The inhalation of metal (including lead) nanoparticles poses a real health issue to people and animals living in polluted and/or industrial areas. In this study, we exposed mice to lead(II) nitrate nanoparticles [Pb(NO3)2 NPs], which represent a highly soluble form of lead, by inhalation. We aimed to uncover the effects of their exposure on individual target organs and to reveal potential variability in the lead clearance. We examined (i) lead biodistribution in target organs using laser ablation and inductively coupled plasma mass spectrometry (LA-ICP-MS) and atomic absorption spectrometry (AAS), (ii) lead effect on histopathological changes and immune cells response in secondary target organs and (iii) the clearance ability of target organs. In the lungs and liver, Pb(NO3)2 NP inhalation induced serious structural changes and their damage was present even after a 5-week clearance period despite the lead having been almost completely eliminated from the tissues. The numbers of macrophages significantly decreased after 11-week Pb(NO3)2 NP inhalation; conversely, abundance of alpha-smooth muscle actin (α-SMA)-positive cells, which are responsible for augmented collagen production, increased in both tissues. Moreover, the expression of nuclear factor κB (NF-κB) and selected cytokines, such as tumor necrosis factor alpha (TNFα), transforming growth factor beta 1 (TGFβ1), interleukin 6(IL-6), IL-1α and IL-1β , displayed a tissue-specific response to lead exposure. In summary, diminished inflammatory response in tissues after Pb(NO3)2 NPs inhalation was associated with prolonged negative effect of lead on tissues, as demonstrated by sustained pathological changes in target organs, even after long clearance period.

• Klíčová slova
• LA-ICP-MS imaging, clearance, inhalation, lead nanoparticles, toxicity,
• MeSH
• aktiny agonisté   genetika   imunologie   MeSH
• alveolární makrofágy účinky léků   imunologie   patologie   MeSH
• aplikace inhalační MeSH
• biologická dostupnost MeSH
• dusičnany farmakokinetika   toxicita   MeSH
• exprese genu MeSH
• inhalační expozice analýza   MeSH
• interleukin-1alfa agonisté   genetika   imunologie   MeSH
• interleukin-1beta agonisté   genetika   imunologie   MeSH
• interleukin-6 agonisté   genetika   imunologie   MeSH
• játra účinky léků   imunologie   patologie   MeSH
• kovové nanočástice aplikace a dávkování   toxicita   MeSH
• látky znečišťující vzduch farmakokinetika   toxicita   MeSH
• myši inbrední ICR MeSH
• myši MeSH
• NF-kappa B agonisté   genetika   imunologie   MeSH
• olovo farmakokinetika   toxicita   MeSH
• plíce účinky léků   imunologie   patologie   MeSH
• poločas MeSH
• spektrofotometrie atomová MeSH
• tkáňová distribuce MeSH
• TNF-alfa agonisté   genetika   imunologie   MeSH
• transformující růstový faktor beta1 agonisté   genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aktiny MeSH
• alpha-smooth muscle actin, mouse MeSH Prohlížeč
• dusičnany MeSH
• Il1a protein, mouse MeSH Prohlížeč
• IL1B protein, mouse MeSH Prohlížeč
• interleukin-1alfa MeSH
• interleukin-1beta MeSH
• interleukin-6, mouse MeSH Prohlížeč
• interleukin-6 MeSH
• látky znečišťující vzduch MeSH
• lead nitrate MeSH Prohlížeč
• NF-kappa B MeSH
• olovo MeSH
• Tgfb1 protein, mouse MeSH Prohlížeč
• TNF-alfa MeSH
• transformující růstový faktor beta1 MeSH

Throughout the development of breath analysis research, there has been interest in how the concentrations of trace compounds in exhaled breath are related to their concentrations in the ambient inhaled air. In considering this, Phillips introduced the concept of 'alveolar gradient' and judged that the measured exhaled concentrations of volatile organic compounds should be diminished by an amount equal to their concentrations in the inhaled ambient air. The objective of the work described in this paper was to investigate this relationship quantitatively. Thus, experiments have been carried out in which inhaled air was polluted by seven compounds of interest in breath research, as given below, and exhaled breath has been analysed by SIFT-MS as the concentrations of these compounds in the inhaled air were reduced. The interesting result obtained is that all the exogenous compounds are partially retained in the exhaled breath and there are close linear relationships between the exhaled and inhaled air concentrations for all seven compounds. Thus, retention coefficients, a, have been derived for the following compounds: pentane, 0.76 ± 0.09; isoprene, 0.66 ± 0.04; acetone, 0.17 ± 0.03; ammonia, 0.70 ± 0.13, methanol, 0.29 ± 0.02; formaldehyde, 0.06 ± 0.03; deuterated water (HDO), 0.09 ± 0.02. From these data, correction to breath analyses for inhaled concentration can be described by coefficients specific to each compound, which can be close to 1 for hydrocarbons, as applied by Phillips, or around 0.1, meaning that inhaled concentrations of such compounds can essentially be neglected. A further deduction from the experimental data is that under conditions of the inhalation of clean air, the measured exhaled breath concentrations of those compounds should be increased by a factor of 1/(1 - a) to correspond to gaseous equilibrium with the compounds dissolved in the mixed venous blood entering the alveoli. Thus, for isoprene, this is a factor of 3, which we have confirmed experimentally by re-breathing experiments.

