Biomedical subjects

K Donaldson

Publications and source records attributed to K Donaldson.

At least 37 records · Page 2Linked to original sources

PubMed2001

Ultrafine particles and nitrogen oxides generated by gas and electric cooking.

OBJECTIVES: To measure the concentrations of particles less than 100 nm diameter and of oxides of nitrogen generated by cooking with gas and electricity, to comment on possible hazards to health in poorly ventilated kitchens. METHODS: Experiments with gas and electric rings, grills, and ovens were used to compare different cooking procedures. Nitrogen oxides (NO(x)) were measured by a chemiluminescent ML9841A NO(x) analyser. A TSI 3934 scanning mobility particle sizer was used to measure average number concentration and size distribution of aerosols in the size range 10-500 nm. RESULTS: High concentrations of particles are generated by gas combustion, by frying, and by cooking of fatty foods. Electric rings and grills may also generate particles from their surfaces. In experiments where gas burning was the most important source of particles, most particles were in the size range 15-40 nm. When bacon was fried on the gas or electric rings the particles were of larger diameter, in the size range 50-100 nm. The smaller particles generated during experiments grew in size with time because of coagulation. Substantial concentrations of NO(X) were generated during cooking on gas; four rings for 15 minutes produced 5 minute peaks of about 1000 ppb nitrogen dioxide and about 2000 ppb nitric oxide. CONCLUSIONS: Cooking in a poorly ventilated kitchen may give rise to potentially toxic concentrations of numbers of particles. Very high concentrations of oxides of nitrogen may also be generated by gas cooking, and with no extraction and poor ventilation, may reach concentrations at which adverse health effects may be expected. Although respiratory effects of exposure to NO(x) might be anticipated, recent epidemiology suggests that cardiac effects cannot be excluded, and further investigation of this is desirable.

Air Pollution, Indoor↗

PubMed2001

Adenoviral E1A primes alveolar epithelial cells to PM(10)-induced transcription of interleukin-8.

The presence of the adenoviral early region 1A (E1A) protein in human lungs has been associated with an increased risk of chronic obstructive pulmonary disease (COPD), possibly by a mechanism involving amplification of proinflammatory responses. We hypothesize that enhanced inflammation results from increased transcription factor activation in E1A-carrying cells, which may afford susceptibility to environmental particulate matter < 10 microm (PM(10))-mediated oxidative stress. We measured interleukin (IL)-8 mRNA expression and protein release in human alveolar epithelial cells (A549) transfected with the E1A gene (E1A+ve). Both E1A+ve and -ve cells released IL-8 after incubation with TNF-alpha, but only E1A+ve cells were sensitive to LPS stimulation in IL-8 mRNA expression and protein release. E1A+ve cells showed an enhanced IL-8 mRNA and protein response after treatment with H(2)O(2) and PM(10). E1A-enhanced induction of IL-8 was accompanied by increases in activator protein-1 and nuclear factor-kappa B nuclear binding in E1A+ve cells, which also showed higher basal nuclear binding of these transcription factors. These data suggest that the presence of E1A primes the cell transcriptional machinery for oxidative stress signaling and therefore facilitates amplification of proinflammatory responses. By this mechanism, susceptibility to exacerbation of COPD in response to particulate air pollution may occur in individuals harboring E1A.

Adenovirus E1A Proteins↗

PubMed2001

Ambient particle inhalation and the cardiovascular system: potential mechanisms.

