Plasma oxidative stress is induced by single‐sprint anaerobic exercise in young cigarette smokers

Cigarette smoking increases oxidative stress, which is a risk factor for several diseases. Smoking has also been reported to enhance plasma oxidative stress during strenuous exercise. However, no prior study has examined the changes in plasma oxidative stress after single‐sprint anaerobic exercise in cigarette smokers. The purpose of this study was to investigate these changes in young cigarette smokers by measuring reactive oxygen species generation and total antioxidant content. Participants were 15 male smokers (mean age: 25·9 ± 2·9 years) and 18 male non‐smokers (mean age: 24·2 ± 4·3 years). Hydroperoxide concentration and biological antioxidant potential (BAP) in plasma were measured at baseline and after the Wingate anaerobic test. A significant interaction between group and time was observed for plasma hydroperoxide concentration (P = 0·037). Plasma hydroperoxide concentration was significantly increased after exercise in both smokers and non‐smokers (P = 0·001 and <0·001, respectively). However, no significant interaction was observed between groups by time on plasma BAP (P = 0·574), and a main effect of time was observed (P<0·001). Plasma BAP was significantly increased after exercise in both groups (both, P<0·001). These findings indicate that plasma oxidative stress is higher in cigarette smokers than in non‐smokers after single‐sprint anaerobic exercise, which may increase the risk of oxidative damage.     

Facilitated nitration and oxidation of LDL in cigarette smokers

BACKGROUND: Cigarette smoking increases the risk of developing atherosclerosis and ischaemic heart disease. Smoking-induced oxidative stress is considered to favour oxidation of low-density lipoprotein (LDL) and subsequently promotes the atherogenic process. We investigated whether peroxynitrite, a reaction product of cigarette smoke, is involved in facilitated oxidation of LDL in smokers. MATERIALS AND METHODS: Plasma LDL was obtained from 10 healthy asymptomatic cigarette smokers and 10 healthy nonsmokers. The state of enhanced oxidative stress in the plasma was assessed by LDL subfraction assay using anion-exchange high-performance liquid chromatography (AE-HPLC) and measurements of thiobarbituric acid-reactive substances (TBARS), 8-hydroxydeoxyguanosine (8-OHdG), vitamin E, 3-nitrotyrosine and 3-chlorotyrosine. RESULTS: Smokers showed a significantly higher level of TBARS and 8-OHdG as well as a significantly lower level of vitamin E than nonsmokers, even after stopping smoking for 10 h or more. The LDL subfraction assay demonstrated an increase in oxidatively modified LDL, as expressed by lower levels of LDL1 and higher levels of LDL2. The 3-nitrotyrosine levels in apolipoprotein B in LDL were significantly higher in smokers than nonsmokers, while the 3-chlorotyrosine levels remained unchanged. In addition, these changes observed in the smokers were further accelerated within 30 min after resumption of cigarette smoking when compared with the levels before smoking resumption. CONCLUSION: The present study suggests that peroxynitrite plays a significant role in oxidative modification of plasma LDL induced by cigarette smoking.     

Aging and drug interactions. II. Effect of phenytoin and smoking on the oxidation of theophylline and cortisol in healthy men

