Clara Cell protein and myeloperoxidase levels in serum of subjects after exposure to fire smoke

Introduction. Fire smoke inhalation is a well-recognized aetiological factor of airway injuries. The objective of this study was evaluation of Clara cell protein (CC16) and myeloperoxidase (MPO) concentrations in serum of patients after exposure to uncontrolled fire smoke. Methods. The study group consisted of 40 consecutive patients admitted to the Toxicology Unit after exposure to fire smoke. CC16 and MPO concentrations in their serum samples was measured on the day of admission to hospital and rechecked at the 2nd day and on the day of discharge. Patients also underwent routine toxicological diagnostic procedures applied in case of exposures, such as carboxyhaemoglobin (COHb) levels and blood lactate and urinary thiocyanate concentrations. The same diagnostic tests were performed in the control group consisting of 10 healthy subjects not exposed to fire smoke. Results. The average concentration of CC16 in the serum of subjects exposed to toxic factors was significantly higher at the day of admission in comparison with the respective values recorded on the 2nd day and on the day of discharge. The mean level of CC16 in the serum of the exposed group was also significantly higher than that in the control group. Tests for MPO concentrations in the serum did not reveal any significant changes in patients exposed to fire smoke. Conclusions. As indicated, acute exposure to smoke induces injury at the alveolar level, which results in a transient increase of CC16 in serum of exposed subjects.Wstęp. Narażenie na dymy pożarowe jest udokumentowaną przyczyną toksycznego uszkodzenia układu oddechowego. Celem badania była ocena stężeń bialka Clara i mieloperoksydazy w surowicy osób narażonych na dymy pożarowe.Metody. Grupę badaną stanowiło 40 osób narażonych na dymy pożarowe, które zostały przyjęte na oddział toksykologii. Stężenia białka Clara i mieloperoksydazy oznaczono w dniu przyjęcia do szpitala oraz ponownie w drugim i ostatnim dniu hospitalizacji. U pacjentów wykonano także badania toksykologiczne zlecane przy tego typu narażeniu: stężenie karboksyhemoglobiny i stężenie mleczanów we krwi oraz stężenie rodanków w moczu. Podobny panel badań zlecono u 10 zdrowych osób (grupa kontrolna) nienarażonych na dymy pożarowe. Wyniki. Stężenie białka Clara było istotnie statystycznie wyższe w surowicy pacjentów narażonych na dymy pożarowe w dniu ich przyjęcia do szpitala w porównaniu z wartością tego parametru ocenianego w drugim i ostatnim dniu hospitalizacji. Stężenie białka Clara było również istotnie wyższe w surowicy osób narażonych w porównaniu z grupą kontrolną. Nie obserwowano istotnych zmian steżenia MPO w surowicy osób eksponowanych na dymy pożarowe. Wnioski. Narażenie na dymy pożarowe może prowadzić do uszkodzenia pęcherzyków płucnych, a tym samym do wzrostu w surowicy osób narażonych stężenia białka Clara uwalnianego przez te komórki

Toxic effect in the lungs of rats after inhalation exposure to benzalkonium chloride

Background: Benzalkonium chloride (BAC) is a quaternary ammonium compound (QAC) toxic to microorganisms. Inhalation is one of the major possible routes of human exposure to BAC. Materials and Methods: Experiments were performed on female Wistar rats. The rats were exposed to aerosol of BAC water solution at the target concentration of 0 (control group) and 35 mg/m3 for 5 days (6 h/day) and, after a 2-week interval, the animals were challenged (day 21) with BAC aerosol at the target concentration of 0 (control group) and 35 mg/m3 for 6 h. Results: Compared to the controls, the animals exposed to BAC aerosol were characterized by lower food intake and their body weight was significantly smaller. As regards BAC-exposed group, a significant increase was noted in relative lung mass, total protein concentration, and MIP-2 in BALF both directly after the termination of the exposure and 18 h afterwards. Significantly higher IL-6 and IgE concentrations in BALF and a decrease in the CC16 concentration in BALF were found in the exposed group immediately after the exposure. The leukocyte count in BALF was significantly higher in the animals exposed to BAC aerosol compared to the controls. In the lungs of rats exposed to BAC the following effects were observed: minimal perivascular, interstitial edema, focal aggregates of alveolar macrophages, interstitial mononuclear cell infiltrations, thickened alveolar septa and marginal lipoproteinosis. Conclusion: Inhalation of BAC induced a strong inflammatory response and a damage to the blood-air barrier. Reduced concentrations of CC16, which is an immunosuppressive and anti-inflammatory protein, in combination with increased IgE concentrations in BALF may be indicative of the immuno-inflammatory response in the animals exposed to BAC aerosol by inhalation. Histopathological examinations of tissue samples from the BAC-exposed rats revealed a number of pathological changes found only in the lungs

