Biomedical subjects

Lester Packer

Publications and source records attributed to Lester Packer.

At least 37 records · Page 2Linked to original sources

PubMed2003

Induction of stress proteins and MMP-9 by 0.8 ppm of ozone in murine skin.

Ozone (O(3)) is among the most reactive environmental oxidant pollutants to which cutaneous tissues are exposed. O(3) exposure has been shown to induce antioxidant depletion as well as the oxidation of lipids and proteins within the outermost skin layer, the stratum corneum. However, relatively little is known regarding the potential effects of O(3) on the cellular constituents of the underlying skin epidermis and dermis. In the present study, hairless mice exposed for 6 h to 0.8 ppm O(3) showed increases in lipid peroxidation, as quantitated by increases in 4-hydroxynonenal-protein adducts. O(3) exposure caused an induction of the stress proteins HSP27 and heme oxygenase-1 (HO-1), starting at 6 h and increasing up to 18 h after O(3) exposure. This was accompanied by an increase in matrix metalloproteinase-9 (MMP-9) mRNA and activity levels, indicative of possible injurious-reparative processes. Collectively, our data demonstrate that skin exposure to O(3) not only affects antioxidant levels and oxidation markers in the outermost stratum corneum layer, but also induces cellular stress responses in the deeper cellular layers of the skin.

Animals↗

PubMed2003

HPLC analysis of vitamin E isoforms in human epidermis: correlation with minimal erythema dose and free radical scavenging activity.

The content and composition of different vitamin E isoforms was analyzed in normal human skin. Interestingly the epidermis contained 1% alpha-tocotrienol, 3% gamma-tocotrienol, 87% alpha-tocopherol, and 9% gamma-tocopherol. Although the levels of tocotrienol in human epidermis appear to be considerably lower than reported in the hairless mouse, the presence of significant amounts of tocotrienol levels leads to speculation about the physiological function of tocotrienols in skin. Besides antioxidant activity and photoprotection, tocotrienols may have skin barrier and growth-modulating properties. A good correlation was found for epidermal alpha-tocopherol (r = 0.7909, p <.0003), gamma-tocopherol (r = 0.556, p <.025), and the total vitamin E content (r = 0.831, p <.0001) with the free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging in epidermis, as assessed by electron paramagnetic resonance (EPR) spectroscopy. In human epidermis, alpha-tocopherol is quantitatively the most important vitamin E isoform present and comprises the bulk of first line free radical defense in the lipid compartment. Epidermal tocotrienol levels were not correlated with DPPH scavenging activity. The minimal erythema dose (MED), an individual measure for sun sensitivity and a crude indicator for skin cancer susceptibility, did not correlate with the epidermal content of the vitamin E isoforms. Hence it is concluded that vitamin E alone is not a determinant of individual photosensitivity in humans.

Chromans↗

PubMed2003

Topical alpha-tocotrienol supplementation inhibits lipid peroxidation but fails to mitigate increased transepidermal water loss after benzoyl peroxide treatment of human skin.

Benzoyl peroxide (BPO) is a commonly used drug in the treatment of acne vulgaris, but it induces unwanted side effects related to stratum corneum (SC) function. Since it has been recently shown to oxidize SC antioxidants, it was hypothesized that antioxidant supplementation may mitigate the BPO-induced SC changes. To test this, 11 subjects were selected to be topically supplemented with alpha-tocotrienol (5% w/vol) for 7 d on defined regions of the upper back, while the contralateral region was used for vehicle-only controls. Starting on day 8, all test sites were also treated with BPO (10%) for 7 d; the alpha-tocotrienol supplementation was continued throughout the study. A single dose of BPO depleted 93.2% of the total vitamin E. While continuing the BPO exposure for 7 d further depleted vitamin E in both vehicle-only and alpha-tocotrienol-treated sites, significantly more vitamin E remained in the alpha-tocotrienol-treated areas. Seven BPO applications increased lipid peroxidation. Alpha-tocotrienol supplementation significantly mitigated the BPO-induced lipid peroxidation. The transepidermal water loss was increased 1.9-fold by seven BPO applications, while there was no difference between alpha-tocotrienol treatment and controls. The data suggest that alpha-tocotrienol supplementation counteracts the lipid peroxidation but not the barrier perturbation in the SC induced by 10% BPO.