The effect of age on the induction of theophylline metabolism by phenytoin was examined in healthy young and old male cigarette smokers (greater than or equal to 20 cigarettes/day) and nonsmokers. Two single dose studies of theophylline pharmacokinetics were performed, one as a base-line control and another after a 2-week course of phenytoin. Phenytoin was administered as an i.v. loading dose followed by oral ingestion. The dose was adjusted to achieve total phenytoin plasma concentrations within a low therapeutic range (10-13 micrograms/ml). Free phenytoin concentrations in plasma were slightly higher in old (nonsmokers 0.84 +/- 0.13 micrograms/ml; smokers 0.89 +/- 0.12 micrograms/ml) than in young (nonsmokers 0.75 +/- 0.10 micrograms/ml; smokers 0.72 +/- 0.10 micrograms/ml) subjects, but the differences were not significant. Base-line plasma theophylline clearance was 30% lower in old compared with young nonsmokers (34.0 +/- 2.5 vs. 48.8 +/- 2.6 ml/hr/kg, P less than .001), whereas the small age difference between old and young smokers (86.0 +/- 8.4 vs. 72.4 +/- 8.0 ml/hr/kg) was not significant. Smokers had higher values of theophylline clearance than nonsmokers regardless of age. Half-life was prolonged in old nonsmokers in proportion to decreased clearance, despite a slight decrease in volume of distribution. Phenytoin induced theophylline metabolism to an equal degree in both age groups and in both smokers (young 42.6 +/- 6.5%; old 47.3 +/- 3.6%) and nonsmokers (young 56.3 +/- 8.8%; old 45.4 +/- 6.4%). The magnitude of its induction in smokers was additive to that of cigarette smoking. Old age was associated with a modest selective reduction in N-demethylated metabolic pathways to 3-methylxanthine and 1-methyluric acid, whereas smoking preferentially induced the formation of these products. Phenytoin increased the production of all theophylline primary metabolites to an equal degree in both old and young subjects. The urinary excretion of 6 beta-hydroxycortisol was not influenced significantly by age or smoking and increased 2- to 3-fold in all subject groups with phenytoin. These results confirm earlier observations of a reduction in basal oxidative capacity in elderly nonsmoking males. They also demonstrate that the ability to induce the metabolism of theophylline by smoking or phenytoin and the ability to induce the metabolism of cortisol by phenytoin are maintained in old age.     

Increased serum iron may contribute to enhanced oxidation of low-density lipoprotein in smokers in part through changes in lipoxygenase and catalase

BACKGROUND: Increased oxidative stress is considered to be causative for cardiovascular disease (CVD) in smokers, but its mechanisms are still unclear. We compared oxidative stress markers between male smokers and male nonsmokers. METHODS: Twenty-three healthy men (11 nonsmokers and 12 smokers) were enrolled, and blood samples after 12 h of fasting were collected to assess plasma lipids and oxidative stress markers. The effects of iron loading on 12-lipoxygenase (12-LO) expression and activity in human umbilical vein endothelial cells (HUVECs) were tested in vitro to investigate the relevance of iron to oxidation potential in vivo. RESULTS: Higher levels of plasma-oxidized low-density lipoprotein (LDL) and lipid peroxide (LPO), and higher oxidizability of LDL were observed in smokers than in nonsmokers. Higher levels of serum iron and lower levels of plasma vitamin E were observed in smokers than in nonsmokers. Stepwise multiple regression analysis showed that serum iron was an independent determinant for both plasma-oxidized LDL and lag time of LDL oxidation. Iron loading enhanced 12-LO expression threefold and its activity 1.5-fold. Moreover, iron loading decreased catalase expression by 50% and significantly reduced its activity by 75%. CONCLUSIONS: Enhanced oxidative stress in smokers may be due to increased iron levels. Iron-induced modulation of expression and activity of 12-LO and catalase may be relevant to increased iron-related oxidative stress as observed in smokers.     

Stimulatory effect of cigarette smoking on the 15 alpha-hydroxylation of estradiol by human term placenta

OBJECTIVE: Our objective was to characterize the oxidative metabolism of estradiol by human term placenta and its modulation by cigarette smoking. METHODS: Placental microsomes were prepared from term placentas obtained from 13 cigarette smokers (20 to 30 cigarettes per day until the time of delivery) and 13 control subjects who were nonsmokers. Estrogen metabolism was studied by incubation of 250 nmol/L [(3)H]estradiol with placental microsomes and NADPH, and the estrogen metabolites were determined by HPLC and gas chromatography-mass spectrometry. RESULTS: 2-Hydroxyestradiol was the major hydroxyestrogen detected, followed by 6alpha-hydroxyestradiol. Small amounts of several other hydroxyestrogen metabolites (4-hydroxyestradiol, 6beta-hydroxyestradiol, 7alpha-hydroxyestradiol, and 16alpha-hydroxyestradiol) were also detected. Large amounts of estrone plus small amounts of 2-hydroxyestrone and unidentified nonpolar metabolites were formed. Cigarette smoking stimulated the placental hydroxylation of benzo[a ]pyrene by about 16-fold. Cigarette smoking had little or no effect on the overall rate of placental estradiol metabolism or on the formation of estrone, 2-hydroxyestradiol, 2-hydroxyestrone, or 16alpha-hydroxyestradiol. However, placental formation of 4-hydroxyestradiol and 7alpha-hydroxyestradiol was increased 38% (P =.08) and 150% (P =.05), respectively, in cigarette smokers. The formation of 6alpha-hydroxyestradiol was decreased 33% (P =.04). Metabolic formation of 15alpha-hydroxyestradiol was observed during incubations of estradiol with placental microsomes from 11 of the 13 cigarette smokers, but this metabolite was not detected during incubations with placental microsomes from any of the 13 nonsmokers. Analysis of data from all 26 placentas showed that the 15alpha-hydroxylation of estradiol was highly correlated with benzo[a ]pyrene hydroxylation (r = 0.93; P <.001). CONCLUSIONS: Many hydroxylated estradiol metabolites were formed by placental microsomes from cigarette smokers and nonsmokers. 15alpha-Hydroxylation of estradiol was markedly stimulated in the placentas of cigarette smokers.     