• MeSH
• aceton farmakokinetika   MeSH
• amoniak farmakokinetika   MeSH
• butadieny farmakokinetika   MeSH
• dechové testy * MeSH
• formaldehyd farmakokinetika   MeSH
• hemiterpeny farmakokinetika   MeSH
• hmotnostní spektrometrie metody   MeSH
• látky znečišťující vzduch farmakokinetika   MeSH
• lidé MeSH
• methanol farmakokinetika   MeSH
• nadechnutí * MeSH
• oxid deuteria farmakokinetika   MeSH
• pentany farmakokinetika   MeSH
• vydechnutí * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aceton MeSH
• amoniak MeSH
• butadieny MeSH
• formaldehyd MeSH
• hemiterpeny MeSH
• isoprene MeSH Prohlížeč
• látky znečišťující vzduch MeSH
• methanol MeSH
• oxid deuteria MeSH
• pentany MeSH

OBJECTIVES: 2-Nitrobenzanthrone (2-NBA) has recently been detected in ambient air particulate matter. Its isomer 3-nitrobenzanthrone (3-NBA) is a potent mutagen and suspected human carcinogen identified in diesel exhaust. Understanding which enzymes are involved in metabolism of these toxicants is important in the assessment of individual susceptibility. Here, metabolism of 2-NBA and 3-NBA by rat and mouse hepatic microsomes containing cytochromes P450 (CYPs), their reductase (NADPH:CYP reductase), and NADH:cytochrome b5 reductase was investigated under anaerobic and aerobic conditions. In addition, using the same microsomal systems, 2-NBA and 3-NBA were evaluated to be enzymatically activated under anaerobic conditions to species generating 2-NBA- and 3-NBA-derived DNA adducts. METHODS: High performance liquid chromatography (HPLC) with ultraviolet (UV) detection was employed for the separation and characterization of 2-NBA and 3-NBA metabolites formed by hepatic microsomes of rats and mice under the anaerobic and aerobic conditions. Microsomal systems isolated from the liver of the control (untreated) rats and rats pretreated with Sudan I, β-naphthoflavone (β-NF), phenobarbital (PB), ethanol and pregnenolon 16α-carbonitrile (PCN), the inducers of cytochromes P450 (CYP) 1A1, 1A1/2, 2B, 2E1 and 3A, respectively, were used in this study. Microsomes of mouse models, a control mouse line (wild-type, WT) and Hepatic Cytochrome P450 Reductase Null (HRN) mice with deleted gene of NADPH:CYP reductase in the liver, thus absenting this enzyme in their livers, were also employed. To detect and quantify the 2-NBA- and 3-NBA-derived DNA adducts, the 32P postlabeling technique was used. RESULTS: Both reductive metabolite of 3-NBA, 3-aminobenzanthrone (3-ABA), found to be formed predominantly under the anaerobic conditions, and two 3-NBA oxidative metabolites, whose structures have not yet been investigated, were formed by several microsomal systems used in the study. Whereas a 3-NBA reductive metabolite, 3-ABA, was found only in the microsomal systems of control rats, the rats treated with β-NF and PB, and microsomes of WT and HRN mice, all hepatic microsomes tested in the study were capable of activating this carcinogen under the reductive conditions to form DNA adducts. A stability of a reactive intermediate of 3-NBA, N-hydroxy-3-aminobenzanthrone that is formed during 3-NBA reduction to 3-ABA, to form nitrenium (and/or carbenium) ions binding to DNA in individual microsomes as well as binding of these ions to proteins of these microsomes, might be the reasons explaining this phenomenon. In contrast to 3-NBA, its isomer 2-NBA was not metabolized by any of the used enzymatic systems both under the anaerobic and aerobic conditions. Likewise, no DNA adducts were detectable after reaction of 2-NBA in these systems with DNA. CONCLUSIONS: The results found in this study, the first report on the metabolism of 2-NBA and 3-NBA by rat and mouse hepatic microsomes demonstrate that 3-NBA, in contrast to 2-NBA, is reductively activated to form 3-NBA-derived DNA adducts by these enzymatic systems. NADPH:CYP reductase can be responsible for formation of these DNA adducts in rat livers, while NADH:cytochrome b5 reductase can contribute to this process in livers of HRN mice.