Well-documented air pollution episodes throughout recent history have led to deaths among individuals with cardiovascular and respiratory disease. Although the components of air pollution that cause the adverse health effects in these individuals are unknown, a small proportion by mass but a large proportion by number of the ambient air particles are ultrafine, i.e., less than 100 nm in diameter. This ultrafine component of particulate matter with a mass median aerodynamic diameter less than 10 microm (PM(10) may mediate some of the adverse health effects reported in epidemiologic studies and for which there is toxicologic evidence to support this contention. The exact mechanism by which ultrafine particles have adverse effects is unknown, but these particles have recently been shown to enhance calcium influx on contact with macrophages. Oxidative stress is also to be anticipated at the huge particle surface; this can be augmented by oxidants generated by recruited inflammatory leukocytes. Atheromatous plaques form in the coronary arteries and are major causes of morbidity and death associated epidemiologically with particulate air pollution. In populations exposed to air pollution episodes, blood viscosity, fibrinogen, and C-reactive protein (CRP) were higher. More recently, increases in heart rate in response to rising air pollution have been described and are most marked in individuals who have high blood viscosity. In our study of elderly individuals, there were significant rises in CRP, an index of inflammation. In this present review, we consider the likely interactions between the ultrafine particles the acute phase response and cardiovascular disease.

Acute Disease↗

PubMed2001

The quartz hazard: effects of surface and matrix on inflammogenic activity.

Modification of the quartz surface during the history of the particle is a powerful idea in understanding the variability of the quartz hazard. Interactions between quartz and other minerals are likely to occur in sediments, during industrial processing, or in matrix-bound quartz. We discuss new evidence regarding the basis of changes in the quartz surface that relate to changes in its ability to cause inflammation. Different samples of quartz were subjected to various biological assays. Endpoints included instillation of quartz into the tracheobronchial tree and measurement of PMN numbers in bronchoalveolar lavage (BAL) and in lung tissue, levels of the chemokine MIP-2 in BAL, and nuclear translocation of the transcription factor NF-kappaB in BAL cells. In vitro biological assays included cytotoxicity to epithelial cells, hemolytic activity, and radical activity of the particle surface as measured by electron spin resonance. Treatment of quartz with aluminium lactate impaired its ability to cause PMN recruitment, chemokine release, and NF-kappaB nuclear translocation in BAL. Workplace quartzes had no proinflammatory activity, which correlated with their ability to cause hemolysis but not their electron spin resonance (ESR) activity. Quartz in a matrix with coalmine dust or fly-ash showed different effects. In fly-ash, the toxicity was masked, but coalmine dusts were more toxic to epithelial cells than pure quartz in vitro; however, after instillation, the long-term inflammation was not related to the in vitro activity. Amelioration of quartz surface activity can occur in workplace samples of quartz and quartz samples whose surface is protected, to the extent that they have very little inflammogenic activity and display an inability to activate key subcellular pathways that lead to inflammation. Quartz from a workplace whose surface has been affected, or in a matrix such as coalmine dust or fly-ash, can have its toxicity modulated. These effects are due to minerals and organic compounds that can both decrease (e.g., aluminium salts) or enhance (e.g., coalmine dust matrix) biological activity and thus may contribute to toxicity in a complex way that is not easily predicted. Iron is a good example. There are reports that it can enhance quartz toxicity, or it may have little role to play in its toxicity, as shown here for almost pure quartz particles. A broad program of further research is needed before we have a sound understanding of the mechanisms of quartz toxicity.

Air Pollutants, Occupational↗

PubMed2001

The accessibility of computer-based health information for patients: kiosks and the web.

The Internet is a rich source of health information but it is not as accessible as many claim. This paper brings together three projects to illustrate technical and cost barriers and some options to overcome them. (1) A survey amongst a representative sample of 180 patients in rural Spain showed a marked age gradient in computer access. None over the age of 50 had, and less than 10% planned, access to the Internet whereas a quarter were prepared to use health centre based touchscreen kiosks. (2) Half the commonly used search engines did not include the two most relevant websites for Glasgow colorectal cancer patients in the first ten documents listed, showing the difficulty facing patients in finding relevant information. Selection of information would help patients avoid being overwhelmed with information. (3) One method to improve accessibility is to download websites to kiosks but two projects showed that considerable work is required to reformat the information. Public access computing, such as kiosks, could help make the Internet more accessible. We discuss whether Web sites which structure their information according to method of access, place and person provide a way forward.