Cigarette smoking and theophylline metabolism: effects of phenytoin

The induction of theophylline clearance by phenytoin was investigated in 12 young male subjects (six nonsmokers and six cigarette smokers). Each subject received intravenous theophylline to determine baseline pharmacokinetics. This was followed by an intravenous loading dose of phenytoin sodium and oral maintenance dosing for 2 weeks, after which the intravenous theophylline study was repeated. Phenytoin concentrations were similar in nonsmokers (10.8 +/- 2.0 micrograms/ml) and smokers (11.5 +/- 0.9 micrograms/ml). Control theophylline elimination half-life was 35% less and clearance 88% greater in smokers than in nonsmokers. The proportionate changes in half-life (26.8% +/- 5.6% in smokers and 25.8% +/- 3.5% in nonsmokers) and clearance (48.0% +/- 10.1% in smokers and 39.7% +/- 7.2% in nonsmokers) as the result of phenytoin induction were similar in both groups. These results demonstrate that the induction of theophylline clearance by phenytoin is additive to that caused by cigarette smoking and provide support for the suggestion that theophylline metabolism is influenced by multiple polymorphisms.     

Effects of cigarette smoking on the antioxidant defence in young healthy male volunteers

Cigarette smoking induces a significant oxidant effect related to variety of free radical-related diseases often affecting the upper respiratory tract, unless it is effectively compensated by the antioxidant barriers of the humans. In the present study, the evaluation of the antioxidant compensatory mechanisms, by estimating the antioxidant capacity of extracellular defence (saliva and plasma) and the intracellular resistance of peripheral lymphocytes to oxidative stress in young healthy smokers, was investigated. Twenty young healthy male smokers and 20 age-matched non-smokers with similar dietary profiles were enrolled in the study. Total saliva and plasma samples were collected from both groups, and total antioxidant capacity (TAC) and lag time were estimated. The latter was also repeated in smokers just after a cigarette smoking. Peripheral lymphocytes isolated from the subjects of both groups were also tested for their inherent DNA damage as well as for their ability to resist H2O2-induced DNA damage by using the comet assay. TAC of plasma was found significantly higher in smokers compared to non-smokers (p <0.004), whereas no difference was recorded in plasma lag time values. Lymphocytes of smokers manifested a significantly decreased oxidant resistance (increased DNA fragmentation) to H2O2, in comparison to non-smokers. Our results indicate that young smokers do not manifest different salivary antioxidant defence than non-smokers. They exhibit, however, a higher plasma antioxidant capacity, but a significantly reduced ability of blood lymphocytes, to resist to H2O2-induced DNA damage.     

Effect of cigarette smoking on the oxidant/antioxidant balance in healthy subjects