• MeSH
• adukty DNA metabolismus   MeSH
• aerobióza fyziologie   MeSH
• anaerobióza fyziologie   MeSH
• benz(a)anthraceny farmakokinetika   toxicita   MeSH
• cytochrom-B(5)-reduktasa genetika   metabolismus   MeSH
• inbrední kmeny myší MeSH
• jaterní mikrozomy enzymologie   MeSH
• karcinogeny farmakokinetika   toxicita   MeSH
• krysa rodu Rattus MeSH
• látky znečišťující vzduch farmakokinetika   toxicita   MeSH
• metabolická inaktivace fyziologie   MeSH
• modely u zvířat MeSH
• myši knockoutované MeSH
• myši MeSH
• NADPH-cytochrom c-reduktasa metabolismus   MeSH
• potkani Wistar MeSH
• substrátová specifita fyziologie   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• výfukové emise vozidel toxicita   MeSH
• zdraví ve městech MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 3-nitrobenzanthrone MeSH Prohlížeč
• adukty DNA MeSH
• benz(a)anthraceny MeSH
• cytochrom-B(5)-reduktasa MeSH
• karcinogeny MeSH
• látky znečišťující vzduch MeSH
• N-hydroxy-2-aminobenzanthrone MeSH Prohlížeč
• N-hydroxy-3-aminobenzanthrone MeSH Prohlížeč
• NADPH-cytochrom c-reduktasa MeSH
• Ncb5or protein, mouse MeSH Prohlížeč
• systém (enzymů) cytochromů P-450 MeSH
• výfukové emise vozidel MeSH

3-Nitrobenzanthrone (3-NBA) is an extremely potent mutagen and suspect human carcinogen found in diesel exhaust. Its isomer 2-nitrobenzanthrone (2-NBA) has also been found in ambient air. These isomers differ in mutagenicity in Salmonella by 2-3 orders of magnitude. To identify their urinary metabolites and also to assess the assumed differences in their excretion, rats were dosed orally with 2mg/kg b.w. of either 2-NBA or 3-NBA. Their urine was collected for two consecutive days after dosage. Both LC-ESI-MS and GC-MS confirmed formation of the corresponding aminobenzanthrones (ABA). Excretion of these metabolites within the first day after dosing with 2- and 3-ABA amounted to 0.32±0.06 and 0.83±0.40% of the doses, respectively, while the excretion within the second day was by one order of magnitude lower. A novel mercapturic acid metabolite of 3-NBA was identified in urine by LC-ESI-MS as N-acetyl-S-(3-aminobenzanthron-2-yl)cysteine (3-ABA-MA) by comparison with the authentic standard. Its excretion amounted to 0.49±0.15 and 0.02±0.01% of dose within the first and second day after dosing, respectively. In contrast, no mercapturic acid was detected in the urine of rats dosed with 2-NBA. Observed difference in the mercapturic acid formation between 2- and 3-NBA is a new distinctive feature reflecting differences in the critical step of their metabolism, i.e., benzanthronylnitrenium ion formation that is intrinsically associated with biological activities of these two isomers. Moreover, 3-ABA-MA is a promising candidate biomarker of exposure to the carcinogenic 3-NBA.

• MeSH
• acetylcystein moč   MeSH
• benz(a)anthraceny chemie   farmakokinetika   moč   MeSH
• hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
• karcinogeny chemie   metabolismus   MeSH
• krysa rodu Rattus MeSH
• látky znečišťující vzduch chemie   farmakokinetika   moč   MeSH
• magnetická rezonanční spektroskopie MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 3-nitrobenzanthrone MeSH Prohlížeč
• acetylcystein MeSH
• benz(a)anthraceny MeSH
• karcinogeny MeSH
• látky znečišťující vzduch MeSH

Uptake of organochlorine pesticides and polychlorinated biphenyls from soil and air into radishes was measured at a heavily contaminated field site. The highest contaminant concentrations were found for DDT and its metabolites, and for beta-hexachlorocyclohexane. Bioconcentration factor (BCF, defined as a ratio between the contaminant concentration in the plant tissue and concentration in soil) was determined for roots, edible bulbs and shoots. Root BCF values were constant and not correlated to log K(OW). A negative correlation between BCF and log K(OW) was found for edible bulbs. Shoot BCF values were rather constant and varied between 0.01 and 0.22. Resuspended soil particles may facilitate the transport of chemicals from soil to shoots. Elevated POP concentrations found in shoots of radishes grown in the control plot support the hypothesis that the uptake from air was more significant for shoots than the one from soil. The uptake of POPs from air was within the range of theoretical values predicted from log K(OA).

