Oxidative DNA damage is prevented by extracts of olive oil, hydroxytyrosol, and other olive phenolic compounds in human blood mononuclear cells and HL60 cells

Our aim in this study was to provide further support to the hypothesis that phenolic compounds may play an important role in the anticarcinogenic properties of olive oil. We measured the effect of olive oil phenols on hydrogen peroxide (H(2)O(2))-induced DNA damage in human peripheral blood mononuclear cells (PBMC) and promyelocytic leukemia cells (HL60) using single-cell gel electrophoresis (comet assay). Hydroxytyrosol [3,4-dyhydroxyphenyl-ethanol (3,4-DHPEA)] and a complex mixture of phenols extracted from both virgin olive oil (OO-PE) and olive mill wastewater (WW-PE) reduced the DNA damage at concentrations as low as 1 micromol/L when coincubated in the medium with H(2)O(2) (40 micromol/L). At 10 micromol/L 3,4-DHPEA, the protection was 93% in HL60 and 89% in PBMC. A similar protective activity was also shown by the dialdehydic form of elenoic acid linked to hydroxytyrosol (3,4-DHPEA-EDA) on both kinds of cells. Other purified compounds such as isomer of oleuropein aglycon (3,4-DHPEA-EA), oleuropein, tyrosol, [p-hydroxyphenyl-ethanol (p-HPEA)] the dialdehydic form of elenoic acid linked to tyrosol, caffeic acid, and verbascoside also protected the cells against H(2)O(2)-induced DNA damage although with a lower efficacy (range of protection, 25-75%). On the other hand, when tested in a model system in which the oxidative stress was induced by phorbole 12-myristate 13-acetate-activated monocytes, p-HPEA was more effective than 3,4-DHPEA in preventing the oxidative DNA damage. Overall, these results suggest that OO-PE and WW-PE may efficiently prevent the initiation step of carcinogenesis in vivo, because the concentrations effective against the oxidative DNA damage could be easily reached with normal intake of olive oil.     

Hydroxytyrosol protects against oxidative DNA damage in human breast cells

Over recent years, several studies have related olive oil ingestion to a low incidence of several diseases, including breast cancer. Hydroxytyrosol and tyrosol are two of the major phenols present in virgin olive oils. Despite the fact that they have been linked to cancer prevention, there is no evidence that clarifies their effect in human breast tumor and non-tumor cells. In the present work, we present hydroxytyrosol and tyrosol's effects in human breast cell lines. Our results show that hydroxytyrosol acts as a more efficient free radical scavenger than tyrosol, but both fail to affect cell proliferation rates, cell cycle profile or cell apoptosis in human mammary epithelial cells (MCF10A) or breast cancer cells (MDA-MB-231 and MCF7). We found that hydroxytyrosol decreases the intracellular reactive oxygen species (ROS) level in MCF10A cells but not in MCF7 or MDA-MB-231 cells while very high amounts of tyrosol is needed to decrease the ROS level in MCF10A cells. Interestingly, hydroxytyrosol prevents oxidative DNA damage in the three breast cell lines. Therefore, our data suggest that simple phenol hydroxytyrosol could contribute to a lower incidence of breast cancer in populations that consume virgin olive oil due to its antioxidant activity and its protection against oxidative DNA damage in mammary cells.     

Is dopamine behind the health benefits of red wine?

Background The contribution of biologically active non-nutrient chemicals to the health benefits of the Mediterranean diet is controversial because of their low dietary concentrations. Hydroxytyrosol is a dopamine metabolite, and also a very active naturally occurring phenol compound in olive oil. Aim of the study To examine the disposition of hydroxytyrosol in humans, given that we discovered its presence in red wine in the frame of the study. Methods The pharmacokinetics of hydroxytyrosol from two clinical trials, designed to assess the short-term and postprandial effects of moderate doses of wine and olive oil in healthy volunteers, were compared. Results Despite a five-fold difference in the doses of hydroxytyrosol administered (0.35 mg for red wine and 1.7 mg for olive oil), urinary recoveries of hydroxytyrosol were higher after red wine administration. An interaction between ethanol and dopamine after red wine ingestion leading to the formation of hydroxytyrosol was observed. Conclusions Biological effects after red wine ingestion should be re-examined on the basis of combined hydroxytyrosol concentrations from red wine and dopamine turnover.     