Age Factors↗

PubMed2000

Persistent depletion of I kappa B alpha and interleukin-8 expression in human pulmonary epithelial cells exposed to quartz particles.

Chronic inflammation and fibrosis following quartz inhalation has been associated with persistent up-regulation of several "pro-inflammatory" genes, which are commonly regulated by nuclear factor kappa-B (NF-kappaB). Transcription of the NF-kappaB-inhibitor IkappaBalpha is also under NF-kappaB control, and its de novo synthesis is considered to comprise a negative feedback loop in transient inflammation. To investigate this mechanism in particle inflammation, we have studied IkappaBalpha degradation in A549 cells exposed to DQ12-quartz or TiO(2), in relation to the expression of IL-8. Although both quartz and TiO(2) were found to cause IkappaBalpha degradation, only quartz elicited a mild IkappaBalpha depletion, first appearing at 4 h. TiO(2) was found to cause a higher short-term increase in IkappaBalpha mRNA-expression compared to quartz, whereas the early enhancement of IL-8 expression and release was similar for both particles. Up-regulation of IL-8 expression was found to persist with quartz only. Cotreatment with PDTC and curcumin reduced particle-elicited IL-8 response, whereas cycloheximide caused enhancement of IL-8 mRNA expression in both the quartz- and TiO(2)-treated cells. Our results demonstrate that mineral dusts cause IkappaBalpha degradation, a transient increase in de novo synthesis of IkappaBalpha, and enhanced IL-8 expression in human pulmonary epithelial cells. While IkappaBalpha degradation and early IL-8 expression seem to be general particle phenomena, particle-specific characteristics impact on activation of IkappaBalpha gene transcription, apparently accounting for the different proinflammatory IL-8 responses seen with quartz and TiO(2) in the longer term. These observations may provide an explanation for the transient versus the persistent pulmonary inflammatory status and subsequent differences in pathogenic potency of TiO(2) and quartz.

Blotting, Western↗

PubMed2000

Activation of NF-kappaB by PM(10) occurs via an iron-mediated mechanism in the absence of IkappaB degradation.

Exposure to particulate air pollution (PM(10)) is associated with exacerbations of respiratory diseases and increased cardiopulmonary mortality. PM(10) induces lung inflammation in rats, which has been attributed to many factors, including the ultrafine components of PM(10), endotoxins, and transition metals. In this study, we investigated in alveolar epithelial (A549) cells whether PM(10) could activate nuclear factor-kappa B (NF-kappaB), a transcription factor stimulated in response to many proinflammatory agents. Our results show that PM(10) samples from various sites within the United Kingdom cause nuclear translocation, DNA-binding, and transcriptional activation of NF-kappaB in A549 cells. Furthermore, increased NF-kappaB activity was observed in the absence of IkappaB degradation. To evaluate the role of iron, A549 cells were exposed to PM(10) previously treated with phosphate-buffered saline (PBS), deferoxamine mesylate, or deferoxamine plus ferrozine. PBS-treated and, to a lesser extent, deferoxamine-treated PM(10) were able to activate NF-kappaB, whereas this response was completely abrogated in cells exposed to PM(10) treated with both deferoxamine and ferrozine. Moreover, we studied the effects of soluble components of PM(10) on NF-kappaB activation by exposing alveolar epithelial cells to soluble fractions from PM(10) treated with PBS or the metal chelators. We found that, compared with fractions from PBS-treated PM(10) which activated NF-kappaB, fractions from PM(10) treated with deferoxamine and ferrozine did not stimulate NF-kappaB activity above background levels. Coincubation of polymixin B, an endotoxin-binding compound, and PM(10) did not inhibit NF-kappaB. In summary, PM(10) activates NF-kappaB in A549 cells by an iron-mediated mechanism in the absence of IkappaB degradation.

Adenocarcinoma↗

PubMed2000

Asthma and PM10.