BACKGROUND AND PURPOSE: Cigarette smoking has been associated with the development of cardiovascular disease and cancer. Even though the molecular mechanism(s) are not clear, the pathology has been related to oxygen free radicals present in cigarette smoke. Thus, the main objective of this study was to establish the changes in the oxidation/antioxidation balance induced by cigarette smoking. METHODS: Thirty healthy subjects (15 smokers and 15 nonsmokers) of both sexes were studied. The smokers group had smoked a mean of 14 cigarettes per day for an average of 4.5 years. Fasting serum levels of malondialdehyde (MDA), a marker of oxidative stress, nitric oxide (NO), reduced glutathione (GSH), and vitamin C (ascorbic and dehydroascorbic acids) were measured. RESULTS: Fasting NO concentration was significantly higher in smokers (51.3 +/- 5.3 microM) than in nonsmokers (35.2 +/- 4.8 microM, P < 0.05). The smokers had significantly higher serum dehydroascorbic acid levels (2.4 +/- 0.5 mg/dL, P < 0.03) than the nonsmokers (1.08 +/- 0.08 mg/dL). No significant differences were observed in the levels of ascorbic acid, MDA, and GSH between the smokers and nonsmokers. CONCLUSIONS: Our results suggest that exposure to cigarette smoke increases NO synthesis, such that NO may act in a compensatory way as an inhibitor of lipid peroxidation. Smoking also activates other antioxidative mechanisms such as involving vitamin C. These protective mechanisms appear to be enough in preventing accumulation of oxidative products such as MDA and avoiding oxidative damage.     

Oxidative stress in pathogenesis of COPD

Cigarette smoke and aging are major risk factors of chronic obstructive pulmonary disease(COPD). It remains unsolved how long -term smoking with age affects the molecular responses in the lung. Respiratory tract is the major interface to the environment and is rich in glutathione, which protects lung from oxidative stress. We performed bronchoalveolar lavage for nonsmokers and smokers of various ages, who were further categorized according to the presence of emphysema on high-resolution computed tomography. We thus evaluated glutathione antioxidant system in BAL fluid. Characterization of older smokers with long-term smoking histories, contrasted with young recent smokers, may in part explain the predisposition of the lungs to destructive lung diseases. On the other hands, oxidative stress results from an imbalance in aerobic metabolism and poses a serious threat to cellular apoptosis, leading to emphysematous lung destruction. The therapeutic interference with targeted up-regulation of protective mechanisms might be critical for the success of future COPD therapies.     

Cigarette smoking and theophylline metabolism: effects of cimetidine

The inhibition of theophylline metabolism by cimetidine was investigated in young male cigarette smokers (greater than 20 cigarettes/day) and nonsmokers by stable isotope methodology. Subjects received oral theophylline (510 mg/day) for 14 days and cimetidine (1200 mg/day) over days 1 to 7 or 8 to 14. On days 7 and 14, a tracer dose (10 mg) of stable isotope-labeled theophylline was injected intravenously with the oral dose of theophylline. Serial plasma samples were then obtained for 24 hours and both molecular forms of theophylline were assayed by mass spectrometry after purification by HPLC. Theophylline bioavailability, volume of distribution, and protein binding were of the same order in both groups and were not affected by cimetidine. Although the basal theophylline elimination rate constant was 46% greater and clearance was 54% greater in smokers than in nonsmokers, the proportionate changes in steady-state plasma concentrations, t1/2, and clearance due to cimetidine were much the same in both groups. Plasma thiocyanate concentrations were higher in smokers than in nonsmokers and were related to theophylline clearance. Our findings indicate that cimetidine inhibits theophylline metabolism to a similar extent in both smokers and nonsmokers. Determination of plasma thiocyanate levels may be valuable in the prediction of theophylline clearance.     

Antioxidant effect of Phyllanthus amarus after moderate-intensity exercise in sedentary males: a randomized crossover (double-blind) study

[Purpose] We aimed to evaluate the effects of Phyllanthus amarus (PA) on oxidative stress and damage, inflammation, and soreness in muscle after a single session of moderate-intensity exercise. [Subjects and Methods] Twelve men randomly participated in 2, three-day phases with a one-week washout period. On the first day, participants consumed two capsules of PA or placebo control (CTL) before 20 min of cycling. They then consumed four capsules on the same day after exercise and six capsules/day for the next two days. Blood samples were obtained before, immediately after exercise and 24 h and 48 h after exercise. The pain tolerance was measured at both legs. [Results] Plasma vitamin C levels in the PA group were higher than those in the CTL group after exercise. At 48 h after exercise, vitamin C levels were higher in the PA group, but those in the CTL group were lower than the pre-exercise levels. However, plasma levels of creatine kinase were increased in both groups after exercise compared with the pre-exercise levels. The neutrophil count was higher immediately after exercise than the pre-exercise levels in the CTL group. [Conclusion] Acute supplementation with PA improves antioxidant status after a single session of moderate-intensity exercise.     