Virgin olive oil polyphenol hydroxytyrosol acetate inhibits in vitro platelet aggregation in human whole blood: comparison with hydroxytyrosol and acetylsalicylic acid

Hydroxytyrosol acetate (HT-AC) is a polyphenol present in virgin olive oil (VOO) at a proportion similar to hydroxytyrosol (HT) (160-479 micromol/kg oil). The present study was designed to measure the in vitro platelet antiaggregating activity of HT-AC in human whole blood, and compare this effect with that of HT and acetylsalicylic acid (ASA). The experiments were designed according to the standard procedure to investigate the activity of ASA. HT-AC and HT inhibited platelet aggregation induced by ADP, collagen or arachidonic acid in both whole blood and platelet-rich plasma (PRP). ASA and HT-AC had a greater effect in whole blood than in PRP when ADP or collagen was used as inducer. ASA and HT-AC had a greater effect in PRP+leucocytes than in PRP alone. All three compounds inhibited platelet thromboxane B2 and leucocyte 6-keto-prostaglandin F1alpha (6-keto-PF1 alpha) production. The thromboxane/6-keto-PGF1alpha inhibition ratio (as an indirect index of the prostanoid equilibrium) was 10.8 (SE 1) for HT-AC, 1.0 (SE 0.1) for HT and 3.3 (SE 0.2) for ASA. All three compounds stimulated nitric oxide production, although HT was a weaker effect. In our experiments only concentrations higher than 500 microm (HT) or 1 mm (HT-AC and ASA) inhibited 3-nitrotyrosine production. All three compounds inhibited the production of TNFalpha by leucocytes, with no significant differences between them. In quantitative terms HT-AC showed a greater antiplatelet aggregating activity than HT and a similar activity to that of ASA. This effect involved a decrease in platelet thromboxane synthesis and an increase in leucocyte nitric oxide production.     

NaAsO2对L-02肝细胞氧化应激性损伤及SOD1、AUF1表达影响

目的 观察不同剂量亚砷酸钠（NaAsO2）对L-02肝细胞氧化应激性损伤作用及超氧化物歧化酶1（SOD1）、AU 碱基富集元件RNA 结合因子1（AUF1）表达影响。方法 用0、10、20、40μmol/L NaAsO2分别处理L-02肝细胞24小时，化学比色法检测谷胱甘肽巯基转移酶（GST）、γ-谷氨酰转肽酶（γ-GT）活力及总胆汁酸（TBA）含量和SOD1、谷胱甘肽过氧化物酶（GPx）活性；荧光探针2,7-二氯二氢荧光素二乙酸酯检测细胞内活性氧族（ROS）相对荧光密度；实时荧光定量PCR和Western Blotting分别检测SOD1和AUF1转录和蛋白表达。结果 （1）与对照组比较，20、40μmol/L NaAsO2组GST活性和TBA含量均升高（P<0.05）；10、20、40μmol/L NaAsO2组γ-GT活性也升高（P<0.05）。（2）与对照组比较，20、40 μmol/L NaAsO2组SOD1活性均下降（P<0.05）；GPx活性仅在10μmol/L升高（P<0.05）；细胞内ROS先降低后升高（P<0.05）。（3）与对照组比较，20和40μmol/L NaAsO2组AUF1和SOD1 mRNA表达均升高（P<0.05），AUF1蛋白表达先升高后降低（P<0.05）；10、20μmol/L NaAsO2组SOD1蛋白表达升高（P<0.05），但40μmol/L NaAsO2组SOD1蛋白表达有降低趋势。结论 NaAsO2对L-02肝细胞产生氧化应激性损伤，其机制可能是NaAsO2通过降低AUF1的蛋白表达降低，从转录后调控降低了SOD1 mRNA的稳定性而使其蛋白表达和酶活力降低。     

