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Biomedical subjects

Henrik E Poulsen

Publications and source records attributed to Henrik E Poulsen.

At least 19 recordsLinked to original sources
PubMed2007

Moderate consumption of olive oil by healthy European men reduces systolic blood pressure in non-Mediterranean participants.

We evaluated the effects of a moderate consumption of olive oil on lipid profile, BMI, and blood pressure (BP) in a group of 160 healthy men from non-Mediterranean regions [Northern Europe (n = 50; Finland and Denmark) and Central Europe (n = 60; Germany)] and Mediterranean regions [Southern Europe (n = 45; Italy and Spain)]. The study was a randomized, cross-over trial with 3 intervention periods of 3 wk and 2 wash-out periods of 2 wk. At the intervention periods, 3 similar olive oils (25 mL/d), differing only in their phenolic concentration, were administered to the healthy volunteers. Plasma oleic acid levels increased 2-3% (P < 0.05) in men from populations with lower habitual olive oil intakes (Northern and Central Europe). General linear models showed that the administration of the sequence of the 3 olive oils was responsible for a 3% decrease in systolic BP (SBP) (P < 0.05), but not in diastolic BP, in the non-Mediterranean subjects. Multivariate analysis indicated that the lipid profile did not change in either Mediterranean or non-Mediterranean men due to the olive oil intervention. The results of this study suggest that a moderate consumption of olive oil may be used as an effective tool to reduce SBP of healthy men who do not typically consume a Mediterranean diet. However, additional longer trials are necessary for confirmation.

Adult↗
PubMed2006

Effect of olive oils on biomarkers of oxidative DNA stress in Northern and Southern Europeans.

High consumption of olive oil in the Mediterranean diet has been suggested to protect DNA against oxidative damage and to reduce cancer incidence. We investigated the impact of the phenolic compounds in olive oil, and the oil proper, on DNA and RNA oxidation in North, Central, and South European populations. In a multicenter, double-blind, randomized, controlled crossover intervention trial, the effect of olive oil phenolic content on urinary oxidation products of guanine (8-oxo-guanine, 8-oxo-guanosine and 8-oxo-deoxyguanosine) was investigated. Twenty-five milliliters of three olive oils with low, medium, and high phenolic content were administered to healthy males (n=182) daily for 3 wk. At study baseline the urinary excretion of 8-oxo-guanosine (RNA oxidation) and 8-oxo-deoxyguanosine (DNA oxidation) was higher in the Northern regions of Europe compared with Central and Southern European regions (P=0.035). Urinary excretion of the 8 hydroxylated forms of guanine, guanosine, deoxyguanosine and their nonoxidized forms were not different when comparing olive oils with low, medium, and high phenolic content given for 2 wk. Testing the effect of oil from urinary 8-oxo-deoxyguanosine changes from baseline to post-treatment showed a reduction of DNA oxidation by 13% (P=0.008). These findings support the idea that ingestion of olive oil is beneficial and can reduce the rate of oxidation of DNA. This effect is not due to the phenolic content in the olive oil. The higher DNA and RNA oxidation in Northern European regions compared with that in Central and Southern regions supports the contention that olive oil consumption may explain some of the North-South differences in cancer incidences in Europe.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2006

The effect of polyphenols in olive oil on heart disease risk factors: a randomized trial.

