Passive smoke exposure induces oxidative damage in brains of rat pups: Protective role of diphenyl diselenide

The protective effect of diphenyl diselenide, (PhSe)₂, on oxidative stress induced by cigarette smoke exposure in brains of rat pups was evaluated. Animals were exposed to passive cigarette smoke (15?min/day) in two different experimental protocols: P1 (1, 2, and 3 cigarettes) and P2 (4, 5, and 6 cigarettes) for 3 weeks. Before each period of smoke exposure, animals received an oral administration of (PhSe)₂ (0.5?mg/kg). A number of toxicological parameters in the brain were examined, such as lipid peroxidation, δ-aminolevulinate dehydratase (δ-ALA-D) activity, and components of enzymatic (superoxide dismutase and catalase activities) and non-enzymatic antioxidant defenses (ascorbic acid and non-protein thiol levels). In P1, smoke exposure induced an inhibition of catalase activity and an increase of ascorbic acid levels. (PhSe)₂ treatment was able to protect catalase activity but not ascorbic acid levels. In P2, an augmentation of lipid peroxidation, a reduction of enzymatic and non-enzymatic antioxidant status, and an inhibition of δ-ALA-D activity caused by smoke exposure were found. (PhSe)₂ protected the brains of rat pups against oxidative damage induced by smoke exposure. The results are consistent with the antioxidant effect of (PhSe)₂ demonstrated by the reduction of oxidative changes caused by smoke exposure in the brains of pups.     

Histopathology,Urine Mutacenicity,and Bone Marrow Cytocenetics of Mice Exposed Nose-Only to Smoke from Cigarettes that Burn or Heat Tobacco

Abstract

Male and female B6C3F₁ mice were exposed nose-only to smoke from a test cigarette that heats tobacco, or from a reference cigarette that burns tobacco. Cigarette smoke was generated by a smoking machine, and the concentrations of wet total particulate matter (WTPM) were adjusted to 0, 0.16, 0.32, or 0.64 mg/l. Exposures were performed 1 h/day for 14 consecutive days. Urine mutagenicity was assessed by a modified Ames bacterial assay Clastogenesis (sister-chromatid exchanges, chromosome aberrations, and micronuclei) was evaluated in bone marrow cells. Respiratory rate was depressed significantly by exposure to smoke from the reference cigarette, but not the test. Blood carboxyhemoglobin, plasma nicotine, and plasma cotinine showed exposure-dependent increases in the smoke-exposed animals. Histopathological changes similar to those noted previously in smoke-exposed rats were noted, with fewer and less pronounced changes in the animals exposed to smoke from the test cigarette when compared with the reference. Positive urine mutagenicity and clastogenic responses were observed in the animals treated with positive control chemicals. However the urine mutagenicity and clastogenic responses of smoke-exposed animals (both cigarette types) were not different from those of sham-exposed animals, except for the micronucleus assay where animals exposed to high concentrations of reference cigarette smoke showed a significant increase over controls.     

The disruption of L-carnitine metabolism by aluminum toxicity and oxidative stress promotes dyslipidemia in human astrocytic and hepatic cells

l-Carnitine is a critical metabolite indispensable for the metabolism of lipids as it facilitates fatty acid transport into the mitochondrion where β-oxidation occurs. Human astrocytes (CCF-STTG1 cells) and hepatocytes (HepG2 cells) exposed to aluminum (Al) and hydrogen peroxide (H₂O₂), were characterized with lower levels of l-carnitine, diminished β-oxidation, and increased lipid accumulation compared to the controls. γ-Butyrobetainealdehyde dehydrogenase (BADH) and butyrobetaine dioxygenase (BBDOX), two key enzymes mediating the biogenesis of l-carnitine, were sharply reduced during Al and H₂O₂ challenge. Exposure of the Al and H₂O₂-treated cells to α-ketoglutarate (KG), led to the recovery of l-carnitine production with the concomitant reduction in ROS levels. It appears that the channeling of KG to combat oxidative stress results in decreased l-carnitine synthesis, an event that contributes to the dyslipidemia observed during Al and H₂O₂ insults in these mammalian cells. Hence, KG may help alleviate pathological conditions induced by oxidative stress.     