不同营养素配方饲料对小鼠抗氧化能力的影响

目的：观察3种含有不同量营养元素的饲料（NRC、XYZ、E100）对小鼠抗氧化能力的影响。方法：采用不同配方饲料预先饲养小鼠8周后，给小鼠一定处置，造成氧化损伤，测定脑、心、肝、肾4种组织中脂质过氧化物（TBARS）含量、羰基蛋白含量、谷胱苷肽过氧化物酶（GPX）的活力，CGPx、PHGPx、MnSOD的mRNA表达等指标的变化。结果：以普通饲料NRC饲养的小鼠经处置后，4种组织中的脂质过氧化物、羰基蛋白含量均有不同程度的上升，GPx酶活力下降，CGPx、PHGPx的mRNA表达下调，心与肝的MnSOD的mRNA表达上调，XYZ配方能较好地预防组织氧化损伤，E100的作用较差。结论：精神压力能够引起氧化损伤，不同营养素配方饲料对各项氧化损伤指标的影响不同。     

Oxidative stress and genotoxic responses to resin acids in Mediterranean mussels

This study represents the first attempt to investigate the genotoxic effects and oxidative stress of resin acids in Mediterranean mussels (Mytilus galloprovincialis Lmk). Mussels were exposed to 2.7 microM abietic acid (AA) and dehydroabietic acid (DHAA) for 6, 12, 18, and 24h. Gill and hepatopancreas conjugation activity, antioxidant defense system, lipid peroxidation (LPO), and DNA damage were determined as reduced glutathione (GSH), glutathione S-transferase (GST) activity, glutathione peroxidase (GPx) activity, catalase (CAT) activity, LPO, and DNA strand breaks. AA caused significant GST inhibition in mussel gills at 12, 18, and 24h. Activity of the antioxidant enzymes, namely, GPx and CAT, was inhibited at 24 and 18 h, respectively, in mussel gills. A significant increase in gill LPO was observed at 24h. The DNA integrity of mussel hepatopancreas significantly decreased after 12 and 24 h exposure to AA. A significant increase in LPO was observed after 6h exposure to DHAA, in either mussel gills or hepatopancreas. DNA integrity was significantly decreased in mussel hepatopancreas after 12 and 24 h exposure to DHAA. AA induced oxidative damage and genotoxicity in mussels, because it promoted increases in LPO in gills and DNA strand breaks in hepatopancreas. DHAA promoted oxidative damage and genotoxicity in mussels, as significant increases were observed in LPO in gills and hepatopancreas and in DNA strand breaks in hepatopancreas.     

Effects of fatty acids on skeletal muscle cell differentiation in vitro

Previous studies have shown stimulatory effects of linoleic acid (LA, C18:2) on differentiation of rat muscle cells in culture (Allen et al. 1985), but there appears to be little investigation of the effects of other fatty acids. The present study therefore compared the effects of different fatty acids on muscle cell differentiation in vitro. L6 myoblasts were cultured (Dulbecco's Modified Eagles Medium + 10 % fetal calf serum) in six-well plates until 80 % confluent (day 0). Cells were then either harvested or the medium switched to differentiation medium (Dulbecco's Modified Eagles Medium+2 % horse serum), supplemented with fatty acid or drug treatments. Cells were harvested on days 0-5 and assayed for creatine kinase (CK), protein and DNA contents, to give a measure of differentiation (CK/DNA). Initial studies indicated a stimulatory effect of the cis9,trans11 (c9,t11) isomer of conjugated linoleic acid (CLA) relative to control. By contrast, the trans10,cis12 (t10,c12) isomer of CLA inhibited differentiation. Further experiments indicated that inhibition of differentiation by the t10,c12 CLA isomer was dose-dependent (up to 200 microm) and may be via increased cell proliferation. LA and c9,t11 CLA stimulated differentiation at low concentrations (up to 50 microm), but inhibited differentiation at high concentrations (200 microm). In contrast, oleic acid stimulated differentiation at all concentrations, whereas the saturated fatty acid, palmitic acid, had no effect. The mechanism appeared not to involve either peroxisome proliferator-activated receptors alpha or gamma. The data suggest that only unsaturated fatty acids have an effect and the presence or absence of a cis-9 double bond may be important.     