Administration, Topical↗

PubMed2003

Smoking and exposure to environmental tobacco smoke decrease some plasma antioxidants and increase gamma-tocopherol in vivo after adjustment for dietary antioxidant intakes.

BACKGROUND: Free radicals in cigarette smoke may cause oxidative damage to macromolecules, contributing to cardiovascular diseases and cancer. Decreased plasma antioxidant concentrations may indicate cigarette smoke-related oxidative stress. OBJECTIVE: We compared the effects on plasma antioxidant concentrations in cotinine-confirmed active and passive smokers with those in nonsmokers, independent of differences in dietary intakes and other covariates. DESIGN: Plasma samples from 83 smokers, 40 passive smokers, and 36 nonsmokers were analyzed for total ascorbic acid, alpha- and gamma-tocopherols, 5 carotenoids, retinol, and cotinine. Groups were compared by using analysis of variance with adjustment for sex, age, race, body mass index, alcohol intake, triacylglycerol concentration, fruit and vegetable intakes, and dietary antioxidants. RESULTS: After adjustment for dietary antioxidant intakes and other covariates, smokers and passive smokers had significantly lower plasma beta-carotene concentrations than did nonsmokers (0.15, 0.17, and 0.24 micro mol/L, respectively) and significantly higher gamma-tocopherol concentrations (7.8, 7.8, and 6.5 micro mol/L, respectively). Smokers had significantly lower plasma ascorbic acid and beta-cryptoxanthin concentrations than did nonsmokers and passive smokers (ascorbic acid: 43.6, 54.5, and 54.6 micro mol/L, respectively; beta-cryptoxanthin: 0.12, 0.16, and 0.16 micro mol/L, respectively) and significantly lower concentrations of lutein and zeaxanthin than did nonsmokers (0.33 compared with 0.41 micro mol/L). The P values for all the differences described above were < 0.05. No significant differences in plasma concentrations of alpha-tocopherol, alpha-carotene, total carotenoids, lycopene, or retinol were observed. CONCLUSIONS: These results indicate that cigarette smokers and nonsmokers exposed to cigarette smoke have a significantly lower plasma antioxidant status than do unexposed nonsmokers, independent of differences in dietary antioxidant intakes. Further research is required to explain why plasma gamma-tocopherol concentrations were significantly higher in smokers and passive smokers than in nonsmokers.

Adult↗

PubMed2003

Lycopene inhibits the growth of normal human prostate epithelial cells in vitro.

Lycopene has repeatedly been shown to inhibit the growth of human prostate cells in vitro. However, previous studies with lycopene have focused on cancer specimens, and it is still unclear whether this carotenoid affects the growth of normal human prostate cells as well. Therefore, we investigated the effects of lycopene on normal human prostate epithelial cells (PrEC) by treating them with synthetic all-E-lycopene (up to 5 micromol/L) and assessing proliferation via [3H]thymidine incorporation. The effects of lycopene on cell cycle progression were investigated via flow cytometry. To elucidate whether lycopene modulates cyclins involved in cell cycle progression, protein expressions of cyclins D1 and E were analyzed. The results show that lycopene significantly inhibited the growth of PrEC in a dose-dependent fashion. Flow cytometry revealed a significant cell cycle arrest in the G0/G1 phase. This effect was confirmed by inhibition of cyclin D1 protein expression, whereas cyclin E levels remained unchanged. The results demonstrate that lycopene inhibits growth of nonneoplastic PrEC in vitro. We hypothesize that lycopene might likewise inhibit the growth of prostatic epithelial cells in vivo. This might have an effect on prostate development and/or on enlargement of prostate tissue as found in benign prostate hyperplasia, a potential precursor of prostate cancer.

Antioxidants↗

PubMed2003

Vitamin C supplementation decreases oxidative stress biomarker f2-isoprostanes in plasma of nonsmokers exposed to environmental tobacco smoke.