Icaritin inhibits oxidative stress in murine astrocytes by binding to Orai1 to block store-operated calcium channel

Previous study has shown that icaritin (ICT) has meaningful protective effect on cerebral ischemic stroke, and this study aimed to investigate its mechanism from the aspect of protecting astrocytes from oxidative stress. Murine primary astrocytes were pretreated by ICT and exposed to H₂O₂ to induce oxidative stress. The results indicated that ICT inhibited H₂O₂-induced astrocytes apoptosis, decreased Bax and cleaved caspase-3, and increased Bcl-2. In addition, ICT inhibited H₂O₂-induced oxidative stress, increased mitochondrial membrane potential (ΔΨ_m), and maintained mitochondrial morphology. ICT decreased the synthesis of malondialdehyde and increased the activity of glutathione peroxidase, catalase, and superoxide dismutase. Moreover, ICT suppressed the transient and resting intracellular Ca²⁺ overload. Further investigation revealed that ICT could target the combination with Orai1 to block store-operated calcium channel induced by H₂O₂. However, ICT did not enhance the protective effect of RO2959, a selective blocker of Orai1. These results indicate that ICT can play a neuroprotective role against oxidative stress injury by binding to Orai1 to block SOCC.     

Angiotensin II type 1 receptor blockade suppresses H2O2-induced retinal degeneration in photoreceptor cells

Exposure to reactive oxygen species (ROS) leads to the development and progression of retinal degenerative diseases. However, the exact mechanisms are not fully understood. In this article, the role of angiotensin II type 1 receptor (AT1R) signaling in H₂O₂-induced retinal damage was examined. Mouse photoreceptor-derived 661?W cells were treated with the AT1R blockers valsartan, losartan and candesartan before exposure to H₂O₂. Cell viability, intracellular ROS level, mitochondrial membrane potential (MMP), cytochrome-c level, DNA fragmentation, caspase activity and gene expression were detected. Pre-treatment of 661?W cells with AT1R blockers significantly decreased H₂O₂-mediated toxicity and reduced the ROS level. In addition, apoptosis-related biochemical indicators showed that pre-incubation of AT1R blockers would elevate the MMP, decrease the release of cytochrome-c and formation of DNA fragmentation, and inhibit activities of caspase-3 and caspase-9 in exogenous H₂O₂-treated 661?W cells. Moreover, treatment with AT1R blockers suppressed the expression of Egr1, Fosl1 and Lox12. These results suggest that AT1R signaling mediates H₂O₂-induced apoptosis, at least partially through generating the ROS and increasing the levels of proapoptotic molecules in 661?W cells. AT1R blockade may provide a new therapeutic approach for preventing oxidative stress-induced retinal neural damage.     

Antioxidant ameliorating effects against H2O2-induced cytotoxicity in primary endometrial cells

Oxidative stress and a disrupted antioxidant system are involved in a variety of pregnancy complications. In the present study, the role of vitamin E (Vit E) and folate as radical scavengers on the GSH homeostasis in stress oxidative induced in rat endometrial cells was investigated. Primary endometrial stromal cell cultures treated with 50 and 200?µM of H₂O₂ and evaluated the cytoprotective effects of Vit E (5?µM) and folate (0.01?µM) in H₂O₂-treated cells for 24?h. Following the exposure of endometrial cells to H₂O₂ alone and in the presence of Vit E and/or folate, cell survival, glutathione peroxidase (GPx) and glutathione reductase activities and the level of reduced glutathione (GSH) were measured. Cell adhesions comprise of cell attachment and spreading on collagen were determined. Flow cytometric analysis using annexin V was used to measure apoptosis. H₂O₂ treatment showed a marked decrease in cell viability, GPx and GR activities and the level of GSH. Although Vit E or folate had some protective effect, combination therapy with Vit E and folate attenuated all the changes due to H₂O₂ toxicity. An increasing number of alive cells was showed in the cells exposed to H₂O₂ (50?µM) accompanied by co-treatment with Vit E and folic acid. The present findings indicate that co-administration of Vit E and folate before and during pregnancy may maintain a viable pregnancy and contribute to its clinical efficacy for the treatment of some idiopathic infertility.     