Daily consumption of a high-phenol extra-virgin olive oil reduces oxidative DNA damage in postmenopausal women

Extra-virgin olive oils (EVOO), high in phenolic compounds with antioxidant properties, could be partly responsible for the lower mortality and incidence of cancer and CVD in the Mediterranean region. The present study aims to measure oxidative DNA damage in healthy human subjects consuming olive oils with different concentrations of natural phenols. A randomised cross-over trial of high-phenol EVOO (high-EVOO; 592 mg total phenols/kg) v. low-phenol EVOO (low-EVOO; 147 mg/kg) was conducted in ten postmenopausal women in Florence. Subjects were asked to substitute all types of fat and oils habitually consumed with the study oil (50 g/d) for 8 weeks in each period. Oxidative DNA damage was measured by the comet assay in peripheral blood lymphocytes, collected at each visit during the study period. Urine samples over 24 h were collected to measure the excretion of the olive oil phenols. The average of the four measurements of oxidative DNA damage during treatment with high-EVOO was 30 % lower than the average during the low-EVOO treatment (P=0.02). Urinary excretion of hydroxytyrosol and its metabolite homovanillyl alcohol were significantly increased in subjects consuming high-EVOO. Despite the small sample size, the present study showed a reduction of DNA damage by consumption of an EVOO rich in phenols, particularly hydroxytyrosol.     

Early detection of lung cancer potential among Egyptian wood workers

Wood dust is known to be a human carcinogen, with a considerable risk of lung cancer. The increased cancer risk is likely induced through its genotoxic effects resulting from oxidative DNA damage. This study aimed at assessing the genotoxicity of wood dust and demonstrating the role of sputum PCR as a screening tool for early prediction of lung cancer among wood workers. The study was carried out in the carpentry section of a modernized factory involved with the manufacture of wooden furniture in Greater Cairo, Egypt. Environmental assessment of respirable wood dust concentrations was done. Frequency of chromosomal aberrations (CA%) and sister chromatid exchanges (SCE%) in peripheral blood lymphocytes (PBL) was assessed and comet assays were performed in samples from among the study population (n = 86). Levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymes were measured. The polymerase chain reaction (PCR) was used to study hypermethylation of p16 and ?or O⁶-methylguanine-DNA methyltransferase (MGMT) gene promoters in sputum DNA. The concentrations of respirable wood dust exceeded the Egyptian and international permissible limits with highest levels generated by sawing operations. Laboratory investigations revealed statistically significantly higher frequencies of CA and SCE as well as increased comet tail length associated with significant decrement in the levels of SOD and GPx among exposed group. A statistically significant elevation in the extent of hypermethylation was detected for the p16 and MGMT gene promoters in the sputum DNA of studied wood workers. The study results support the conclusion that prolonged unprotected occupational exposure to wood dust is associated with possible genotoxicity and oxidative stress that might raise the risk for carcinogenesis including lung cancer.     

The effects of orally administered linoleic acid and its autoxidation products on intestinal mucosa in rat

Linoleic acid and its autoxidation products, hydroperoxides and their secondary products, were orally administered to rats (350 mg each/rat). Hemorrhage was seen in the alimentary canal at 6 h after the dose of hydroperoxides. To examine their toxicities on intestinal mucosa, the activities of mucous enzymes (sucrase, maltase, and alkaline phosphatase) were measured. Hydroperoxides and their secondary products decreased the enzyme activities in jejunum at 6 h after the doses and increased them in both jejunum and ileum at 15 h, as compared to linoleic acid or saline solution. The decrease of enzyme activity was marked in the hydroperoxide group and the increase was marked in the secondary product group. Then, in in vitro experiments, the effects of autoxidation products on these enzymes were determined. Autoxidation products inactivated only alkaline phosphatase. Thus, the results in vivo disagreed with those in vitro. It was assumed that autoxidation products orally administered attacked a membrane of intestinal microvilli whereas in vitro they directly affected the enzymes.     