Exposure to environmental tobacco smoke (ETS) has been linked to increased risk of lung cancer and cardiovascular diseases in nonsmokers. Current research suggests that some of these diseases are associated with elevated oxidative stress. We investigated the effect of antioxidant (AO) intervention on the lipid peroxidation biomarker F2-isoprostanes (F2-IsoPs), an index of oxidative stress, in plasma of nonsmokers exposed to ETS (passive smokers). We measured free F2-IsoP concentrations in plasma of 67 passive smokers at baseline and after 2 mo of daily intervention with AOs or placebo. The study subjects (47 females, 20 males; mean age 46 +/-15) were randomized into one of three treatment groups: vitamin C, "mixture" (vitamin C, vitamin E, and a-lipoic-acid), and placebo. Investigated confounders included plasma baseline AO levels, lipid and total cholesterol profiles, transferrin saturation, and C-reactive protein. Plasma F2IsoP concentrations of subjects in the vitamin C and mixture groups decreased significantly by 17.2 pmol/l (P = 0.0105) and 19.2 pmol/l (P = 0.0083) when compared with the placebo group (11.4% and 12.7%, respectively). Daily AO supplementation (especially with vitamin C) decreases this oxidative stress biomarker in passive smokers. This finding might be of importance for the prevention of ETS-associated adverse health effects in nonsmokers.

Adult↗

PubMed2002

Ozone exposure activates oxidative stress responses in murine skin.

Ozone (O(3)) is among the most reactive environmental oxidant to which skin is exposed. O(3) exposure has previously been shown to induce antioxidant depletion as well as lipid and protein oxidation in the outermost skin layer, the stratum corneum (SC), but little is known regarding the potential effects of O(3) on the skin epidermis and dermis. To evaluate such skin responses to O(3), SKH-1 hairless mice were exposed for 2 h to 8.0 ppm O(3) or to ambient air. O(3) exposure caused a significant increase in skin carbonyls (28%) compared to the skin of air exposed control animals. An evident increase in 4-hydroxynonenal-protein adducts was detected after O(3) exposure. O(3) exposure caused a rapid up-regulation of HSP27 (20-fold), and more delayed induction of HSP70 (2.8-fold) and heme oxygenase-1 (5-fold). O(3) exposure also led to the induction of nitric oxide synthase (iNOS) 6-12 h following O(3) exposure. We conclude that skin exposure to high levels of O(3) not only affects antioxidant levels and oxidation markers in the SC, but also induces stress responses in the active layers of the skin, most likely by indirect mechanisms, since it is unlikely that O(3) itself penetrates the protective SC layers.

Aldehydes↗

PubMed2002

ESR and cell culture studies on free radical-scavenging and antioxidant activities of isoflavonoids.

Isoflavonoids are thought to be the biologically active components in soy that play a role in the prevention of coronary heart disease and breast and prostate cancer. Mechanisms to explain how isoflavonoids mediate beneficial effects have not yet been clearly established. This study was undertaken to investigate the free radical-scavenging and antioxidant activities of various structure-related isoflavonoids including genistein, daidzein, biochanin A, and genistin in a cell-free and an endothelial cell model system. Electron spin resonance spectroscopy and spin trapping techniques were applied to evaluate the ability of isoflavonoids to scavenge hydroxyl, superoxide, nitric oxide, diphenylpicrylhydrazyl, galvinoxyl, and lipid-derived radicals. All isoflavonoids tested had no significant scavenging effects on the aforementioned radicals in concentrations up to 1.0 mM. However, at a physiologically achievable concentration of 5 nM, both genistein and daidzein slightly increased intracellular-reduced glutathione levels approximately by 10 and 30%, respectively, in human endothelial cells, whereas cellular alpha-tocopherol and uric acid remained unchanged by the isoflavonoid treatments. Present data indicate that free radical-scavenging activities of the isoflavonoids tested probably do not substantially contribute to their antioxidant properties. The ability of genistein and daidzein to increase cellular GSH (reduced glutathione) might be important for their action in biological system.

Anticarcinogenic Agents↗

PubMed2002

Factors associated with oxidative stress in human populations.

Oxidation of biomolecules may play a role in susceptibility to a number of diseases. However, there are few large-scale survey data describing oxidative damage that occurs in humans and the demographic, physical, or nutritional factors that may be associated with it. Such information is essential for the design and analysis of studies investigating the role of oxidative stress in health and disease. This paper presents data on levels of two biomarkers of lipid peroxidation, malondialdehyde and F(2)-isoprostanes, in 298 healthy adults aged 19-78 years. The study was conducted in Berkeley and Oakland, California, in 1998-1999. Sex was the strongest predictor of lipid peroxidation as measured by both biomarkers (p < 0.0001); it was stronger than smoking. C-reactive protein was positively associated with lipid peroxidation (p = 0.004), as was plasma cholesterol. Plasma ascorbic acid had a strong inverse relation (p < 0.001) with both biomarkers. Plasma beta-carotene was also associated with F(2)-isoprostanes. Other plasma antioxidants were not associated with lipid peroxidation biomarkers, once ascorbic acid was included in the multivariate model. Future surveys and epidemiologic studies should measure at least one marker of oxidative damage, as well as plasma ascorbic acid. These data would permit a better understanding of the role that oxidants and antioxidants play in the health of human populations.