BACKGROUND: Virgin olive oils are richer in phenolic content than refined olive oil. Small, randomized, crossover, controlled trials on the antioxidant effect of phenolic compounds from real-life daily doses of olive oil in humans have yielded conflicting results. Little information is available on the effect of the phenolic compounds of olive oil on plasma lipid levels. No international study with a large sample size has been done. OBJECTIVE: To evaluate whether the phenolic content of olive oil further benefits plasma lipid levels and lipid oxidative damage compared with monounsaturated acid content. DESIGN: Randomized, crossover, controlled trial. SETTING: 6 research centers from 5 European countries. PARTICIPANTS: 200 healthy male volunteers. MEASUREMENTS: Glucose levels, plasma lipid levels, oxidative damage to lipid levels, and endogenous and exogenous antioxidants at baseline and before and after each intervention. INTERVENTION: In a crossover study, participants were randomly assigned to 3 sequences of daily administration of 25 mL of 3 olive oils. Olive oils had low (2.7 mg/kg of olive oil), medium (164 mg/kg), or high (366 mg/kg) phenolic content but were otherwise similar. Intervention periods were 3 weeks preceded by 2-week washout periods. RESULTS: A linear increase in high-density lipoprotein (HDL) cholesterol levels was observed for low-, medium-, and high-polyphenol olive oil: mean change, 0.025 mmol/L (95% CI, 0.003 to 0.05 mmol/L), 0.032 mmol/L (CI, 0.005 to 0.05 mmol/L), and 0.045 mmol/L (CI, 0.02 to 0.06 mmol/L), respectively. Total cholesterol-HDL cholesterol ratio decreased linearly with the phenolic content of the olive oil. Triglyceride levels decreased by an average of 0.05 mmol/L for all olive oils. Oxidative stress markers decreased linearly with increasing phenolic content. Mean changes for oxidized low-density lipoprotein levels were 1.21 U/L (CI, -0.8 to 3.6 U/L), -1.48 U/L (-3.6 to 0.6 U/L), and -3.21 U/L (-5.1 to -0.8 U/L) for the low-, medium-, and high-polyphenol olive oil, respectively. LIMITATIONS: The olive oil may have interacted with other dietary components, participants' dietary intake was self-reported, and the intervention periods were short. CONCLUSIONS: Olive oil is more than a monounsaturated fat. Its phenolic content can also provide benefits for plasma lipid levels and oxidative damage. International Standard Randomised Controlled Trial number: ISRCTN09220811.

Adult↗
PubMed2006

Effect of dietary virgin olive oil on urinary excretion of etheno-DNA adducts.

A significant protective effect against cancer and coronary heart disease has been attributed to the Mediterranean diet, in which olive oil is the main source of fat. Dietary antioxidants, as phenolic compounds from virgin olive oil, are candidates for reducing cancer risk by minimizing oxidatively derived DNA damage. Etheno-DNA adducts are formed as a result of oxidative stress and lipid peroxidation. To evaluate whether phenol-rich virgin olive oil influences urinary excretion of the etheno-DNA adducts epsilonAde, epsilondA, and epsilondC as markers of oxidative stress, a randomized, double-blinded, crossover trial with three intervention periods was conducted in 28 healthy men. Each intervention was of 3 weeks' duration and separated by 2-week washout periods. Twenty-five milliliters of similar olive oils, but with differences in their phenolic content (from 2.7 to 366 mg/kg), were supplied to each subject per day. The urinary excretion of the DNA adducts was assayed by LC-MS/MS in samples before and after consumption of high phenolic content olive oil (virgin). The 24-h excretion rate did not differ significantly between baseline and after virgin olive oil consumption: epsilonAde, 105.5 +/- 40.8 vs 116.4 +/- 53.4 pmol epsilonAde/24 h (p = 0.21); epsilondA, 37.9 +/- 24.8 vs 37.6 17 +/- 24.2 pmol epsilondA/24 h (p = 0.93); and epsilondC, 218.7 +/- 157.2 vs 193.5 +/- 64.7 pmol epsilondC/24 h (p = 0.37). Multiple regression analysis showed a significant association between etheno-DNA adduct excretion rate and the dietary intake of linoleic acid (C18:2, omega-6) in healthy men. Consumption of 25 ml per day of phenol-rich virgin olive oil for 3 weeks did not modify to a significant degree the urinary excretion of etheno-DNA adducts in 28 healthy volunteers.

Adult↗
PubMed2006

Oltipraz chemoprevention trial in Qidong, People's Republic of China: unaltered oxidative biomarkers.