Olive oil phenols are absorbed in humans

Animal and in vitro studies suggest that olive oil phenols are effective antioxidants. The most abundant phenols in olive oil are the nonpolar oleuropein- and ligstroside-aglycones and the polar hydroxytyrosol and tyrosol. The aim of this study was to gain more insight into the metabolism of those phenols in humans. We measured their absorption in eight healthy ileostomy subjects. We also measured urinary excretion in the ileostomy subjects and in 12 volunteers with a colon. Subjects consumed three different supplements containing 100 mg of olive oil phenols on separate days in random order. Ileostomy subjects consumed a supplement with mainly nonpolar phenols, one with mainly polar phenols and one with the parent compound oleuropein-glycoside. Subjects with a colon consumed a supplement without phenols (placebo) instead of the supplement with oleuropein-glycoside. Ileostomy effluent and urine were collected for 24 h after supplement intake. Tyrosol and hydroxytyrosol concentrations were low (< 4 mol/100 mol of intake) in the ileostomy effluent, and no aglycones were detected. We estimated that the apparent absorption of phenols was at least 55-66% of the ingested dose. Absorption was confirmed by the excretion of tyrosol and hydroxytyrosol in urine. In ileostomy subjects, 12 mol/100 mol and in subjects with a colon, 6 mol/100 mol of the phenols from the nonpolar supplement were recovered in urine as tyrosol or hydroxytyrosol. In both subject groups, 5--6 mol/100 mol of the phenols was recovered from the polar supplement. When ileostomy subjects were given oleuropein-glycoside, 16 mol/100 mol was recovered in 24-h urine, mainly in the form of hydroxytyrosol. Thus, humans absorb a large part of ingested olive oil phenols and absorbed olive oil phenols are extensively modified in the body.     

Absorption and metabolism of caffeic acid and chlorogenic acid in the small intestine of rats

The absorption and metabolism in the small intestine of chlorogenic acid (5-O-caffeoylquinic acid), the main phenolic acid in the human diet, and of caffeic acid were studied in rats in order to determine whether chlorogenic acid is directly absorbed or hydrolysed in the small intestine. Chlorogenic and caffeic acids were perfused into a segment of ileum plus jejunum during 45 min (50 microm, 0.75 ml/min) using an in situ intestinal perfusion rat model with cannulation of the biliary duct, and were quantified together with their metabolites in perfusion effluent, bile and plasma. The net absorption (influent flux minus effluent flux of phenolic acids and their metabolites) accounted for 19.5 % and 8 % of the perfused caffeic and chlorogenic acids, respectively. A minor fraction of the perfused caffeic acid was metabolized in the intestinal wall and secreted back into the gut lumen in the form of ferulic acid (0.5 % of the perfused flux). Part of the chlorogenic acid (1.2 % of the perfused flux) was recovered in the gut effluent as caffeic acid, showing the presence of trace esterase activity in the gut mucosa. No chlorogenic acid was detected in either plasma or bile, and only low amounts of phenolic acids (less than 0.4 %) were secreted in the bile. The present results show that chlorogenic acid is absorbed and hydrolysed in the small intestine. In contrast to numerous flavonoids, absorbed phenolic acids are poorly excreted in the bile or gut lumen. Their bioavailability therefore appears to be governed largely by their uptake into the gut mucosa.     

Detection of DNA damage by alkaline single cell gel electrophoresis in 2,4-dichlorophenoxyacetic-acid- and butachlor-exposed erythrocytes of Clarias batrachus