Nitrogen Dioxide Exposure Attenuates Cigarette Smoke-Induced Cytokine Production in Mice

Cigarette smoke is the most important cause for the development of chronic obstructive pulmonary disease (COPD). Since only a minority of smokers and some nonsmokers develop COPD, other factors must be involved as well. NO₂ is an important air pollutant associated with respiratory symptoms in humans and emphysema development in animal models. We hypothesized that combined exposure to NO₂ and cigarette smoke will enhance pulmonary inflammation and emphysema development. Mice were exposed to 20 ppm NO₂ for 17 h/day, to 24 puffs of cigarette smoke 2 times per day, to their combination, or to control air for 5 days/wk during 4 wk. Following the last NO₂ exposure and within 24 h after the last smoke exposure the mice were sacrificed. Lungs were removed and analyzed for several inflammatory parameters and emphysema. Cigarette smoke exposure increased eosinophil numbers and levels of tumor necrosis factor (TNF)-α, KC, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-6. NO₂ exposure increased goblet cells, eosinophils, and the levels of IL-6, while it decreased the levels of IL-10. Four weeks of NO₂, cigarette smoke, or their combination was not sufficient to induce significant emphysema, nor did it lead to increased numbers of lymphocytes, neutrophils, or macrophages in lung tissue. Instead, NO₂ exposure attenuated the smoke-induced increases in levels of TNF-α, KC, and MCP-1. These dampening effects of NO₂ may be due to modulating effects of NO₂ on cytokine production by macrophages and epithelial cells, which have been reported earlier. The next step is to translate these findings of combined, controlled exposure in animals to the human situation.     

In vitro effect of vanadyl sulfate on cultured primary astrocytes: cell viability and oxidative stress markers.

Exposure to vanadium has been associated with deleterious effects on the central nervous system in animals and humans. Although vanadium-derived pro-oxidant species were reported to be involved in vanadium-mediated neurotoxicity, the ability of this metal to induce oxidative stress markers in glial cells remains to be elucidated. In this study, we investigated the cytotoxicity and the generation of reactive oxygen species (ROS) and nitric oxide (NO) by mouse primary astrocytes after treatment with vanadyl sulfate (VOSO₄) at concentrations of 20, 50, 100, 200, and 500 μM. The resazurin assay revealed that treatment with VOSO₄ for 24 and 48 h at concentrations of 50 and 100 μM, respectively, or higher substantially induced astrocytic cytotoxicity. Intracellular ROS increased after 6-h exposure to the lowest concentration tested (20 μM VOSO₄) and tended to intensify after 24- and 48-h treatments reaching significant values for 20 and 500 μM VOSO₄. In turn, NO production in the examined cells was elevated after exposure to all concentrations at the 6-, 24-, and 48-h incubation periods. Our study demonstrated the ability of VOSO₄ to induce H₂O₂ generation in cell-free DMEM/F12 medium. The H₂O₂ levels were in the micromolar range (up to 5 μM) and were detected mostly during the first few minutes after VOSO₄ addition, suggesting that the generated H₂O₂ could not induce toxic effects on the cells. Taken together, these results show VOSO₄ induced cytotoxicity in primary astrocyte cells, which may have resulted from vanadyl-stimulated intracellular ROS and NO generation in these cells.     

Evidence for cigarette smoke-induced oxidative stress in the rat pancreas

Background/aims: Recent findings with a rodent model of cigarette smoke inhalation revealed a causal relationship between chronic exposure to cigarette smoke and the development of pancreatitis. The present study was conducted to ascertain whether cigarette smoke induces oxidative stress in the rat pancreas concurrently with inflammation.

Methodology: Rats (six per treatment group) were treated for 0, 3, 6, 9, or 12 weeks with cigarette smoke (0.7?mg/L). Pancreatic tissues were examined for histological and pathological alterations and serum for changes in interleukin-6 concentration. Pancreatic expression and localization of α-smooth muscle actin, transforming growth factor-β1, and collagen-1 were determined as measures of progressive inflammation/fibrosis. Pancreatic superoxide dismutase and glutathione peroxidase activities and malondialdehyde content were measured as indices of oxidative stress.

Results: Inflammatory cell infiltration and ductal hyperplasia were detected in pancreata after 12 weeks of treatment with cigarette smoke. The serum interleukin-6 concentration increased significantly and pancreatic glutathione peroxidase activity declined significantly after 12 weeks of treatment. No other significant changes were observed.