Aflatoxin, which leads to formation of carcinogen-DNA adducts as well as oxidized DNA, is a well-known risk factor for development of hepatocellular carcinoma. The aim of the present study was to investigate if the chemopreventive agent oltipraz had an effect on DNA oxidation measured as oxidized guanine derivatives in urine among healthy individuals living in a region of China at high risk of exposure to aflatoxin and development of hepatocellular carcinoma. Two hundred thirty-three healthy residents of Qidong, PRC, were randomized to 8 weeks treatment with placebo, oltipraz 125 mg daily, or oltipraz 500 mg weekly, with a subsequent 8-week follow-up period. Urine samples were collected as overnight voids. Samples collected 4 weeks into the treatment period and 6 weeks into the follow-up period were analyzed for oxidized guanine derivatives with a HPLC-MS/MS method. A repeated-measures analysis of variance showed no significant differences between the randomization groups regarding changes in oxidized guanine derivatives. In the present double-blind, randomized, placebo-controlled trial performed among healthy individuals, oltipraz had no major effect on oxidative DNA damage. Mechanisms other than prevention of oxidative DNA damage may be of higher importance when oltipraz is used as a chemopreventive agent in humans.

Anticarcinogenic Agents↗
PubMed2006

Quantification of urinary etheno-DNA adducts by column-switching LC/APCI-MS/MS.

Lipid peroxidation induced etheno-DNA adducts are promutagenic and have been suggested to play a causal role in the development of human cancers. Therefore, human biomonitoring of etheno-DNA adducts in urine has been suggested as a potential marker for oxidative stress-related DNA damage. For quantitative determination, a column-switching LC/APCI-MS/MS method was developed for simultaneous analysis of epsilonAde, epsilondC, and epsilondA in human urine. Quantitative validation parameters (precision, within-day repeatability, and between-day reproducibility) yielded satisfactory results below 10%. Limit of quantification for epsilonAde, epsilondC, and epsilondA was 5.3 fmol, 7.5 fmol, and 1.3 fmol on column, respectively. Mean urinary excretion rates of a six healthy volunteers were 45.8 pmol epsilonAde/24 h, 96.8 pmol epsilondC/24 h, and 18.1 pmol epsilondA/24 h. The demonstrated levels of performance suggest a future applicability of this method to studies of cancer and other diseases related to oxidative stress in humans. To our knowledge, this is the first method described that allows simultaneous determination of epsilonAde, epsilondC, and epsilondA in human urine samples.

Biomarkers↗
PubMed2005

Measurement of caffeine and five of the major metabolites in urine by high-performance liquid chromatography/tandem mass spectrometry.

Analysis of caffeine and its metabolites is of interest with respect to caffeine exposure, for kinetic and metabolism studies and for opportunistic in vivo estimation of drug metabolizing enzyme activity in humans and animals. For the latter, analysis is usually done by high-performance liquid chromatography (HPLC) with UV detection. However, this method is close to the detection limit for certain of the metabolites and requires very long chromatography, 30-60 min. We have developed a fast method for the quantification of caffeine and its metabolites 1-methylxanthine, 1-methyluric acid, 1,7-dimethyluric acid, 5-acetylamino-6-amino-3-methyluracil (AAMU) and 5-acetylamino-6-formylamino-3-methyluracil (AFMU) by HPLC tandem mass spectrometry (MS/MS) in urine that requires only its dilution with buffer and centrifugation before injection into the HPLC/MS/MS system. The chromatography lasts 7 min and is followed by 4.5 min for re-equilibration of the HPLC column, giving a total analysis time of 11.5 min. The method provides a great sensitivity improvement with detection limits for all analytes <or=25 nM in real samples. Also, the analysis provides much improvement in capacity to approximately 125 samples per 24 h. Intra- and inter-day coefficients of variation of a single analysis are <6.5% for all the analytes. The inter-day coefficient of variation of duplicate analyses is <4.8% for all analytes. The method is automated, including automated integration, and it is fast, robust and suitable for large-scale investigations in humans and animals.