NEUROLOGICAL AND RESPIRATORY SYMPTOMS IN SHIPYARD WELDERS EXPOSED TO MANGANESE O R I G I N A L P A P E R S IJOMEH 2005;18(3) 266

Abstract Objective: The nervous system is the major target of the toxic effect of manganese (Mn) and its compounds in welding fumes. In humans, inhalation is the most frequent route of Mn access, therefore, the respiratory tract and lungs are usually involved in the process of translocation of inhaled noxius agent by blood to the brain. This study was performed to assess whether it is possible to use neurophysiological tests for the detection of early effects of exposure to low Mn concentrations. It is also known that irritating welding fumes affect distal bronchioles of nonciliated, epithelial Clara cells, which secret antiinflammatory and immunossupresive Clara cell protein (CC16) into the respiratory tract. The examination of usefulness of CC16 as early pulmonary biomarker for neurophysiological abnormal results of welding fumes exposure was performed. Materials and Methods: The study group comprised 59 welders employed at different workposts in a shipyard, matched for age and smoking habits with the control group composed of 23 mechanicians and electricians not exposed to welding fumes. Subjective neurological symptops (CNS), visual evoked potentials (VEP) and electroencephalography (EEG) were examined in welders and the relationships between Mn concentrations in the air, blood and urine as well as between cummulative exposure index (CEI) (Mn mg/m 3 • years of exposure) were investigated. Effects of exposure were expressed in the form of biomarkers of the body burden, and CC16 as early pulmonary biomarker in welding exposure was examined by sensitive latex-immunoassay. Results: Abnormal results of VEP and EEG and the lowest CC16 levels were found in the youngest welders exposed to welding fumes. Those changes were related to the highest Mn airborne levels (x g > 0.3 mg/m 3 ) and high blood Mn concentrations (~14.0 mg/dL). The highest values of correlation coefficients were found only in welders characterized by abnormal neurophysiological results, VEP (r = 0.83) and VEP and VEP+EEG (r = 0.82). The multiple linear regression analysis from all analyzed subgroups, indicated that those with only abnormal neurophysiological tests, VEP and EEG, showed the highest values of partial correlation. It also revealed partial correlation cofficiants between Mn in the air, CEI (Mn mg/m 3 • years) and CC16, Mn-B and Mn-U in VEP and VEP+EEG groups. It was found that the highest partial correlations were between the magnitude of exposure -Mn mg/m 3 , CEI and Mn-B concentration (R 2 = 0.72, R 2 = 0.66) as well as between CC16 pulmonary biomarker effects and Mn-B concentration (R 2 = 0.51). Conclusions: The subclinical effects revealed in neurological endpoints and abnormal results of neurophysiological tests, VEP and EEG, confirmed that those sensitive tests could be used for the detection of early effect of exposure to low manganese concentration. Inhibition of Clara cell protein secretion in younger welders not adapted to the Mn environment suppresses anti-inflammatory effect in the respiratory tract and probably enhances the absorption and thus the incidence of subclinical neurotoxic symptoms related to airborne Mn and Mn-B levels

Clara cells protein, prolactin and transcription factors of protein NF-ĸB and c-Jun/AP-1 levels in rats inhaled to stainless steel welding dust and its soluble form