Adult↗

PubMed2002

Antioxidant and prooxidant activities of alpha-lipoic acid and dihydrolipoic acid.

Reactive oxygen (ROS) and nitrogen oxide (RNOS) species are produced as by-products of oxidative metabolism. A major function for ROS and RNOS is immunological host defense. Recent evidence indicate that ROS and RNOS may also function as signaling molecules. However, high levels of ROS and RNOS have been considered to potentially damage cellular macromolecules and have been implicated in the pathogenesis and progression of various chronic diseases. alpha-Lipoic acid and dihydrolipoic acid exhibit direct free radical scavenging properties and as a redox couple, with a low redox potential of -0.32 V, is a strong reductant. Several studies provided evidence that alpha-lipoic acid supplementation decreases oxidative stress and restores reduced levels of other antioxidants in vivo. However, there is also evidence indicating that alpha-lipoic acid and dihydrolipoic acid may exert prooxidant properties in vitro. alpha-Lipoic acid and dihydrolipoic acid were shown to promote the mitochondrial permeability transition in permeabilized hepatocytes and isolated rat liver mitochondria. Dihydrolipoic acid also stimulated superoxide anion production in rat liver mitochondria and submitochondrial particles. alpha-Lipoic acid was recently shown to stimulate glucose uptake into 3T3-L1 adipocytes by increasing intracellular oxidant levels and/or facilitating insulin receptor autophosphorylation presumably by oxidation of critical thiol groups present in the insulin receptor beta-subunit. Whether alpha-lipoic acid and/or dihydrolipoic acid-induced oxidative protein modifications contribute to their versatile effects observed in vivo warrants further investigation.

Animals↗

PubMed2002

Flavonoids differentially regulate IFN gamma-induced ICAM-1 expression in human keratinocytes: molecular mechanisms of action.

The effect of plant flavonoids on intercellular adhesion molecule-1 (ICAM-1) expression in human keratinocyte was investigated. ICAM-1 is known to mediate skin inflammation. Among the flavonoids tested, taxifolin was the most potent in inhibiting interferon gamma (IFN gamma)-induced ICAM-1 protein as well as mRNA expression in human keratinocytes. Much smaller dosages of taxifolin were required in primary keratinocytes compared to HaCaT (immortalized cell) to achieve similar levels of inhibition in the inducible ICAM-1 expression. Regulation of inducible ICAM-1 expression by taxifolin was at transcriptional level by inhibiting the activation of signal transducers and activators of transcription (STAT)1 and protein tyrosine phosphorylation of Janus kinase (JAK)1 suggesting that the JAK-STAT pathway may be the molecular site of action of taxifolin. Finally, taxifolin pre-treatment also potently inhibited IFN gamma-induced ICAM-1 expression in a reconstructed human skin equivalent suggesting therapeutic potential of taxifolin in skin pathological conditions related to increased cell adhesion and inflammation.

Apigenin↗

PubMed2002

Free radical scavenging activity of red ginseng aqueous extracts.

This study was performed to investigate the free radical scavenging activity of Panax red ginseng C.A. Meyer aqueous extract on 1,1-dipheny-2-picrylhydrazyl (DPPH), carbon-centered radical, hydroxyl and superoxide radicals using Electron Spin Resonance (ESR) spectrometer and spin-trapping techniques. Two different Red ginseng aqueous extracts prepared by boiling water or room temperature extraction exhibited no significant difference in free radical scavenging activity. Ginseng extracts completely eliminated DPPH radical at 2 mg/ml. About 0.5 mg/ml ginseng extracts quenched 80% carbon-centered free radicals generated from 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). Hydroxyl radical and superoxide radical were generated by UV irradiation and trapped by 5,5-dimethyl-l-pyrroline-N oxide (DMPO). Ginseng extracts scavenged 40% of hydroxyl radical at 0.1 mg/ml. Two mg/ml ginseng extracts completely scavenged superoxide radical. Ginseng extracts did not scavenge nitric oxide. The ESR data demonstrate that red ginseng aqueous extract is not a strong free radical scavenger.