PM10 (the mass of particles present in the air having a 50% cutoff for particles with an aerodynamic diameter of 10 microm) is the standard measure of particulate air pollution used worldwide. Epidemiological studies suggest that asthma symptoms can be worsened by increases in the levels of PM10. Epidemiological evidence at present indicates that PM10 increases do not raise the chances of initial sensitisation and induction of disease, although further research is warranted. PM10 is a complex mixture of particle types and has many components and there is no general agreement regarding which component(s) could lead to exacerbations of asthma. However pro-inflammatory effects of transition metals, hydrocarbons, ultrafine particles and endotoxin, all present to varying degrees in PM10, could be important. An understanding of the role of the different components of PM10 in exacerbating asthma is essential before proper risk assessment can be undertaken leading to advice on risk management for the many asthmatics who are exposed to air pollution particles.

Air Pollution↗

PubMed2000

Effects of the aromatase inhibitor anastrozole on serum oestrogens in Japanese and Caucasian women.

PURPOSE: Substantial differences in plasma oestrogen disposition have been reported between Japanese and Caucasian women, but there are currently few data available on the relative endocrinological effects of aromatase inhibitors in these two groups. Hence, the effects of the nonsteroidal aromatase inhibitor anastrozole on serum oestrogen concentrations were compared in 24 healthy postmenopausal Japanese women and 24 healthy postmenopausal Caucasian women. METHODS: Anastrozole, 1 mg/day, was given once daily for 16 days. Serum oestradiol and oestrone sulphate levels were measured on three consecutive days beginning 2 days before the first dose, and on a further three consecutive days beginning on the penultimate day of dosing. Trough concentrations of anastrozole (measured 24 h after dosing) were also determined during the same periods. RESULTS: There were no substantial differences in plasma oestrogen concentrations between the Japanese and Caucasian women at baseline. On average, anastrozole suppressed serum oestradiol and oestrone sulphate levels by approximately 87% and 93%, respectively, for both Japanese and Caucasian women, and minimum plasma anastrozole concentrations at steady-state (anastrozole C(min)) were also similar in both groups. Statistical analysis of serum oestradiol and serum oestrone sulphate levels, and plasma anastrozole C(min) showed that there were no statistically significant differences between the Japanese and Caucasian women. CONCLUSION: Neither the pharmacodynamic effects of anastrozole on serum oestrogens nor the pharmacokinetics of anastrozole differ between postmenopausal Japanese and Caucasian women. Hence, these findings suggest that the therapeutic benefits of anastrozole in Caucasians will be predictive of the drug's effect in Japanese women and support the use of anastrozole in postmenopausal Japanese women with breast cancer.

Aged↗

PubMed2000

Release of TNFalpha in response to SiC fibres: differential effects in rodent and human primary macrophages, and in macrophage-like cell lines.

Asbestos has been implicated in the pathogenesis of several lung diseases, but its mechanism of action is not fully understood. However, asbestos-induced oxidative stress and production of inflammatory cytokines may play a significant role. TNFalpha is an inflammatory cytokine which has a central role in inflammation and fibrosis due to its ability to stimulate fibroblasts and collagen deposition. In this study, a panel of fibres designated either pathogenic or non-pathogenic in recent animal studies, were utilized. The amount of TNFalpha released after a 16-hour exposure to the panel of fibres was compared in four different cell types; two primary macrophage cell types and two cell lines. TNFalpha release by cells exposed to the panel did not equate to pathogenicity, although the most pathogenic fibre caused three out of the four cell types tested, to produce the greatest amount of TNFalpha. Primary rat cells and primary human cells behaved in a similar manner as regards to TNFalpha production; the cell lines behaved quite differently to their primary counterparts with regards to TNFalpha production in this study.

Animals↗

PubMed2000

Increased calcium influx in a monocytic cell line on exposure to ultrafine carbon black.