Transdermal nicotine mimics the smoking-induced endothelial dysfunction

BACKGROUND: Cigarette smoking is a major risk factor for coronary artery disease and causes endothelial dysfunction, perhaps by decreasing the availability of nitric oxide availability in arteries and veins. Nicotine in cigarette smoke may be responsible for this impaired endothelial response. METHODS: We studied nine healthy nonsmokers and 12 healthy mild to moderate smokers by use of the dorsal hand vein compliance technique. Dose-response curves to bradykinin and sodium nitroprusside were obtained to test the endothelium-dependent and endothelium-independent vasorelaxation before and during the use of a nicotine (21 mg) patch. Mean arterial blood pressure and heart rate were measured beat-to-beat during the 4-hour study and serial blood samples were drawn to assay plasma thromboxane B2 levels. RESULTS: Transdermal nicotine reduced the venous responsiveness to bradykinin in nonsmokers (Emax = 88.0% +/- 17.9% and 54.3% +/- 14.9%, respectively, before and after the nicotine patch; P < .05); the latter response was similar to that in smokers (Emax = 56.3% +/- 16.6%). Sodium nitroprusside-induced venodilation was unaltered. Mean arterial blood pressure increased in both smokers and nonsmokers. Transdermal nicotine increased the plasma thromboxane B2 concentrations only among nonsmokers. CONCLUSION: These findings indicate that nicotine can have a major role in the impaired endothelial function in smokers. The results probably also reflect what occurs in arterial beds because the nicotine patches increased the mean arterial blood pressure in both smokers and nonsmokers.     

Enhanced exercise-induced plasma cytokine response and oxidative stress in COPD patients depend on blood oxygenation

In healthy subjects, hypoxemia and exercise represent independent stressors promoting the exercise-induced cytokine response and oxidative stress. We hypothesized that hypoxemia in patients with chronic obstructive pulmonary disease (COPD) may affect the cytokine production and/or the changes in oxidant-antioxidant status in response to maximal exercise. Exercise-induced changes in PaO2 allowed to transiently increase or decrease baseline hypoxemia and to point out its specific action on muscle metabolism. COPD patients with severe to moderate hypoxemia (56 < PaO2 < 72 mmHg) performed an incremental cycling exercise until volitional exhaustion. Two cytokines [interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha] and three blood indices of oxidative stress [plasma thiobarbituric acid reactive substances (TBARS) and two antioxidants, reduced erythrocyte glutathione (GSH), and reduced plasma ascorbic acid, RAA] were measured at rest, then during and after exercise. The changes in the cytokine levels and oxidant-antioxidant status were analysed in relation with the baseline PaO2 and its exercise-induced variations. Data were compared with those obtained in an age- and body mass index-matched group of healthy subjects. Compared with healthy subjects, COPD patients presented a marked accentuation of exercise-induced increase in IL-6 level and earlier changes in their oxidant-antioxidant status. Resting levels of IL-6 and TNF-alpha and exercise-induced peak variations of TBARS, IL-6 and TNF-alpha were negatively correlated with the baseline PaO2. In COPD patients, the peak increases in IL-6 and TBARS were attenuated when exercise hyperventilation reduced the baseline hypoxemia. Our study indicates that the PaO2 level affects both the exercise-induced oxidative stress and cytokine response in hypoxemic COPD patients.     