Conclusions: Pancreata of rats exposed chronically to cigarette smoke exhibit inflammation concurrently with suppression of glutathione peroxidase activity. These observations favor a role for oxidative stress in the induction of pancreatitis associated with chronic cigarette smoke inhalation.     

In vivo genotoxicity evaluation of lung cells from Fischer 344 rats following 28 days of inhalation exposure to MWCNTs,plus 28 days and 90 days post-exposure

Abstract

Despite their useful physico-chemical properties, carbon nanotubes (CNTs) continue to cause concern over occupational and human health due to their structural similarity to asbestos. Thus, to evaluate the toxic and genotoxic effect of multi-wall carbon nanotubes (MWCNTs) on lung cells in vivo, eight-week-old rats were divided into four groups (each group?=?25 animals), a fresh air control (0?mg/m³), low (0.17?mg/m³), middle (0.49?mg/m³), and high (0.96?mg/m³) dose group, and exposed to MWCNTs via nose-only inhalation 6?h per day, 5 days per week for 28 days. The count median length and geometric standard deviation for the MWCNTs determined by TEM were 330.18 and 1.72?nm, respectively, and the MWCNT diameters ranged from 10 to 15?nm. Lung cells were isolated from five male and five female rats in each group on day 0, day 28 (only from males) and day 90 following the 28-day exposure. The total number of animals used was 15 male and 10 female rats for each concentration group. To determine the genotoxicity of the MWCNTs, a single cell gel electrophoresis assay (Comet assay) was conducted on the rat lung cells. As a result of the exposure, the olive tail moments were found to be significantly higher (p?<?0.05) in the male and female rats from all the exposed groups when compared with the fresh air control. In addition, the high-dose exposed male and middle and high-dose exposed female rats retained DNA damage, even 90 days post-exposure (p?<?0.05). To investigate the mode of genotoxicity, the intracellular reactive oxygen species (ROS) levels and inflammatory cytokine levels (TNF-α, TGF- β, IL-1, IL-2, IL-4, IL-5, IL-10, IL-12 and IFN-γ) were also measured. For the male rats, the H₂O₂ levels were significantly higher in the middle (0 days post-exposure) and high- (0 days and 28 days post-exposure) dose groups (p?<?0.05). Conversely, the female rats showed no changes in the H₂O₂ levels. The inflammatory cytokine levels in the bronchoalveolar lavage (BAL) fluid did not show any statistically significant difference. Interestingly, the short-length MWCNTs deposited in the lung cells were persistent at 90 days post-exposure. Thus, exposing lung cells to MWCNTs with a short tube length may induce genotoxicity.     

Toxicity of zinc oxide (ZnO) nanoparticles on human bronchial epithelial cells (BEAS-2B) is accentuated by oxidative stress

Although several studies reported that cytotoxic effects of various nanoparticles are partially due to induction of oxidative stress, it is unclear how oxidative state of the cell per se could influence its sensitivity to cytotoxic nanoparticles. This is of clinical significance because certain pathological conditions such as inflammation is associated with elevated oxidative stress and this may alter sensitivity of cells and tissues to cytotoxic nanoparticles. Hence, this study investigated how initial exposure of BEAS-2B human bronchial epithelial cells to oxidative stress influences subsequent response to cytotoxic challenge with zinc oxide (ZnO) nanoparticles (≈10 nm). Oxidative stress was induced by exposing BEAS-2B cells to 5 and 10 μM of H₂O₂ for 45 min in PBS (with Ca²⁺). Subsequently, the H₂O₂ solutions were washed off and the cells were exposed to varying concentrations (5–25 μg/ml) of ZnO nanoparticles in culture media for 24 h, followed by cell viability assessment with the WST-8 assay. The results demonstrated that initial transient exposure of cells to oxidative stress accentuated cytotoxicity of ZnO nanoparticles. In the negative control unexposed to H₂O₂, >99% of cells remained viable up to a ZnO nanoparticle concentration of 10 μg/ml, but displayed a steep decrease in viability above 10 μg/ml ZnO. By contrast, cells that were initially exposed to 5 and 10 μM of H₂O₂, displayed a sharp drop in viability even at concentrations below 10 μg/ml ZnO. At 10 μg/ml ZnO, cells initially exposed to 10 μM H₂O₂ displayed a viability of 40.6 ± 2.0%, which is significantly lower than the corresponding values of 72.8 ± 2.0% and 99.9 ± 1.1% obtained for initial exposure to 5 μM H₂O₂ and the negative control, respectively. Hence, initial exposure of BEAS-2B cells to oxidative stress sensitized their subsequent response to cytotoxic challenge with ZnO nanoparticles.     