Ultrafine particles have been shown to induce pro-inflammatory effects both in vivo and in vitro. Increased expression of pro-inflammatory genes probably requires the activation of specific transcription factors such as nuclear factor kappa B (NF-kappaB) via a number of possible pathways including Ca2+ and reactive oxygen species. The fluorescent dye fura 2, was used to measure cytosolic Ca2+ in the human monocytic cell line, Monomac 6 on exposure to 66 microg x mL(-1) of either ultrafine carbon black (ufCB; diameter 14 nm), carbon black (CB; diameter 260 nm), quartz (diameter 1.45 microm), or medium alone. UfCB but not fine CB induced a 1.6-fold increase (p<0.01) in the resting cytosolic Ca2+ concentration of Monomac 6 cells. In addition ufCB induced a 2.6-fold increase (p<0.001) in the response to the endoplasmic reticulum Ca2+- adenosine triphosphatase (ATPase) inhibitor, thapsigargin, suggesting the Ca2+ release-activated Ca2+ current across the plasma membrane was enhanced. This response was inhibited by the removal of extracellular Ca2+ and by the Ca2+ channel blocker, verapamil. In addition, ufCB stimulated the entry of extracellular Mn2+. Finally, the antioxidants mannitol and nacystelin both inhibited the effects of ufCB on the response to thapsigargin. These data suggest that ultrafine carbon black particles stimulated an increase in cytosolic Ca2+, possibly through the entry of extracellular Ca2+ via Ca2+ channels in the plasma membrane. The particles may in part activate the opening of Ca2+ channels via a mechanism involving reactive oxygen species.

Calcium↗

PubMed2000

Inhalation of poorly soluble particles. I. Differences in inflammatory response and clearance during exposure.

Results from animal studies have indicated some uncertainties over the validity of a single general occupational control limit for all types of "particulates (insoluble) not otherwise classified" (PNOC) (ACGIH, 2000). Therefore, to examine the extent to which a given control limit may be valid for nontoxic dusts with different physical characteristics, this study compared the pulmonary effects in rats of inhalation exposure to two poorly soluble dusts of similar density and with relatively low toxicity: titanium dioxide and barium sulfate. The objectives were to compare the dusts in (a) their buildup and clearance in the lungs during inhalation; (b) their transfer to lymph nodes; (c) the changes, with time, in the lavageable cell population; and (d) the pathological change from histology. The exposure aerosol concentrations were selected to achieve similar mass and volume lung burdens for both dusts and to attain "overload" over the common exposure periods of about 4 mo and 7 mo. Despite obtaining similar lung burdens for both dusts, there was significantly more translocation of TiO(2) to the hilar lymph nodes than with BaSO(4). It was also found that clearance of TiO(2) was retarded whereas clearance of BaSO(4) was not. Trends in these data were clarified by the use of a simple model of particle clearance. Retardation of particle clearance and translocation to the lymph nodes are markers of the condition known as "overload" in which the alveolar macrophage-based clearance of particles from the deep lung is impaired. In addition, bronchoalveolar lavage showed that TiO(2) caused significantly more recruitment of inflammatory neutrophils to lungs than BaSO(4). These differences between the dusts were not due to differences in toxicity, solubility, or lung deposition. The explanation that the different responses are due to the different particle size distributions of the two dust types is examined in a companion paper (Tran et al., this issue).

Administration, Inhalation↗

PubMed2000

Inhalation of poorly soluble particles. II. Influence Of particle surface area on inflammation and clearance.

In this article the volumetric overload hypothesis, which predicts the impairment of clearance of particles deposited in the lung in terms of particle volume, is reevaluated. The degree to which simple expressions of retained lung burden explain pulmonary responses to overload was investigated using data from a series of chronic inhalation experiments on rats with two poorly soluble dusts, titanium dioxide and barium sulfate. The results indicated that the difference between the dusts in the level of inflammation and translocation to the lymph nodes could be explained most simply when the lung burden was expressed as total particle surface area. The shape of the statistical relationship for both lung responses indicated the presence of a threshold at approximately 200-300 cm(2) of lung burden. On the basis of this and other similar results, a hypothesis regarding a generic mechanism for the impairment of clearance and associated lung responses is proposed for such "low-toxicity" dusts.