Urinary hydrogen peroxide: a probable marker of oxidative stress in malignancy

BACKGROUND: Urinary hydrogen peroxide was postulated to be a biomarker of oxidative stress. We estimated urinary hydrogen peroxide along with other established parameters of oxidative stress in malignancies where oxidative stress is well documented. METHODS: The oxidative stress markers tested were concentrations of erythrocyte glutathione, erythrocyte malonaldehyde (MDA) and plasma hydroperoxide, and activities of plasma glutathione-S-transferase (GST) and erythrocyte catalase. Urinary hydrogen peroxide was measured by a modified ferrous ion oxidation xylenol orange version-2 (FOX-2) method on a spot random sample of urine. RESULTS: In healthy controls (n=10), erythrocyte glutathione concentration was 4.41+/-0.057mg/g of hemoglobin, plasma hydroperoxide was 2.5+/-0.07 micromol/l, erythrocyte MDA was 0.9+/-0.15 nmol/ml of packed cell suspension and erythrocyte catalase and plasma GST were 74.66+/-9.2/s/ml of packed cell suspension and 6.12+/-0.84 IU/l, respectively. In cancer patients (n=25), erythrocyte glutathione, plasma hydroperoxide and erythrocyte MDA were 9.32+/-0.42 mg/g of hemoglobin, 6.2+/-0.13 micromol/l and 2.3+/-0.27 nmol/ml of packed cell suspension, respectively; and activities of erythrocyte catalase and plasma GST were 151.04+/-6.5/s/ml of packed cell suspension and 10.9+/-0.36 IU/l, respectively. Urinary hydrogen peroxide concentration was 15+/-9.8 micromol/l in the healthy controls and 56.3+/-3.9 micromol/l in cancer patients. CONCLUSION: Urinary hydrogen peroxide may be a marker of oxidative stress in malignancies.     

Aging and drug interactions. I. Effect of cimetidine and smoking on the oxidation of theophylline and cortisol in healthy men

The effect of age on the inhibition of theophylline metabolism was investigated in young and old male cigarette smokers (greater than 20 cigarettes/day) and nonsmokers by stable isotope methodology. Subjects received oral theophylline (510 mg/day) for 14 days and cimetidine (1200 mg/day) during days 1 to 7 or 8 to 14. On days 7 and 14, a tracer dose (10 mg i.v.) of stable isotope-labeled theophylline was administered with the oral dose of theophylline. Plasma clearance in old nonsmokers was 33% less than in young nonsmokers. Values in both young and old smokers were not significantly different but exceeded those in non-smokers. Because volume of distribution was similar in all groups, the half-lives were prolonged in proportion to the decrease in clearance. Although smoking was associated with selective induction of the formation of 3-methylxanthine and 1-methyluric acid, the effect of cimetidine was nonselective and the proportionate inhibitory effects of cimetidine on theophylline metabolism did not differ with age or smoking status. The excretion of 6 beta-hydroxycortisol was similar in smokers and non-smokers but was slightly inhibited by cimetidine. Cimetidine also reduced the interindividual variation in the absorption of theophylline. Despite a reduction in the basal oxidative capacity in healthy male nonsmokers, these results indicate that both the induction of theophylline metabolism by smoking and the inhibition of theophylline metabolism by cimetidine are preserved in old age.     

Smoking accelerates absorption of inhaled neutrophil elastase inhibitor FK706

PURPOSE: We compared the pharmacokinetics of the inhaled novel neutrophil elastase inhibitor FK706 between healthy nonsmokers and smokers. METHODS: Six healthy nonsmokers and six smokers inhaled 50 to 400 mg FK706 in two different doses. Series of plasma concentrations of the SSS form of FK706 (pharmacologically active epimer) were analyzed model dependently and independently. Pharmacokinetic parameters obtained from each group were compared after standardization by doses. RESULTS: The plasma concentration-time curve of inhaled FK706 was apparently different between smokers and nonsmokers. The maximum plasma concentrations (Cmax) were significantly higher in the smokers than in the nonsmokers (smokers, 1.47 +/- 0.62 ng/mL/mg; nonsmokers, 0.49 +/- 0.14 ng/mL/mg [mean +/- SD; P < .01]). The time to reach Cmax (tmax) and elimination half-life (t1/2) were statistically smaller in the smokers compared with the tmax and elimination t1/2 in the nonsmokers (tmax in smokers, 0.44 +/- 0.27 hours; tmax in nonsmokers, 1.17 +/- 0.39 hours [P < .01]; t1/2 in smokers, 1.23 +/- 0.40 hours; t1/2 in nonsmokers, 2.73 +/- 0.57 hours [P < .01]). The area under the plasma concentration-time curve and plasma clearance were not significantly different between the two groups. Model-dependent pharmacokinetic analysis, assuming a flip-flop model, revealed that the absorption rate constant (ka) was about 10 times greater in smokers than the ka in nonsmokers. CONCLUSION: Significant increases of Cmax and ka and reductions of tmax and elimination t1/2 of the inhaled FK706 were observed in the healthy smokers, suggesting that the smoking habit accelerates the drug absorption after inhalation. These results suggest that we should pay attention to the drug-related adverse events caused by smoking, especially when the drug has a narrow therapeutic range.     