The alkaline single cell gel electrophoresis, also known as comet assay, is a rapid, simple and sensitive technique for measuring DNA strand breaks in individual cells. The present study was undertaken to evaluate the genotoxic potential of two widely used herbicides; 2,4-dichlorophenoxyacetic acid (2,4-D) and 2-chloro-2,6-diethyl-N-(butoxymethyl) acetanilide (butachlor) in erythrocytes of freshwater catfish, Clarias batrachus. Fish were exposed by medium treatment with three sub-lethal concentrations of 2,4-D (25, 50, and 75ppm) and butachlor (1, 2, and 2.5ppm) and alkaline comet assay was performed on nucleated erythrocytes after 48, 72, and 96h. The amount of DNA damage in cells was estimated from comet tail length as the extent of migration of the genetic material. A significant increase in comet tail length indicating DNA damage was observed at all concentrations of both the herbicides compared with control (P<0.05). The mean comet tail length showed a concentration-related and time-dependent increase as the maximum tail length recorded at highest concentration and longer duration of 2,4-D (9.59microm) and butachlor (9.28microm). This study confirmed that the comet assay applied on the fish erythrocyte is a useful tool in determining potential genotoxicity of water pollutants and might be appropriate as a part of a monitoring program.     

Oxidative stress responses in different organs of Jenynsia multidentata exposed to endosulfan

We evaluate antioxidant responses of Jenynsia multidentata experimentally exposed to sublethal concentrations of endosulfan (EDS). The main goal was to determine differences in the response between different organs to assess which one was more severely affected. Thus, we exposed females of J. multidentata to EDS during 24h, measuring the activity of GST, GR, GPx, CAT and LPO in brain, gills, liver, intestine and muscle of both exposed fish and controls. GST activity was inhibited in gills, liver, intestine and muscle of exposed fish but was induced in brain. GR and GPx activities were increased in brain and gills at 0.014 and 0.288 microg L(-1), respectively. GPx activity was inhibited in liver and muscle at all studied concentrations whereas inhibition was observed in the intestine above 0.288 microg L(-1). Exposure to 1.4 microg L(-1) EDS caused CAT inhibition and increase of LPO levels in liver. LPO was also increased in brain at almost all concentrations tested. We find that the brain was the most sensitive organ to oxidative damage. Thus, J. multidentata could be used as a suitable bioindicator of exposure to EDS measuring activities of antioxidant enzymes in brain and liver as biomarkers.     

Oxidative damage induced in brains and livers of mice by landfill leachate

The effects of the Xingou municipal landfill leachate on levels of thiobarbituric acid reactive substances (TBARS) and the activities of Cu,Zn-superoxide dismutase (Cu,Zn-SOD), Se-dependent glutathione peroxidase (Se-dependent GPx), and catalase (CAT) were investigated in brains and livers of Kunming albino mice of both sexes, using chemical oxygen demand (COD(Cr)) as a measure of leachate concentration. The results show that leachate caused lipid peroxidation and change of antioxidative status in brains and livers of mice. There was a sex difference in the response of antioxidative status, and female mice were more sensitive than male mice. Exposure to leachate at all concentrations tested caused significant increases of TBARS levels in brains and livers from mice of both sexes. For brains, Cu,Zn-SOD and Se-dependent GPx activities were significantly increased at high concentration (COD(Cr) 240 mg/L) for male mice, but the activities of both antioxidative enzymes were significantly increased at low concentration (COD(Cr) 60 mg/L) and decreased at high concentration (COD(Cr) 240 mg/L) for female mice; CAT activities remained unchanged for male mice and were significantly decreased for female mice at high concentration (COD(Cr) 240 mg/L). For livers, Cu,Zn-SOD and Se-dependent GPx activities were significantly increased at high concentrations (COD(Cr) 120 and 240 mg/L) for male mice, but the activities of both antioxidative enzymes were significantly increased at low concentration (COD(Cr) 30 or 60 mg/L) and decreased at high concentration (COD(Cr) 240 mg/L) for female mice; CAT activities were significantly increased for male mice at all concentrations tested and decreased for female mice at high concentrations (COD(Cr) 120 and 240 mg/L). These results suggest that leachate exposure can cause oxidative damage on brains and livers of mice. The results also suggest that leachate might induce toxicity in mammals by the free-radical-damage mechanism.     