Caffeine↗
PubMed2005

Oxidative DNA modifications.

Oxidative DNA modifications are frequent in mammalian DNA and have been suggested an important mechanism in carcinogenesis, diabetes and ageing. The foundations for this suggestion are: Evidence for the importance of oxidative DNA modifications in cancer development is: high levels of oxidative lesions in cancer tissue; highly conserved and specific DNA repair systems targeting oxidative lesions; high levels of oxidative DNA lesions in oxidative DNA repair knock-out animals; defective repair of oxidative lesions in cancer-prone progeria syndromes; reduced cancer incidence in populations with high dietary antioxidant intake; and increased oxidative stress to DNA in tobacco smokers. Conflicting evidence for a relation between oxidative stress to DNA and cancer is: disagreement about the true levels and occurrence of the oxidative lesions in vivo; failure to identify the localization of oxidative lesions in important genes, e.g. tumor suppressor and oncogenes; lack of evidence that the oxidative lesions induce mutations in vivo; no cancer development in animals knocked-out for specific DNA repair enzymes in spite of high tissue levels of oxidative lesions; and unchanged cancer rates after antioxidant interventions in large clinical controlled and randomized trials. The rate of DNA oxidation has been estimated from urinary excretion of repair products and it is evident that if these lesions were not repaired, a large part of DNA would be oxidized to a degree not compatible with living. The methodologies by which oxidative DNA modifications are measured cover a wide and different range, advantages and disadvantages will be presented. One particular problem is artificial oxidation, and methods to prevent such artifacts will be presented together with results from a large interlaboratory standardization program. The methodology by which the lesions can be measured is complicated and prone to artifacts during DNA isolation, digestion, derivatization and maybe even during the separation procedure proper prior to detection. A large effort from 20+ laboratories supported by a grant from the EU has reduced artifacts considerably and work towards interlaboratory standardization of the methodology is in progress. The presently agreed "normal" levels of the most frequent known lesion 8-oxodG is about 5 per million dG's in DNA. A comprehensive evaluation of the evidence, from chemistry to clinical and epidemiological trials, linking oxidative modifications to cancer will be given. Finally, an estimate of the quantitative role oxidative DNA modifications play among the multiplicity of other insults is given. While there is no question that all of these oxidative mechanisms do exist, quantitative data on their importance for the human situation do not exist. Prospective human studies that can provide such quantitative data on different mechanisms are underway.

Aging↗
PubMed2005

Urinary excretion of epsilondA is not predictive of cancer development: a prospective nested case-control study.

Human biomonitoring of the lipid peroxidation DNA modification 1,N6-ethenodeoxyadenosine (epsilondA) excreted into urine is thought to be a potential marker for oxidative stress-related DNA damage and human cancer. We have tested this hypothesis in a prospective, nested case-control study. During the years 1984-1989, 24-h urines were collected from 1956 men in the Kuopio Ischaemic Heart Disease (KIHD) Risk Factor Study. epsilondA concentrations were measured by LC-MS/MS in 24-h urine samples from 47 men with cancer diagnosed at follow up until 2001 and from 31 cancer free smoking-matched control subjects. Odds ratio for having higher than control median epsilon dA excretion rate and cancer, estimated by binary logistic regression, was 0.73 (95% CI 0.29-1.80, p = 0.49). In this study, the urinary excretion of epsilondA provides no additional prediction of cancer development in males after controlling for smoking.

Adult↗
PubMed2004

Sucrose and IQ induced mutations in rat colon by independent mechanism.