Administration, Inhalation↗

PubMed2000

Increased inflammation and intracellular calcium caused by ultrafine carbon black is independent of transition metals or other soluble components.

OBJECTIVES: Particulate air pollution has been shown to cause adverse health effects, and the ultrafine particle component has been implicated. The aim of the present study was to investigate whether an ultrafine particle exerted its effects through transition metals or other soluble factors released from the surface of the particles. METHODS: Both in vitro and in vivo models were used to test the imflammogenicity of carbon black (CB) and ultrafine carbon black (UfCB) and the role of transition metals was investigated by treating the particles with desferrioxamine mesylate (desferal), a transition metal chelator. Rats were instilled with particles and the cell population assessed by bronchoalveolar lavage (BAL). Calcium homeostasis in macrophages was assessed with a fluorimetric technique. RESULTS: UfCB was inflammogenic compared with CB when instilled into Wistar rat lungs, an effect which could not be ameliorated by desferal treatment of the particles. Particle leachates produced no significant inflammation in vivo. In vitro experiments showed that the cytosolic calcium ion concentration in Mono Mac 6 cells was increased significantly after UfCB treatment and treatment of particles with desferal did not alter these effects. Particle leachates had no effect on cytosolic calcium ion concentration. Iron was not detected in leachates of the particles with the desferal assay, however, ng/mg of particles were detectable in citrate leachates with inductively coupled plasma-mass spectrometry (ICP-MS). CONCLUSIONS: The increased inflammogenicity of UfCB compared with CB cannot be explained by soluble transition metals released from or by accumulation of iron at the particle surface. Differences may be accounted for by increased surface area or particle number.

Air Pollutants↗

PubMed2000

In vitro toxicology of respirable Montserrat volcanic ash.

OBJECTIVES: In July 1995 the Soufriere Hills volcano on the island of Montserrat began to erupt. Preliminary reports showed that the ash contained a substantial respirable component and a large percentage of the toxic silica polymorph, cristobalite. In this study the cytotoxicity of three respirable Montserrat volcanic ash (MVA) samples was investigated: M1 from a single explosive event, M2 accumulated ash predominantly derived from pyroclastic flows, and M3 from a single pyroclastic flow. These were compared with the relatively inert dust TiO(2) and the known toxic quartz dust, DQ12. METHODS: Surface area of the particles was measured with the Brunauer, Emmet, and Teller (BET) adsorption method and cristobalite content of MVA was determined by x ray diffraction (XRD). After exposure to particles, the metabolic competence of the epithelial cell line A549 was assessed to determine cytotoxic effects. The ability of the particles to induce sheep blood erythrocyte haemolysis was used to assess surface reactivity. RESULTS: Treatment with either MVA, quartz, or titanium dioxide decreased A549 epithelial cell metabolic competence as measured by ability to reduce 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). On addition of mannitol, the cytotoxic effect was significantly less with M1, quartz, and TiO(2). All MVA samples induced a dose dependent increase in haemolysis, which, although less than the haemolysis induced by quartz, was significantly greater than that induced by TiO(2). Addition of mannitol and superoxide dismutase (SOD) significantly reduced the haemolytic activity only of M1, but not M2 or M3, the samples derived from predominantly pyroclastic flow events. CONCLUSIONS: Neither the cristobalite content nor the surface area of the MVA samples correlated with observed in vitro reactivity. A role for reactive oxygen species could only be shown in the cytotoxicity of M1, which was the only sample derived from a purely explosive event. These results suggest that in general the bioreactivity of MVA samples in vitro is low compared with pure quartz, but that the bioreactivity and mechanisms of biological interaction may vary according to the ash source.

Adsorption↗

PubMed2000

Regulation of lipopolysaccharide-mediated interleukin-1beta release by N-acetylcysteine in THP-1 cells.

