by upregulating β-arrestin-1 expression, thereby implicating a mechanism by which PHC may exert its protective effects against LPS-induced pulmonary microvascular endothelial cell injury.

Therapeutic concentration of morphine reduces oxidative stress in glioma cell line

Morphine is a potent analgesic opioid used extensively for pain treatment. During the last decade, global consumption grew more than 4-fold. However, molecular mechanisms elicited by morphine are not totally understood. Thus, a growing literature indicates that there are additional actions to the analgesic effect. Previous studies about morphine and oxidative stress are controversial and used concentrations outside the range of clinical practice. Therefore, in this study, we hypothesized that a therapeutic concentration of morphine (1 μM) would show a protective effect in a traditional model of oxidative stress. We exposed the C6 glioma cell line to hydrogen peroxide (H2O2) and/or morphine for 24 h and evaluated cell viability, lipid peroxidation, and levels of sulfhydryl groups (an indicator of the redox state of the cell). Morphine did not prevent the decrease in cell viability provoked by H2O2 but partially prevented lipid peroxidation caused by 0.0025% H2O2 (a concentration allowing more than 90% cell viability). Interestingly, this opioid did not alter the increased levels of sulfhydryl groups produced by exposure to 0.0025% H2O2, opening the possibility that alternative molecular mechanisms (a direct scavenging activity or the inhibition of NAPDH oxidase) may explain the protective effect registered in the lipid peroxidation assay. Our results demonstrate, for the first time, that morphine in usual analgesic doses may contribute to minimizing oxidative stress in cells of glial origin. This study supports the importance of employing concentrations similar to those used in clinical practice for a better approximation between experimental models and the clinical setting.

Caryocar brasiliense camb protects against genomic and oxidative damage in urethane-induced lung carcinogenesis

The antioxidant effects of Caryocar brasiliense Camb, commonly known as the pequi fruit, have not been evaluated to determine their protective effects against oxidative damage in lung carcinogenesis. In the present study, we evaluated the role of pequi fruit against urethane-induced DNA damage and oxidative stress in forty 8-12 week old male BALB/C mice. An in vivo comet assay was performed to assess DNA damage in lung tissues and changes in lipid peroxidation and redox cycle antioxidants were monitored for oxidative stress. Prior supplementation with pequi oil or its extract (15 µL, 60 days) significantly reduced urethane-induced oxidative stress. A protective effect against DNA damage was associated with the modulation of lipid peroxidation and low protein and gene expression of nitric oxide synthase. These findings suggest that the intake of pequi fruit might protect against in vivo genotoxicity and oxidative stress.

Intensity of swimming exercise influences aortic reactivity in rats

Exercise is known to cause a vasodilatory response; however, the correlation between the vasorelaxant response and different training intensities has not been investigated. Therefore, this study evaluated the vascular reactivity and lipid peroxidation after different intensities of swimming exercise in rats. Male Wistar rats (aged 8 weeks; 250-300 g) underwent forced swimming for 1 h whilst tied to loads of 3, 4, 5, 6, and 8% of their body weight, respectively (groups G3, G4, G5, G6 and G8, respectively; n=5 each). Immediately after the test, the aorta was removed and suspended in an organ bath. Cumulative relaxation in response to acetylcholine (10−12-10−4 M) and contraction in response to phenylephrine (10−12-10−5 M) were measured. Oxidative stress was estimated by determining malondialdehyde concentration. The percentages of aorta relaxation were significantly higher in G3 (7.9±0.20), G4 (7.8±0.29), and G5 (7.9±0.21), compared to the control group (7.2±0.04), while relaxation in the G6 (7.4±0.25) and G8 (7.0±0.06) groups was similar to the control group. In contrast, the percentage of contraction was significantly higher in G6 (8.8 ±0.1) and G8 (9.7±0.29) compared to the control (7.1±0.1), G3 (7.3±0.2), G4 (7.2±0.1) and G5 (7.2±0.2%) groups. Lipid peroxidation levels in the aorta were similar to control levels in G3, G4 and G5, but higher in G6 and G8, and significantly higher in G8 (one-way ANOVA). These results indicate a reduction in vasorelaxing activity and an increase in contractile activity in rat aortas after high-intensity exercise, followed by an increase in lipid peroxidation.