Sucrose-rich diets have repeatedly been observed to have co-carcinogenic actions in colon and liver of rats and to increase the number of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) induced aberrant crypt foci in rat colon. To investigate a possible interaction between sucrose and IQ on the genotoxicity in rat liver and colon, we gave Big Blue rats a diet containing sucrose (0%, 3.45% or 13.4% w/w) and/or IQ (70 ppm) for a period of 3 weeks. Sucrose and IQ increased the mutation frequency in the colon. The effect of combined treatments with IQ and sucrose on the mutation frequencies was additive indicating that sucrose and IQ act independently. This was supported by the mutation spectra where sucrose expands the background mutations in the colon, whereas IQ, in other studies, more specifically has induced G:C --> T:A transversions. In the liver IQ increased the mutation frequency, whereas addition of sucrose reduced the effect of IQ in a dose-dependent manner. The level of bulky DNA adducts in liver and colon was increased in animals exposed to either sucrose or IQ. In animals exposed to IQ, addition of sucrose had marginal effects on the level of bulky DNA adducts. Markers of oxidative damage and DNA repair were generally unaffected by the treatments. In conclusion, sucrose and IQ in the diet induced mutations in the colon by independent mechanisms, whereas an interaction was observed in liver leading to a decrease in mutations by the combined treatment.

Animals↗
PubMed2004

Quantification of 1,N6-etheno-2'-deoxyadenosine in human urine by column-switching LC/APCI-MS/MS.

1,N6-etheno-2'-deoxyadenosine (epsilondA) is one of several promutagenic DNA modifications arising from cellular oxidative metabolism. It is believed that these background DNA lesions may contribute to various diseases, such as cancer. Therefore, human biomonitoring of epsilondA in urine could be a potential marker for oxidative stress-related DNA damage. Existing methods for quantifying urinary epsilondA use 32P postlabeling. We have developed a nonradioactive, fast, and easier method based on column-switching liquid chromatography with atmospheric pressure chemical ionization tandem mass spectrometry (LC/APCI-MS/MS) in the positive mode. Differences in column temperatures were used to influence analyte retention and sample focusing. With multiple reaction monitoring (MRM) mode the afforded limit of detection was about 0.7 pM when starting with 3 ml of urine. The urinary excretion rates of epsilondA from 28 nonsmoking and 5 smoking men were 10.0-99.6 pmol/24 h, and did not correlate with body weight, age, or plasma vitamin C concentration. The 5 smokers excreted 30.5 +/-8.5 and the 28 nonsmokers excreted 38.6 +/- 2.4 pmol epsilondA per 24 h, p=.37 (mean +/- SEM). The demonstrated level of performance suggests the future applicability of this method to studies of cancer and other diseases related to oxidative stress in humans.

Chromatography, Liquid↗
PubMed2004

Oligonucleotides in human urine do not contain 8-oxo-7,8-dihydrodeoxyguanosine.

The promutagenic DNA modification 8-oxo-7,8-dihydrodeoxyguanosine is the most frequently used marker for oxidative stress to DNA. The unmodified base and nucleoside and the 8-hydroxylated guanine base and nucleoside are found in urine, the latter used as a global measure of oxidative stress to DNA. Nucleotide excision repair (NER) excises a 27- to 29-mer oligonucleotide with oxidative lesions, and if found in urine, it could be used as a measure of DNA repair in vivo. Enzymatic hydrolysis of human urines followed by HPLC-tandem mass spectrometry was not able to reveal oligonucleotides and/or mononucleotides with the 8-oxo-7,8-dihydrodeoxyguanosine modification. The recovery of a synthetic oligonucleotide with the modification was complete (95% confidence limits: 98-124%). These experiments show that oligonucleotides are excreted into urine, but that 8-oxo-7,8-dihydrodeoxyguanosine is found only as the mononucleoside and is not present in any significant amounts in oligonucleotides. We conclude that oligonucleotides are excreted into urine, and they do not contain oxidized lesions. Either NER products are degraded after excision or NER functions differently in vivo in humans compared with cellular systems.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2004

Are we sure we know how to measure 8-oxo-7,8-dihydroguanine in DNA from human cells?