Increased levels of inflammatory cytokines such as interleukin (IL)-1 and IL-8 occur in the bronchoalveolar lavage fluid in various lung diseases. Cytokine gene expression is controlled by transcription factors such as nuclear factor-kappaB (NF-kappaB) which can be activated by a number of stimuli including the oxidants prevent. It was hypothesized that lipopolysaccharide (LPS)-induced IL-1beta secretion may be modulated by the intracellular thiol redox status of the cells. The effect of the antioxidant compound, N-acetyl-L-cysteine (NAC), on IL-1beta release and regulation of NF-kappaB in a human myelo-monocytic cell line (THP-1) differentiated into macrophages was studied. LPS (10 microg x mL(-1)) increased IL-1beta release at 24 h compared to control levels (p<0.001). NAC (5 mM) also enhanced LPS-induced IL-1beta release from THP-1 cells (p<0.001). In addition, treatment of cells with cycloheximide, an inhibitor of protein synthesis, inhibited the NAC-mediated IL-1beta release. Under the same conditions, NF-kappaB binding was activated by LPS and NAC increased this LPS-mediated effect. Western blot analysis revealed that NAC treatment leads to an increase in p50 and p65 protein synthesis. These data indicate that N-acetyl-L-cysteine modulates interleukin-1kappa release by increasing levels of the homo- and heterodimeric forms of nuclear factor-kappaB.

Acetylcysteine↗

PubMed2000

Exacerbations of COPD: environmental mechanisms.

Air pollution as a trigger for exacerbations of COPD has been recognized for > 50 years, and has led to the development of air quality standards in many countries that substantially decreased the levels of air pollutants derived from the burning of fossil fuels, such as black smoke and sulfur dioxide. However, the recent dramatic increase in motor vehicle traffic has produced a relative increase in the levels of newer pollutants, such as ozone and fine-particulate air pollution < 10 microm in diameter. Numerous epidemiologic studies have shown associations between the levels of these air pollutants and adverse health effects, such as exacerbations of airways diseases and even deaths from respiratory and cardiovascular causes. Elucidation of the mechanism of the harmful effects of these pollutants should allow improved risk assessment for patients with airways diseases who are be susceptible to the effects of these air pollutants.

Air Pollutants↗

PubMed2000

Depletion of glutathione and ascorbate in lung lining fluid by respirable fibres.

OBJECTIVE: The use of synthetic vitreous fibres has increased along with a decline in the utilisation of asbestos. There remains concern that these synthetic fibres pose a health risk to workers because of the generation of respirable fibres which can enter the lung and cause adverse health effects. An improved understanding of the mechanism of fibre pathogenicity should allow more rational short-term testing regimes for new fibres as they are developed. We hypothesised that carcinogenic fibres have greater free radical activity compared with non-carcinogenic fibres and that they contribute to disease by causing oxidative stress in the lung. We examined a panel of respirable fibres, designated as being carcinogenic or non-carcinogenic based on previous animal studies for ability to deplete antioxidants from lung lining fluid. METHODS: On the basis of inhalation studies, a panel of fibres was divided into three carcinogenic fibres-amosite asbestos, silicon carbide, and refractory ceramic fibre 1 (RCF1) and three non-carcinogenic fibres-man-made vitreous fibre 10 (a glass fibre MMVF10), Code 100/475 glass fibre, and refractory ceramic fibre 4 (RCF4). We measured the levels of glutathione (GSH) and ascorbate, two antioxidants present in lung lining fluid (LLF) after fibre treatment. All of the experiments were carried out at equal fibre number. RESULTS: Fibres had the ability to deplete both GSH and ascorbate from both LLF and pure solutions, an effect which was fibre number dependent. The greatest depletion of antioxidants was observed with the two non-carcinogenic glass fibres, and this effect was observed when A549 lung epithelial cells were treated with fibres. CONCLUSIONS: Our results show that antioxidant depletion in cell free solution and lung lining fluid solely is not a simple indicator of the ability of fibres to cause lung pathology and that other biological events in the lung are involved.

Analysis of Variance↗