Antioxidant activity in vivo and in vitro of Halimeda incrassata aqueous extracts

The aim of the present paper was to provide the evidences for the antioxidant activity in Halimeda incrassata (Ellis) Lamouroux aqueous extracts obtained after simple water extraction of the fresh algae at room temperature (23°C). Previously in the literature, only antioxidant activity associated to carotenoids fractions of seaweeds has been reported. From different species of seaweeds, Halimeda incrassata aqueous extract exhibited the highest antioxidant activity on the inhibition of TBARS formed during the spontaneous lipid peroxidation of rat brain homogenates with an IC50 of 0.340mg.mL-1. Halimeda incrassata aqueous extract (0.5mg.mL-1), was also capable of decreasing the in vitro generation of hydrogen peroxide by two distinct metabolic pathways involving glutamic and malonic acids. Also, Halimeda incrassata (at doses of 50, 100 and 200mg.Kg-1) showed a neuroprotective effect in vivo on the gerbil model of bilateral carotid occlusion because of decreasing the locomotor and exploratory activity induced by ischemia. In summary, Halimeda incrassata aqueous extracts exhibit antioxidant properties in different in vitro as well as in vivo models which could be explained by the presence of several hydrosoluble compounds. Further studies on this way are necessary to elucidate the precise structure of these compounds. Low toxicity of most seaweeds to humans, but particularly of Halimeda genus may favor its use as functional food.

Effect of processing and roasting on the antioxidant activity of coffee brews

The aim of this work was to evaluate the effect of processing and roasting on the antioxidant activity of coffee brews. Brews prepared with light, medium and dark roasted coffees were analyzed. The pH, total solids content, polyphenols content, reducing substances and chlorogenic acids content were determined. The antioxidant activity of aqueous extracts, the guaicol decolorizing and the capacity to inhibit lipid peroxidation were also analyzed. The antioxidant activity of coffee brews were concentration-dependent. A progressive antioxidant activity and polyphenols content was observed decreasing with roasting. The light roasted coffee showed the highest antioxidant activity and dark roasted coffee showed the lowest antioxidant activity. The results indicate that the ingestion of coffee brews prepared with light and medium roasted coffees might protect cells from oxidative stress damages.

Sensory evaluation and nutritional value of cakes prepared with whole flaxseed flour

The objective of this study was to evaluate the nutritional value, the oxidative stabilitiy, and consumer acceptance of cakes containing four different concentrations of flaxseed flour (5, 15, 30 and 45%) as partial replacement for wheat flour. The oxidative stability of polyunsaturated fatty acids was evaluated through the lipid peroxidation test (TBARS) in the flour and cakes. Linolenic acid was determined by gas chromatography as well as contents of protein, lipid, ash, and dietary fiber. Consumer acceptance was assessed using a structured hedonic scale of nine points. The oxidative stability of lipid flaxseeds was not affected by the heat treatment during flour processing and cake baking. Cakes made with 5, 15, and 30% of flaxseed flour, the most accepted by consumers, had dietary fiber levels ranging from 3.5 to 6.2 g and linolenic acid ranging from 445 to 2,500 mg.100 g-1 of the product. The cakes received claims of good and excellent source of dietary fiber and linolenic acid, respectively, both are bioactive compounds. The use of up to 30% of flaxseed flour in the preparation of cakes is a useful strategy to optimize the consumption of food rich in functional ingredients.

Effect of extracts from araticum (Annona crassiflora) on CCl4-induced liver damage in rats

The influence of ethanolic extracts of Annona crassiflora on the activities of hepatic antioxidant enzymes was examined. Extracts of A. crassiflora seeds and peel were administered orally (50 mg of galic acid equivalents.kg-1) to Wistar rats for 14 consecutive days followed by a single oral dose of carbon tetrachloride (CCl4, 2 g.kg-1). Lipid peroxidation and the activities of hepatic catalase (CAT), cytochromes P450 (CP450) and b5, glutathione peroxidase (GPx), glutathione reductase (GRed), superoxide dismutase (SOD), and the content of glutathione equivalents (GSH) were evaluated. The treatment with CCl4 increased lipid peroxidation, the level of GSH equivalents and the content of cytochrome b5 by 44, 140 and 32%, respectively, with concomitant reductions of 23, 34 and 39% in the activities of CAT, SOD, and CP450, respectively. The treatment with A. crassiflora seeds and peel extracts alone inhibited lipid peroxidation by 27 and 22%, respectively without affecting the CP450 content. The pretreatment with the A. crassiflora extracts prevented the lipid peroxidation, the increase in GSH equivalents and the decrease in CAT activity caused by CCl4, but it had no effect on the CCl4-mediated changes in CP450 and b5 and SOD. These results show that A. crassiflora seeds and peel contain antioxidant activity in vivo that could be of potential therapeutic use.

Phenolic compounds and antioxidant activity in fermented rice (Oryza sativa) bran

This study investigated the content of total phenolic compounds and antioxidant activity in fermented rice bran in order to evaluate the effect of solid state fermentation on these properties. The process was performed with the fungus Rhizopus oryzae CTT 1217 in tray reactors at 30 °C for 120 hours. Samples of fermented rice bran were collected every 24 hours. Antioxidant property was evaluated by the diphenyl-1-picrylhydrazyl radical scavenging method and through the inhibition of enzymatic oxidation and lipid peroxidation of olive oil. The methanol extract of the biomass obtained at 96 hours of fermentation inactivated 50% of free radical in 15 minutes. The same extract reduced the peroxide value in the olive oil by 57% after 30 days of storage. The aqueous extract of the biomass obtained at 120 hours was the most efficient inhibitor of the darkening reaction catalyzed by peroxidase.