Tyrosol and hydroxytyrosol are absorbed from moderate and sustained doses of virgin olive oil in humans

OBJECTIVE: To investigate the absorption of tyrosol and hydroxytyrosol from moderate and sustained doses of virgin olive oil consumption. The study also aimed to investigate whether these phenolic compounds could be used as biomarkers of virgin olive oil intake. DESIGN AND INTERVENTIONS: Ingestion of a single dose of virgin olive oil (50 ml). Thereafter, for a week, participants followed their usual diet which included 25 ml/day of the same virgin olive oil as the source of raw fat. SETTING: Unitat de Recerca en Farmacologia. Institut Municipal d'Investigació Mèdica (IMIM). SUBJECTS: Seven healthy volunteers. RESULTS: An increase in 24 h urine of tyrosol and hydroxytyrosol, after both a single-dose ingestion (50 ml) and short-term consumption (one week, 25 ml/day) of virgin olive oil (P<0.05) was observed. Urinary recoveries for tyrosol were similar after a single dose and after sustained doses of virgin olive oil. Mean recovery values for hydroxytyrosol after sustained doses were 1.5-fold those obtained after a single 50 ml dose. CONCLUSIONS: Tyrosol and hydroxytyrosol are absorbed from realistic doses of virgin olive oil. With regard to the dose-effect relationship, 24 h urinary tyrosol seems to be a better biomarker of sustained and moderate doses of virgin olive oil consumption than hydroxytyrosol.     

Personal exposure to ultrafine particles and oxidative DNA damage

Exposure to ultrafine particles (UFPs) from vehicle exhaust has been related to risk of cardiovascular and pulmonary disease and cancer, even though exposure assessment is difficult. We studied personal exposure in terms of number concentrations of UFPs in the breathing zone, using portable instruments in six 18-hr periods in 15 healthy nonsmoking subjects. Exposure contrasts of outdoor pollution were achieved by bicycling in traffic for 5 days and in the laboratory for 1 day. Oxidative DNA damage was assessed as strand breaks and oxidized purines in mononuclear cells isolated from venous blood the morning after exposure measurement. Cumulated outdoor and cumulated indoor exposures to UFPs each were independent significant predictors of the level of purine oxidation in DNA but not of strand breaks. Ambient air concentrations of particulate matter with an aerodynamic diameter of < or = 10 microm (PM10), nitrous oxide, nitrogen dioxide, carbon monoxide, and/or number concentration of UFPs at urban background or busy street monitoring stations was not a significant predictor of DNA damage, although personal UFP exposure was correlated with urban background concentrations of CO and NO2, particularly during bicycling in traffic. The results indicate that biologic effects of UFPs occur at modest exposure, such as that occurring in traffic, which supports the relationship of UFPs and the adverse health effects of air pollution.     

Caffeic Acid Modulates Processes Associated with Intestinal Inflammation

Caffeic acid is one of the most abundant hydroxycinnamic acids in fruits, vegetables, and beverages. This phenolic compound reaches relevant concentrations in the colon (up to 126 µM) where it could come into contact with the intestinal cells and exert its anti-inflammatory effects. The aim of this investigation was to study the capacity of caffeic acid, at plausible concentrations from an in vivo point of view, to modulate mechanisms related to intestinal inflammation. Consequently, we tested the effects of caffeic acid (50–10 µM) on cyclooxygenase (COX)-2 expression and prostaglandin (PG)E₂, cytokines, and chemokines (IL-8, monocyte chemoattractant protein-1 -MCP-1-, and IL-6) biosynthesis in IL-1β-treated human myofibroblasts of the colon, CCD-18Co. Furthermore, the capacity of caffeic acid to inhibit the angiotensin-converting enzyme (ACE) activity, to hinder advanced glycation end product (AGE) formation, as well as its antioxidant, reducing, and chelating activity were also investigated. Our results showed that (i) caffeic acid targets COX-2 and its product PGE₂ as well as the biosynthesis of IL-8 in the IL-1β-treated cells and (ii) inhibits AGE formation, which could be related to (iii) the high chelating activity exerted. Low anti-ACE, antioxidant, and reducing capacity of caffeic acid was also observed. These effects of caffeic acid expands our knowledge on anti-inflammatory mechanisms against intestinal inflammation.