Oxidative stress-induced aberrant G9a activation disturbs RE-1-containing neuron-specific genes expression,leading to degeneration in human SH-SY5Y neuroblastoma cells

Oxidative stress-induced neurodegeneration is one of several etiologies underlying neurodegenerative disease. In the present study, we investigated the functional role of histone methyltransferase G9a in oxidative stress-induced degeneration in human SH-SY5Y neuroblastoma cells. Cell viability significantly decreased on H₂O₂ treatment; however, treatment with the G9a inhibitor BIX01294 partially attenuated this effect. The expression of neuron-specific genes also decreased in H₂O₂-treated cells; however, it recovered on G9a inhibition. H₂O₂-treated cells showed high levels of H3K9me2 (histone H3 demethylated at the lysine 9 residue), which is produced by G9a activation; BIX01294 treatment reduced aberrant activation of G9a. H3K9me2 occupancy of the RE-1 site in neuron-specific genes was significantly increased in H₂O₂-treated cells, whereas it was decreased in BIX01294-treated cells. The differentiation of H₂O₂-treated cells also recovered on G9a inhibition by BIX01294. Consistent results were observed when used another G9a inhibitor UCN0321. These results demonstrate that oxidative stress induces aberrant activation of G9a, which disturbs the expression of neuron-specific genes and progressively mediates neuronal cell death. Moreover, a G9a inhibitor can lessen aberrant G9a activity and prevent neuronal damage. G9a inhibition may therefore contribute to the prevention of oxidative stress-induced neurodegeneration.     

The genotoxic effect of nicotine on chromosomes of human fetal cells: The first report described as an important study

Context: Recent studies have suggested a direct contribution of nicotine ? the addictive component of tobacco and tobacco smoke ? to human carcinogenesis, and it remains the most common harmful substance to which pregnant women are exposed. Also, it has deleterious effects on the fetus. The sperm of smoking fathers and newborns of smoking mothers have elevated frequencies of chromosome translocations and DNA strand breaks.

Objective: We tried to understand the genotoxic effect of nicotine in pregnancies of active or passive smoking mothers. For this reason, we provide the evidence that nicotine exposure in vitro has detrimental effects on fetal cells.

Materials and methods: We examined the effect of nicotine sulphate on amniotic cells by designing an experimental setting consisting fetal cells grown in nicotine containing medium (25?ng/mL) in study group and fetal cells grown in control medium, which did not contain nicotine.

Results: According to our findings, there is a significant difference of chromosomal aberrations (CAs) between nicotine containing medium grown cells and control medium grown cells, determined by the χ2 test (P <0.001). We found CAs in 21.5% of cells analyzed. The 19.4% of the all cells had numerical aberrations. Chromosomes 21, 22, 8, 15 and 20 related numerical abnormalities were found to be the most frequent numerical abnormalities.

Conclusion: Results of this study confirm that the nicotine leads to significant direct genotoxic effects in human fetal cells in vitro. We speculate that there is an association between prenatal exposure to cigarette smoke and in utero aneuploidies.     

Persistent hexavalent chromium exposure impaired the pubertal development and ovarian histoarchitecture in wistar rat offspring

Hexavalent chromium (CrVI) is a highly toxic metal and a major environmental pollutant. Several studies indicate that CrVI exposure adversely affects reproductive function. We reported that maternal Cr exposure resulted in Cr accumulation in the reproductive organs of female offsprings. CrVI can cross the placental barrier and also can be passed through breastfeeding. The present investigation aimed to determine the persistent (in utero through puberal period) CrVI exposure‐induced toxic effects on the reproductive functions of mother and the offspring. Induction of oxidative stress is one of the plausible mechanisms behind Cr‐induced cellular deteriorations. Mother rats exposed to CrVI showed reduced reproductive outcome, while the offsprings showed higher accumulation of Cr in ovary, altered steroid, and peptide hormones. Specific activities of antioxidant enzymes were decreased and associated with increased levels of H₂O₂, and lipid peroxidation. CrVI exposure also damaged the ovarian histoarchitecture in various age groups studied. CrVI exposure also delayed the sexual maturation. Results from the present investigation suggest that CrVI exposure from in utero through puberal period significantly damaged the pubertal development through altered antioxidants, anemia, and altered hormone levels. These changes were associated with damaged ovarian histoarchitecture and extended estrous cycle in developing Wistar rats. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 814–828, 2014.     