• MeSH
• chlorované uhlovodíky analýza   farmakokinetika   MeSH
• kořeny rostlin metabolismus   MeSH
• látky znečišťující půdu analýza   farmakokinetika   MeSH
• látky znečišťující vzduch farmakokinetika   MeSH
• monitorování životního prostředí metody   MeSH
• polychlorované bifenyly analýza   farmakokinetika   MeSH
• Raphanus metabolismus   MeSH
• rezidua pesticidů analýza   farmakokinetika   MeSH
• výhonky rostlin metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chlorované uhlovodíky MeSH
• látky znečišťující půdu MeSH
• látky znečišťující vzduch MeSH
• polychlorované bifenyly MeSH
• rezidua pesticidů MeSH

A biomonitoring study using domestic rabbits (Chinchilla) aimed at the exposure and impact risks assessment of emissions released into the ambient air from a mercury-recycling plant has been carried out. Groups of rabbits were exposed to the emissions during 6 months at biomonitoring stations built up in two localities (Rudnany and Matejovce) in the distance of about 3 and 6 km around and downwind from the mercury-producing plant. The aim of the biomonitoring was to trace the translocation of inhaled inorganic Hg in body tissues and the immunotoxic impact of the emissions in the exposed mammalian organism in comparison to a non-exposed animals living outside the polluted area. The content of mercury (as a major pollutant in the ambient air in that area) in body tissues was done spectrometrically using a Trace Mercury Analyser TMA-254. Content of mercury and the other metals in the rabbits' hairs was determined by neutron activation analysis. A statistically significant increase of the inorganic Hg content in the specimens of kidneys, lungs, liver, thigh bone, heart muscle and brain was observed. Concerning the hairs, a statistically significant elevation of Hg and other elements (As, Cd, La, Zn, Na, K, W, Sr) has been found. The body tissue reaction to the increased accumulation of mercury has been investigated by a direct immunofluorescent method to search for body tissue immune complexes. The significant increase of Hg content determined in the organs (especially in kidneys and liver) of the exposed animals was also traced by the presence of immunofluorescent antibodies. In addition, the immunofluorescent antibodies in the myocardium have been proved.(ABSTRACT TRUNCATED AT 250 WORDS)

• MeSH
• králíci MeSH
• látky znečišťující vzduch farmakokinetika   MeSH
• rtuť farmakokinetika   MeSH
• tkáňová distribuce MeSH
• tvorba protilátek MeSH
• vystavení vlivu životního prostředí analýza   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• látky znečišťující vzduch MeSH
• rtuť MeSH

The metabolism and toxicokinetics of cyclohexanone (CH-one), an important solvent and chemical intermediate, have been studied in volunteers during and after 8-h exposures to CH-one vapour at a concentration of 101, 207 and 406 mg.m-3. The pulmonary ventilation in these experiments was typically 11 l.min-1 and retention in the respiratory tract was 58%. After exposure to CH-one, 207 mg.m-3, the metabolic yields of cyclohexanol (CH-ol), 1,2- and 1,4-cyclohexanediol (CH-diol) as determined in urine by a gas chromatographic method involving hydrolysis of glucuronide conjugate were 1.0% +/- 0.3%, 39% +/- 5% and 18% +/- 2% (n = 8), respectively. Peak excretion of CH-ol was achieved at the end of the exposure period, after which it decayed rapidly. Elimination of 1,2- and 1,4-CH-diol reached maximum values a few hours following exposure, with subsequent elimination half-times of 16 +/- 2 and 18 +/- 4 h, respectively. Repeated exposure to CH-one vapour (around 200 mg.m-3) for five consecutive days (8 h/day) resulted in cumulative excretion of CH-diols. The permeation rate of CH-one liquid through the skin was 0.037-0.069 mg.cm-2.h-1 (n = 3), indicating that the contribution of percutaneous absorption to total CH-one occupational intake is of minor importance. CH-diols are recommended as biomarkers of exposure to CH-one.

• MeSH
• aplikace inhalační MeSH
• aplikace kožní MeSH
• biologické markery MeSH
• cyklohexanoly metabolismus   MeSH
• cyklohexanony metabolismus   farmakokinetika   moč   MeSH
• dospělí MeSH
• dýchání fyziologie   MeSH
• kožní absorpce fyziologie   MeSH
• látky znečišťující vzduch metabolismus   farmakokinetika   moč   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monitorování životního prostředí metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• cyklohexanoly MeSH
• cyklohexanony MeSH
• látky znečišťující vzduch MeSH