Deficiency of vitamin E in the alveolar fluid of cigarette smokers. Influence on alveolar macrophage cytotoxicity.

Cigarette smoking produces oxidant-mediated changes in the lung important to the pathogenesis of emphysema. Since vitamin E can neutralize reactive oxygen species and prevent peroxidation of unsaturated lipids, it may constitute an important component of the lung's defense against oxidant injury. To better characterize the antioxidant protective role of vitamin E, young asymptomatic smokers and nonsmokers were evaluated by bronchoalveolar lavage before and immediately after a 3-wk course of oral vitamin E (2,400 IU/d). Smoker alveolar fluid at baseline was relatively deficient in vitamin E compared with nonsmoker fluid (3.1 +/- 0.7 ng/ml vs. 20.7 +/- 2.4 ng/ml, P less than 0.005). Although smoker alveolar fluid vitamin E levels increased to 9.3 +/- 2.3 ng/ml after supplementation, the levels remained significantly lower than nonsmoker baseline levels (P less than 0.01). This deficiency was explained, in part, by the increased oxidative metabolism of vitamin E to the quinone form in the lungs of smokers compared with nonsmokers. Although the significance of a lower concentration of alveolar fluid vitamin E is unclear, it may compromise the antioxidant protection afforded by the alveolar fluid as it coats the lung's epithelial surface. The protective role of vitamin E was assessed by cytotoxicity experiments, which demonstrated that the killing of normal rat lung parenchymal cells by smoker alveolar macrophages was inversely related to the vitamin E content of the parenchymal cells. These findings suggest that vitamin E may be an important lower respiratory tract antioxidant, and that the deficiency seen in young smokers may predispose them to an enhanced oxidant attack on their lung parenchymal cells.     

Tai Chi Improves Oxidative Stress Response and DNA Damage/Repair in Young Sedentary Females

[Purpose] This study was to examine the effects of 12 weeks of Tai Chi (TC) exercise on antioxidant capacity, and DNA damage/repair in young females who did not perform regular physical exercise. [Subjects and Methods] Ten female students from a Chinese university voluntarily participated in this program. All of them practiced the 24-form simplified Tai Chi, 5 times weekly, for 12 weeks. Plasma levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), glutathione (GSH), hydroxyl radical inhibiting capacity (OH·-IC), 8-hydroxy-2’-deoxyguanosine (8-OHdG), and 8-oxoguanine DNA glycosylase (OGG1) were measured at 0, 8, and 12 weeks. Heart rate (HR) was monitored during the last set of the training session at 4, 8, and 12 weeks. [Results] Plasma SOD and OH·-IC levels were increased at 8 and 12 weeks compared to the baseline (0 weeks). Gpx and GSH levels did not change significantly throughout the study period. The plasma MDA level was decreased significantly at 8 weeks but not at 12 weeks compared to the baseline value. While the plasma 8-OHdG level did not change throughout the study period, the plasma OGG1 level was significantly increased at 8 and 12 weeks compared to the baseline value. [Conclusion] TC practice for 12 weeks efficiently improved the oxidative stress response in young females who did not perform regular physical exercise. The TC exercise also increased the DNA repairing capacity.Key words: Tai Chi, Oxidative stress, DNA damage     

Effect of rosuvastatin on concentrations of plasma lipids, urine and plasma oxidative stress markers, and plasma high-sensitivity C-reactive protein in hypercholesterolemic patients with and without type 2 diabetes mellitus: A 12-week, open-label, pilot study