Antioxidant potential of barley extract in rats subjected to a high-fat diet

Antioxidants have the ability to neutralize free radicals produced in the body during lipid oxidation. The objective in this article was to study the effect of the barley extract on lipid oxidation in rats subjected to a high-fat diet. The experiment lasted 67 days. The animals were separated into three experimental groups: standard (P), high-fat diet group (L), and group with high-fat diet supplemented with barley extract (C). The feed intake of L and C groups was the lowest (p < 0.05). The treatments did not influence weight gain, organ weight, and the blood parameters measured. However, the levels of malondialdehyde present in the liver tissue were higher in the L group and lower in the P and C groups. Therefore, the results indicated an increased level of lipid peroxidation in the liver of rats subjected to high-fat diet, which was reduced by the consumption of barley.

In vitro and in vivo antioxidant activity of the pulp of Jatobá-do-cerrado

Abstract Oxygen metabolism in cells causes the production of free radicals, which produce damage, including changes in cell structure and function. Antioxidants are substances that, at low concentrations, slow down or prevent oxidation. Fruits and vegetables contribute to the dietary supply of these compounds. The flora of the Cerrado in Brazil has shown to have high levels of bioactive compounds. This study aimed to characterize the antioxidant activity of the pulp of jatobá-do-cerrado in vitro and in vivo.In vitro antioxidant activity of the aqueous, ethanol and aqueous acetone extracts was evaluated by the DPPH method. We determined total phenols by the Folin-Ciocalteu assay and tannins by the Folin-Denis method.In vivo antioxidant potential of the aqueous acetone extract was evaluated by the TBARS technique. The aqueous acetone extract had the highest antioxidant capacity, followed by the aqueous and ethanol extracts. The same pattern occurred in the extraction of phenols and in the extraction of tannins. In vivo administration of the aqueous acetone extract inhibited lipid peroxidation compared to the control group. The inhibition of peroxidation has increased by elevating the dosage concentration of the extracts, demonstrating a significant antioxidant potential in vivo as well as in vitro.

Blood lipid associations in 18 year-old men

The association of cigarette smoking, physical activity at work, and social class with total cholesterol and with high and low density lipoprotein cholesterol were examined in a random sample of 238 males, of 18 years of age, of Rosario, Argerntina. The mean (mg/dl) total serum cholesterol of the whole sample was 174.7, the high density lipoprotein cholesterol 52.8, and the low density lipoprotein cholesterol 121.5. Black tobacco consumers, evenly distributed by social class, had higher levels of total and low density lipoprotein cholesterol. Total cholesterol was higher in the high social class, differently from what smokers' distribution by social class, would lead one to expect. While a highly negative association was found between social class and physical activity at work, there were no significant diferences in lipoprotein levels between manual and non-manual workers. It is possible that the nutritional differences by social class still prevail over the smoking habit in their influence on the lipoprotein levels in these subjects.

Body mass index for predicting hyperglycemia and serum lipid changes in Brazilian adolescents

OBJECTIVE: To determine the best cut-offs of body mass index for identifying alterations of blood lipids and glucose in adolescents. METHODS: A probabilistic sample including 577 adolescent students aged 12-19 years in 2003 (210 males and 367 females) from state public schools in the city of Niterói, Southeastern Brazil, was studied. The Receiver Operating Characteristic curve was used to identify the best age-adjusted BMI cut-off for predicting high levels of serum total cholesterol (>150mg/dL), LDL-C (>100mg/dL), serum triglycerides (>100mg/dL), plasma glucose (>100mg/dL) and low levels of HDL-C (< 45mg/dL). Four references were used to calculate sensitivity and specificity of BMI cut-offs: one Brazilian, one international and two American. RESULTS: The most prevalent metabolic alterations (>50%) were: high total cholesterol and low HDL-C. BMI predicted high levels of triglycerides in males, high LDL-C in females, and high total cholesterol and the occurrence of three or more metabolic alterations in both males and females (areas under the curve range: 0.59 to 0.67), with low sensitivity (57%-66%) and low specificity (58%-66%). The best BMI cut-offs for this sample (20.3 kg/m² to 21.0 kg/m²) were lower than those proposed in the references studied. CONCLUSIONS: Although BMI values lower than the International cut-offs were better predictor of some metabolic abnormalities in Brazilian adolescents, overall BMI is not a good predictor of these abnormalities in this population.