The most commonly measured marker of oxidative DNA damage is 8-oxo-7,8-dihydroguanine (8-oxoGua) or its deoxyribonucleoside (8-oxodGuo). Published estimates of the concentration of 8-oxoGua/8-oxodGuo in DNA of normal human cells vary over a range of three orders of magnitude. Analysis by chromatographic methods (GC-MS, HPLC with electrochemical detection (ECD) or HPLC-MS/MS) is beset by the problem of adventitious oxidation of guanine during sample preparation. An alternative approach, based on the use of the DNA repair enzyme formamidopyrimidine DNA N-glycosylase (FPG) to make breaks in the DNA at sites of the oxidised base, gives much lower values. ESCODD, the European Standards Committee on Oxidative DNA Damage, has been testing the ability of different laboratories using a variety of methods to measure 8-oxoGua in standard samples of 8-oxodGuo, calf thymus DNA, pig liver, oligonucleotides, and HeLa cells, and in lymphocytes isolated from blood of volunteers. HPLC-ECD is capable of measuring 8-oxodGuo induced experimentally in calf thymus DNA or HeLa cells with high accuracy. However, there is no sign of consensus over the background level of this damage, suggesting that, even though standard extraction procedures were used, variable oxidation of Gua is still occurring. GC-MS failed to detect a dose response of induced 8-oxoGua and cannot be regarded as a reliable method for measuring low levels of damage. HPLC-MS/MS as yet has not proved capable of measuring low levels of oxidative DNA damage. FPG-based methods seem to be less prone to the artefact of additional oxidation. Although they can be used quantitatively, they require careful calibration and standardisation if they are to be used in human biomonitoring. The background level of DNA oxidation in normal human cells is likely to be around 0.3-4.2 8-oxoGua per 10(6) Gua. An effort should be made to develop alternative, validated methods for estimating oxidative DNA damage.

Animals↗
PubMed2004

Low CYP1A2 activity associated with testicular cancer.

The incidence rate of testicular cancer has increased during the last 50 years. An interplay between changing environmental factors and individual susceptibility, e.g. in foreign compound metabolizing enzymes, may have important influences on the risk of testicular cancer. The cytochrome P4501A2 (CYP1A2) enzyme and the bimodally expressed enzyme N-acetyltransferase2 (NAT2) metabolize many procarcinogens/carcinogens. The aim of this population-based case-control study was to investigate if CYP1A2 or NAT2 activity measured as a ratio of urinary metabolites of dietary caffeine is a risk factor in testicular cancer. 378 men participated (80 seminomas, 104 non-seminomas and 194 controls). The CYP1A2 activity was lower in the cases than in the controls [median and 30-70% percentiles: 4.7 (3.9-5.7) and 5.2 (4.4-6.4), respectively]. The subjects were classified in tertiles with low, medium or high CYP1A2 activity. A low CYP1A2 activity was associated with the highest risk of testicular cancer. Including all participants except men using drugs suspected to influence CYP1A2 activity (n = 15), medium and low activity conferred odds ratios (ORs) of 1.54 [confidence intervals of 95% (CI(95%)) 0.93-2.55] and 2.11; CI(95%) (1.23-3.62), respectively, of having testicular cancer. Excluding smokers (n = 157) the ORs of medium and low activity were 3.63; CI(95%) (1.53-8.60) and 4.70; CI(95%) (2.03-10.89), respectively. After further exclusion of cases that had received chemotherapy or radiation (n = 47), similar significant results were achieved. In the groups with the lowest CYP1A2 activity the ORs for seminoma and non-seminoma were 2.12; CI(95%) (0.93-4.81) and 2.10; CI(95%) (1.02-4.32). The phenotype of NAT2 was not associated with testicular cancer. In conclusion, we found no association of NAT2 phenotype to testicular cancer, whereas significant associations between CYP1A2 activity and testicular cancer were shown.

Adult↗
PubMed2004

Vitamin C supplementation decreases oxidative DNA damage in mononuclear blood cells of smokers.