A novel macrolide/fluoroketolide,solithromycin (CEM-101), reverses corticosteroid insensitivity via phosphoinositide 3-kinase pathway inhibition

Background and Purpose

Corticosteroid insensitivity is a major therapeutic problem for some inflammatory diseases including chronic obstructive pulmonary disease (COPD), and it is known to be induced by reduced histone deacetylase (HDAC)-2 activities via activation of the phosphoinositide 3-kinase (PI3K) pathway. The aim of this study is to evaluate effects of a novel macrolide/fluoroketolide, solithromycin (SOL, CEM-101), on corticosteroid sensitivity induced by oxidative stress.

Experimental Approach

Corticosteroid sensitivity was determined by IC₅₀/EC₅₀ of dexamethasone (Dex) on TNF-α-induced CXCL8 production in U937 monocytic cell line and peripheral blood mononuclear cells (PBMC) from COPD patients. Activities of HDAC and protein phosphatase 2A (PP2A) were measured by fluorescence-based assay in cells exposed to hydrogen peroxide (H₂O₂). We also investigated steroid insensitive airway neutrophilia in cigarette smoke exposed mice in vivo.

Key Results

SOL (10 μM) restored Dex sensitivity in PBMC from COPD patients, H₂O₂-treated U937 cells and phorbol 12-myristate 13-acetate-differentiated U937 cells. In addition, SOL restored HDAC activity with concomitant inhibition of Akt phosphorylation as surrogate marker of PI3K activation. The inhibition of Akt phosphorylation by SOL was due to increased PP2A phosphatase activity, which was reduced in COPD and oxidative stress model. Other known macrolides, such as eryhthromycin, clarithromycin and azithromycin, were significantly less effective in these responses. In cigarette smoke-exposed mice, SOL (100 mg kg⁻¹, po) showed significant but weak inhibition of neutrophilia, whereas Dex (10 mg kg⁻¹, p.o.) showed no such effect. However, a combination of SOL and Dex inhibited neutrophilia by over 50%.

Conclusions and Implications

SOL has potential as novel therapy for corticosteroid-insensitive diseases such as COPD.     

Free lung cell response after combined exposure to cigarette smoke and industrial dusts

Guinea pigs were acutely exposed to different airborne dusts and freshly generated cigarette smoke. The effect was evaluated by counting the number of free lung cells using a lavage method. An exposure to MnO₂ and smoke on the same day caused an increase in the number of leukocytes 24 h thereafter.By increasing the time interval between the MnO₂ and smoke exposure, the effect gradually disappeared. Al₂O₃ or SiO₂ also caused an increase in the number of leukocytes, whereas TiO₂ had no effect. The pathogenesis behind the reaction and the epidemiological implications are discussed.     

Brain and lungs of rats are differently affected by cigarette smoke exposure: Antioxidant effect of an organoselenium compound

Cigarette smoke exposure has been associated with oxidative stress in several organs. Antioxidant effect of diphenyl diselenide (PhSe)₂, an organoselenium compound, on oxidative damage induced by sub-chronic cigarette smoke exposure in brain and lungs of rats was investigated. Animals were exposed 5 times/week to one, two, three and four cigarettes for exposure periods of 15 min during the first, second, third and fourth weeks. Reactive species (RS) levels, enzymatic antioxidant defenses (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activities) and non-enzymatic antioxidant defenses (ascorbic acid and non-protein thiol (NPSH) levels) were examined in brain and lungs of rats. An increase in RS levels induced by cigarette smoke in both tissues of rats was demonstrated. Cigarette smoke altered enzymatic antioxidant defenses (GST, CAT and SOD activities) in both tissues, and reduced the non-enzymatic antioxidant defenses in lungs. (PhSe)₂ (0.5 mg/kg/day, 5 times/week) restored RS levels and antioxidant defenses in brain of rats exposed to cigarette smoke. (PhSe)₂ treatment increased NPSH levels, GST and GR activities per se in lungs of rats. In conclusion, sub-chronic exposure to cigarette smoke caused alterations in antioxidant defense system and a tissue-specific oxidative stress in brain and lungs of rats. (PhSe)₂ restored antioxidant defenses in lungs and brain of rats.     