Background: Oxidative stress and inflammation of the arterial wall are now recognized as important factors in the progression of atherosclerosis. C-reactive protein (CRP) has been defined as a sensitive but not specific marker of inflammation. Statin therapy has been reported to decrease plasma high-sensitivity CRP (hs-CRP) concentration in hypercholesterolemic patients.Objective: The aim of this study was to examine the effect of rosuvastatin on concentrations of plasma lipids, urine and plasma oxidative stress markers, and plasma hs-CRP in hypercholesterolemic patients with and without type 2 diabetes mellitus.Methods: Patients with hypercholesterolemia with and without type 2 diabetes mellitus were enrolled in this pilot study after written informed consent was given. At baseline and after 12 weeks of open-label treatment with rosuvastatin 2.5 mg/d, concentrations of plasma lipids, urine and plasma oxidative stress markers, and plasma hs-CRP were measured. Urine 8-iso-prostaglandin F_2α (8-iso-PGF_2α) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) concentrations were also measured to asess whole-body oxidative stress. Plasma free-radical generation was estimated using a total reactive oxygen species (TROS) assay system. Adverse effects were assessed at each study visit (4-week intervals) through patient interviews and laboratory testing.Results: Thirty-five patients were enrolled with 1 dropping out prior to study completion; therefore, 34 patients (19 women, 15 men; mean [SE] age, 55.4 [13.6] years; range, 30–78 years) completed the study. Compared with baseline, significant decreases were found in serum concentrations of total cholesterol (TC) (252.3 [39.3] vs 187.8 [30.1] mg/dL; P < 0.001; Δ = 24.5%), LDL-C (162.0 [44.3] vs 98.5 [31.9] mg/dL; P < 0.001; Δ = 38.7%), and triglycerides (TG) (157.2 [93.6] vs 124.4 [69.9] mg/dL; P < 0.05; Δ = 11.7%) after 12 weeks of treatment with rosuvastatin. Serum HDL-C concentration did not change significantly from baseline (59.7 [20.5] vs 63.7 [19.3] mg/dL; Δ = 9.4%). The plasma LDL-C/HDL-C ratio decreased significantly after rosuvastatin treatment (3.03 [1.33] vs 1.72 [0.83]; P < 0.001; Δ = 43.2%). Compared with baseline, significant decreases were observed in urine concentrations of the oxidative stress markers after 12 weeks of rosuvastatin treatment: 8-iso-PGF_2α (342.8 [154.3] vs 300.6 [101.2] pg/mg; P < 0.05) and 8-OHdG (11.1 [4.53] vs 8.1 [2.7] ng/mg; P < 0.01). TROS decreased significantly (182.3 [29.0] vs 157.6 [17.3] U; P < 0.001), and plasma hs-CRP concentration also decreased significantly (0.107 [0.100] vs 0.054 [0.033] mg/dL; P < 0.05). When the patients' results were assessed according to the presence or absence of type 2 diabetes mellitus, urine 8-iso-PGF_2α concentration was significantly decreased from baseline only in the nondiabetic group. No adverse events were reported or observed during the course of the study.Conclusion: Rosuvastatin treatment was associated with significant reductions in plasma concentrations of TC, LDL-C, and TG, urine and plasma oxidative stress markers, and plasma hs-CRP in these hypercholesterolemic patients.     

Basal and exercise-induced changes in plasma catecholamines: relationship to age,smoking habits and sampling times

Summary. Contrary to earlier investigations, we have previously shown that the initial increase in venous plasma noradrenaline (NA) during exercise did not differ in young and elderly non-smoking subjects exercising at the same relative workload (75%), and that the greatest increase at maximal workload was observed in the young subjects. In order to determine whether the observed discrepancy could be explained by long-term smoking, plasma NA and adrenaline (A) were evaluated in eight elderly male smokers (mean age 67 years). The results were compared with data reported previously [Jensen et al. (1994) Exercise-induced changes in plasma catecholames and neuropeptide Y: relation to age and sampling times. J Appl Physiol, 76, 1269–1273] in seven young (mean age 27 years) and seven elderly (mean age 61 years) non-smoking male subjects. As shown earlier, basal plasma NA was significantly increased in elderly smokers compared to young and elderly non-smokers. During exercise at 75% of maximal work capacity, no difference was observed between elderly smokers and non-smokers. No difference in plasma A was found between elderly smokers and non-smokers either at rest or during exercise. These findings indicate that the exercise-induced increase in plasma NA did not differ in elderly smokers and non-smokers despite increased resting levels in the former group, and that the increase in the elderly subjects was not augmented compared to that in young subjects.