BACKGROUND: Antioxidants, in particular vitamin C, have been suggested to decrease oxidative DNA damage. Such effects have been shown in mononuclear blood cells in the first few hours after ingestion, whereas studies of longer-term effects in well-nourished humans have been mainly negative. AIM: To investigate the antioxidant effect of vitamin C in terms of oxidative DNA damage measured by the comet assay and DNA repair measured by expression of OGG1 mRNA in blood cells of male smokers given 2 x 250 mg vitamin C daily as plain or slow release tablets combined with plain release vitamin E 2 x 91 mg, or placebo for 4 wk. RESULTS: This study showed a difference in DNA protective effects between a slow release and a plain release vitamin C formulation. Ingestion of slow release vitamin C formulation was associated with fewer endonuclease III and formamidopyrimidine DNA glycosylase sensitive sites measured by the comet assay in mononuclear blood cells obtained 4 h and 8 h after a single tablet and 4 wk after two tablets a day. Ingestion of the vitamin formulation with plain release only indicated a damage-reducing effect 4 h after intake of a single tablet, and the effect was more apparent on endonuclease III than formamidopyrimidine DNA glycosylase sites. Overall the slow release tablets of vitamin C formulation had a more pronounced and a sustained protective effect on base damage compared with the plain release tablets. Plasma vitamin E was unaltered in the first 12 h after ingestion of a single tablet, suggesting that the antioxidant effect was mediated by vitamin C. Differences in plasma vitamin C levels at steady state could not explain the difference between the two vitamin C formulations, whereas wider amplitudes of plasma vitamin C were seen after ingestion of plain release formulation compared to slow release formulation. Assessment of OGG1 mRNA levels by RT-PCR did not indicate increased expression of this DNA repair gene after 4 wk of vitamin supplementation. CONCLUSION: This study suggests that long-term vitamin C supplementation at high dose, i. e. 500 mg together with vitamin E in moderate dose, 182 mg, decreases the steady-state level of oxidative DNA damage in mononuclear blood cells of smokers.

Adult↗
PubMed2004

Measurement of the malondialdehyde-2'-deoxyguanosine adduct in human urine by immuno-extraction and liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry.

The major adduct of malondialdehyde with guanine, M(1)G, was measured in human urine from non-smoking healthy individuals. M1G is a mutagenic DNA lesion and a terminal product of lipid peroxidation in vivo that may be implicated in cancer related to lifestyle and diet. On the basis of a recently developed method for the quantification of M1G as an excreted deoxynucleoside using immuno-extraction purification, chemical NaBH4 reduction and liquid chromatography combined with atmospheric pressure chemical ionization tandem mass spectrometry, we demonstrate that the average 24 h excretion rate of M1G-dR is about 12 +/- 3.8 fmol kg(-1) (n = 5).

Adult↗
PubMed2004

Vitamin C pharmacokinetics of plain and slow release formulations in smokers.

BACKGROUND & AIMS: Combination of the antioxidants ascorbic acid in slow release formulation and alpha-tocopherol can retard the progression of atherosclerosis. In order to determine if differences in formulation could explain some of the different results in the intervention trials we determined selected pharmacokinetics for two different formulations of ascorbic acid together with alpha-tocopherol. METHODS: Single-blinded, randomised, placebo-controlled intervention study with 48 healthy men, aged 20-65 years, smoking > or = 5 cigarettes/day. Subjects received 250 mg plain release ascorbic acid and 91 mg plain release d-alpha-tocopheryl acetate, 250 mg slow release ascorbic acid and 91 mg plain release d-alpha-tocopheryl acetate or placebo twice daily for 4 weeks. A series of blood samples were collected after administration of the first dose and repeated after 4 weeks of supplementation. RESULTS: The fluctuation of ascorbic acid plasma concentrations decreased significantly (P = 0.003) after 4 weeks supplementation in the slow versus the plain release group. CONCLUSIONS: This study shows that there were pharmacokinetic differences between plain and slow release formulations of ascorbic acid. However, these effects are small and unlikely to be of significant clinical importance.

Adult↗