Pulmonary hypertension and vascular oxidative damage in cigarette smoke exposed eNOS−/− mice and human smokers

Context: Cigarette smoke is known to be associated with pulmonary hypertension in humans and in animal models. Although the etiology of pulmonary hypertension in smokers is not understood, recent work has suggested a role for inducible nitric oxide synthase (iNOS) in inducing oxidative stress.

Objective and Methods: To further evaluate this question, we assessed eNOS-/- mice exposed to air or cigarette smoke for the presence of pulmonary hypertension and examined vascular remodeling and expression of nitrotyrosine, a marker of reactive nitrogen species-induced oxidative damage, using immunohistochemistry. To ascertain whether oxidants may play a role in humans, we also examined lung tissue from nonsmokers, and patients with chronic obstructive pulmonary disease (COPD) with and without pulmonary hypertension.

Results: We found that eNOS^?/? mice developed increased pulmonary arterial pressure after six months cigarette smoke exposure, and this was associated with vascular remodeling and increased vascular nitrotyrosine staining. iNOS gene expression was decreased in the pulmonary arteries of the smoke exposed animals, and no protein was detectable by immunohistochemistry. In humans, vascular nitrotyrosine staining intensity was increased in smokers with COPD compared to nonsmokers, and further increased in smokers with combined COPD and pulmonary hypertension.

Conclusions: We conclude that cigarette smoke-induced pulmonary hypertension is associated with evidence of oxidative vascular damage by reactive nitrogen species, but that iNOS does not appear to be the major contributor to such damage. Most likely the source of reactive nitrogen species is the cigarette smoke itself.     

依达拉奉对H2O2致星形胶质细胞损伤的保护作用

目的:观察依达拉奉(EDA)对H2O2损伤后的星形胶质细胞活力的影响及其细胞内谷胱甘肽(GSH)含量、诱导型一氧化氮合酶(iNOS)表达的影响.方法:应用MTT法检测星形胶质细胞活力;Tietze法检测细胞内GSH含量;Western-blot法检测细胞内iNOS的表达.结果:H2O2作用24 h后可呈浓度依赖性地抑制星形胶质活力;EDA可逆转H2O2导致的星形胶质细胞活力的下降,胞内GSH含量的降低以及iNOS表达的增加.结论:EDA可改善H2O2所致的星形胶质细胞的氧化损伤.     

Acute exposure to waterpipe tobacco smoke induces changes in the oxidative and inflammatory markers in mouse lung

Context: Tobacco smoking represents a global public health threat, claiming approximately 5 million lives a year. Waterpipe tobacco use has become popular particularly among youth in the past decade, buttressed by the perception that the waterpipe “filters” the smoke, rendering it less harmful than cigarette smoke.

Objective: In this study, we examined the acute exposure of waterpipe smoking on lung inflammation and oxidative stress in mice, and compared that to cigarette smoking.

Materials and methods: Mice were divided into three groups; fresh air control, cigarette and waterpipe. Animals were exposed to fresh air, cigarette, or waterpipe smoke using whole body exposure system one hour daily for 7 days.

Results: Both cigarette and waterpipe smoke exposure resulted in elevation of total white blood cell count, as well as absolute count of neutrophils, macrophages, and lymphocytes (P < 0.01). Both exposures also elevated proinflammatory markers such as TNF-α and IL-6 in BALF (P < 0.05), and oxidative stress markers including GPx activity in lungs (P < 0.05). Moreover, waterpipe smoke increased catalase activity in the lung (P < 0.05). However, none of the treatments altered IL-10 levels.

Discussion and conclusion: Results of cigarette smoking confirmed previous finding. Waterpipe results indicate that, similar to cigarettes, exposure to waterpipe tobacco smoke is harmful to the lungs.