Bepridil↗

PubMed2002

R-alpha-lipoic acid action on cell redox status, the insulin receptor, and glucose uptake in 3T3-L1 adipocytes.

The insulin signaling pathway has been reported to mediate R-alpha-lipoic acid- (R-LA-)-stimulated glucose uptake into 3T3-L1 adipocytes and L6 myotubes. We investigated the role of the thiol antioxidant dihydrolipoic acid (DHLA) and intracellular glutathione (GSH) in R-LA-stimulated glucose transport and explored the hypothesis that R-LA could increase glucose uptake into 3T3-L1 adipocytes in an oxidant-mimetic manner. R-LA pretreatment of 3T3-L1 cells stimulated glucose transport at early time points (30 min - 6 h), whereas it inhibited glucose uptake at later time points. Analysis of the oxidized and reduced content of LA in cells and medium showed that >90% of lipoic acid present was in its oxidized form. Furthermore, all oxidized forms of LA (S-, R-, and racemic LA) stimulated glucose uptake, whereas the reduced form, dihydrolipoic acid, was ineffective. Intracellular GSH levels were not changed at the early time points (before 12 h), while longer preincubation (24 - 48 h) of cells with R-LA significantly increased intracellular GSH. Pretreatment of adipocytes with R-LA increased intracellular peroxide levels at early time points (30 min - 6 h), after which it was decreased (12 - 48 h). R-LA also increased tyrosine phosphorylation of immunoprecipitated insulin receptors from 3T3-L1 adipocytes. These results indicate that (i) 3T3-L1 adipocytes have a low capacity to reduce R-LA and the oxidized form of lipoic acid is responsible for stimulating glucose uptake, (ii) R-LA modulates glucose uptake by changing the intracellular redox status, and (iii) the insulin receptor is a potential cellular target for R-LA action.

3T3 Cells↗

PubMed2002

Antioxidant activities of pomegranate fruit extract and its anthocyanidins: delphinidin, cyanidin, and pelargonidin.

Antioxidant activities of freeze-dried preparations of a 70% acetone extract of pomegranate (Punica granatum L.) and its three major anthocyanidins (delphinidin, cyanidin, and pelargonidin) were evaluated. Free radical scavenging activities were examined using an ESR technique with spin trapping; DMPO for hydroxyl (.OH) and superoxide (O(2)(.-) ) radicals; and [(MGD)(2)Fe(2+)] for nitric oxide (NO). Inhibitory effects on lipid peroxidation were estimated by the levels of malonaldehyde and 4-hydroxyalkenals in rat brain homogenates. Pomegranate extract exhibited scavenging activity against.OH and O(2)(.-). Anthocyanidins inhibited a Fenton reagent.OH generating system possibly by chelating with ferrous ion. Anthocyanidins scavenged O(2)(.)- in a dose-dependent manner. The ID(50) values of delphinidin, cyanidin, and pelargonidin were 2.4, 22, and 456 microM, respectively. In contrast, anthocyanidins did not effectively scavenge NO. Anthocyanidins inhibited H(2)O(2)-induced lipid peroxidation in the rat brain homogenates. The ID(50) values of delphinidin, cyanidin, and pelargonidin for them were 0.7, 3.5, and 85 microM, respectively. These findings suggest that the above anthocyanidins contribute to the antioxidant activity of pomegranate fruits.

Anthocyanins↗

PubMed2002

Impact of water-dispersible beadlets as a vehicle for the delivery of carotenoids to cultured cells.

Water-dispersible beadlets of carotenoids were used as supplements for human umbilical vein endothelial cells (HUVECs), human peripheral blood mononuclear cells (PBMCs) and human monocytes. Stability, cellular association and cytotoxicity of the carotenoid beadlets were compared with carotenoids delivered with tetrahydrofuran (THF). Incubations with lycopene, beta-carotene, lutein and astaxanthin dissolved in THF resulted in a lower stability in the medium, lower cellular association, and a higher standard deviation. Beadlets provided 60, 4, 6, and 2 times greater accumulation of lycopene, beta-carotene, lutein and astaxanthin, respectively, by PBMCs than THF. The cellular association of carotenoids delivered by THF seems to be more carotenoid-specific than when carotenoids are delivered by beadlets. After 48 h of incubation under cell culture conditions all of the four carotenoids (1 microM) delivered by beadlets to the medium showed a reduction less than 30%. In addition, no cytotoxic effect of the carotenoid beadlets or the vehicle alone was detected in a concentration range of 0.5-5 microM. The results show that beadlets are a non-toxic vehicle for supplementing and stabilizing carotenoids in culture media offering a reasonable compromise in term of cell accumulation efficiency.

Carotenoids↗

PubMed2002

S-Adenosylmethionine: molecular, biological, and clinical aspects--an introduction.

In clinical research, a novel approach has emerged: some of the essential nutrients are being used to treat pathologic conditions. Many of these nutrients, including methionine, must first be activated in the liver or in other tissues before they can exert their key functions. However, this activating process is impaired in disease states and, as a consequence, nutritional requirements change. For instance, for methionine to act as the main cellular methyl donor, it must first be activated to S-adenosylmethionine (SAMe; also known as ademethionine). SAMe is required and is of fundamental importance for the metabolism of nucleic acids and polyamines, the structure and function of membranes, and as a precursor of glutathione. These processes are often seriously altered in various pathologic states addressed in this symposium, but they cannot be restored by simply administering methionine. For instance, in liver disease associated with impairment of the enzyme that activates methionine to SAMe, supplementation with methionine is useless and may even become toxic as it accumulates because it is not used. Accordingly, one must correct the lack of SAMe by bypassing the deficiency in enzyme activation; this is done by providing the product of the defective reaction, namely SAMe. Under these pathologic conditions, SAMe becomes crucial for the functioning of the cell. Thus SAMe, which is found in all living organisms, becomes the essential nutrient instead of methionine. This symposium reviewed the biological and corresponding molecular aspects of SAMe metabolism and the clinical consequences of its deficiency or supplementation in various tissues.

Humans↗

PubMed2002

Bioflavonoid-rich botanical extracts show antioxidant and gene regulatory activity.

Reactive oxygen and nitrogen metabolites are obligatory and essential products of metabolism. Unregulated increase in their production is associated with a number of chronic illnesses. Diets rich in fruits, vegetables, and wines are implicated in the prevention of chronic diseases. Molecular mechanisms by which fruits and vegetables confer their disease-preventive actions are poorly defined. However, recent developments in the fields of genomics and bioinformatics provide powerful tools to investigate the mechanisms by which botanicals affect cellular functions. This monograph illustrates the potential of large-scale messenger RNA analysis to unravel the role of transcription in mediating the effects of botanical extracts with antioxidant properties. The application of microarrays and oligonucleotide arrays shows multiple effects of antioxidant extracts on the expression of a broad spectrum of genes.

Animals↗

PubMed2002

Antioxidant supplementation decreases lipid peroxidation biomarker F(2)-isoprostanes in plasma of smokers.

Free radicals in cigarette smoke (CS) cause oxidative damage to proteins, DNA, and lipids, contributing to the pathobiology of atherosclerosis, heart disease, and cancer. In vitro studies have shown that antioxidants quench free radicals and ameliorate certain aspects of biomolecular damage caused by CS. It is hypothesized that a combination of antioxidants is more effective than a single antioxidant, due to their interactions. To investigate whether supplemental antioxidants reduce CS-related lipid peroxidation in vivo and whether they are more effective in combination, we conducted an intervention study in smokers. In a randomized double-blind placebo-controlled trial, we investigated whether vitamin C or an antioxidant mixture containing vitamin C, alpha-lipoic acid, and vitamin E decreases plasma F(2)-isoprostane levels, an index of oxidant stress, in smokers. Plasma of 126 smokers (mean age, 46 years; age range, 20-78 years) was analyzed for F(2)-isoprostanes at baseline and after intervention with antioxidants and placebo. In smokers with a body mass index (BMI) above the median, 2 months of daily supplementation with 500 mg of vitamin C decreased plasma F(2)-isoprostane levels by 28.8 pmol/liter when compared with the placebo group (P = 0.001); levels in the mixture group were 7.45 pmol/liter lower after treatment, but this difference was not statistically significant (P = 0.14). There was no treatment effect in smokers with a low BMI. BMI was significantly positively associated with plasma F(2)-isoprostane levels (trend P = 0.001). Antioxidants decrease smoking-related lipid peroxidation markers of oxidative stress in humans with high BMI. Our results do not indicate that an antioxidant combination is more effective than vitamin C alone. The intake of antioxidants may help prevent smoking-related diseases. Smoking cessation should still be considered the most effective way to prevent smoking-related diseases.

Adult↗