Objectives Welding processes that generate fumes containing toxic metals, such as hexavalent chromium (Cr(VI)), manganese, and nickel (Ni), have been implicated in lung injury, inflammation, and lung tumor promotion in animal models. Bronchiolar epithelium Clara cells/club cells, coordinate these inflammatory responses. Clara cells secretory protein (CC16) with ant-inflammatory role. Material and Methods The pulmonary toxicity of welding dust (WD) was assessed for Wistar rats exposed to 60 mg/m 3 of respirable-size welding dust (mean diameter 1.17 μm for 1 and 2 weeks (6 h/day, 5 days/week)) or the aerosols of soluble form (SWD) in the nose-only exposure chambers. Additionally the effect of antiinflammatory betaine supplementation was assessed. Clara cells secretory protein, differential cell counts, total protein concentrations and cellular enzyme (lactate dehydrogenase – LDH) activities were determined in bronchoalveolar lavage fluid, and corticosterone and thiobarbituric acid reactive substances (TBARS) and prolactin concentrations were assessed in serum. Histopathology examination of lung, brain, liver, kidney, spleen was done. Additionally slices of brain and lung were exanimated in laser ablation inductively coupled plasma mass spectrometry. Results Both WD and SWD exposure evoked large bronchiolar infiltration shoved in histopathology examination. In this study, TBARS inversely correlated with a significant decrease of CC16 concentration that occurred after instillation of both WD and SWD indicating decreased anti- inflammatory potential in the lung. In WD exposed rats prolactin correlated with nuclear factor-kappa B (NF-κB), LDH, TBARS and serum levels Cr, Ni and inversely with c-Jun. In SWD exposed rats prolactin correlated with CC16 indicated effect of prolactin on the population of epithelial cells. Conclusions In the current study, deleterious effects of repeated inhalation stainless steel welding dust form on club (Clara) cell secretory protein (CC16) were demonstrated. Clara cells secretory protein relation with prolactin in exposed rats to welding dust were shown and explored whether the NF-κB and c-Jun/activator protein 1 related pathway was involved. Int J Occup Med Environ Health 2018;31(5):613–63

Toxic effect in the lungs of rats after inhalation exposure to benzalkonium chloride

Background: Benzalkonium chloride (BAC) is a quaternary ammonium compound (QAC) toxic to microorganisms. Inhalation is one of the major possible routes of human exposure to BAC. Materials and Methods: Experiments were performed on female Wistar rats. The rats were exposed to aerosol of BAC water solution at the target concentration of 0 (control group) and 35 mg/m3 for 5 days (6 h/day) and, after a 2-week interval, the animals were challenged (day 21) with BAC aerosol at the target concentration of 0 (control group) and 35 mg/m3 for 6 h. Results: Compared to the controls, the animals exposed to BAC aerosol were characterized by lower food intake and their body weight was significantly smaller. As regards BAC-exposed group, a significant increase was noted in relative lung mass, total protein concentration, and MIP-2 in BALF both directly after the termination of the exposure and 18 h afterwards. Significantly higher IL-6 and IgE concentrations in BALF and a decrease in the CC16 concentration in BALF were found in the exposed group immediately after the exposure. The leukocyte count in BALF was significantly higher in the animals exposed to BAC aerosol compared to the controls. In the lungs of rats exposed to BAC the following effects were observed: minimal perivascular, interstitial edema, focal aggregates of alveolar macrophages, interstitial mononuclear cell infiltrations, thickened alveolar septa and marginal lipoproteinosis. Conclusion: Inhalation of BAC induced a strong inflammatory response and a damage to the blood-air barrier. Reduced concentrations of CC16, which is an immunosuppressive and anti-inflammatory protein, in combination with increased IgE concentrations in BALF may be indicative of the immuno-inflammatory response in the animals exposed to BAC aerosol by inhalation. Histopathological examinations of tissue samples from the BAC-exposed rats revealed a number of pathological changes found only in the lungs

Neurological and neurophysiological examinations of workers exposed to arsenic levels exceeding hygiene standards

Objectives: The assessment of the neurotoxic effect of arsenic (As) and its inorganic compounds is still the subject of interest due to a growing As application in a large array of technologies and the need to constantly verify the principles of prevention and technological parameters. The aim of this study was to determine the status of the nervous system (NS) in workers exposed to As at concentrations exceeding hygiene standards (Threshold Limit Values (TLV) – 10 μg/m3, Biological Exposure Index (BEI) – 35 μg/l) and to analyze the relationship between the NS functional state, species of As in urine and As levels in the workplace air. Material and Methods: The study group comprised 21 men (mean age: 47.43±7.59) employed in a copper smelting factory (mean duration of employment: 22.29±11.09). The control group comprised 16 men, matched by age and work shifts. Arsenic levels in the workplace air (As-A) ranged from 0.7 to 92.3 μg/m3; (M = 25.18±28.83). The concentration of total arsenic in urine (Astot-U) ranged from 17.35 to 434.68 μg/l (M = 86.82±86.6). Results: Syndrome of peripheral nervous system (PNS) was manifested by extremity fatigue (28.6%), extremity pain (33.3%) and paresthesia in the lower extremities (33.3%), as well as by neuropathy-type mini-symptoms (23.8%). Electroneurographic (ENeG) tests of peroneal nerves showed significantly decreased response amplitude with normal values of motor conduction velocity (MCV). Stimulation of sural nerves revealed a significantly slowed sensory conduction velocity (SCV) and decreased sensory potential amplitude. Neurophysiological parameters and the results of biological and environmental monitoring showed a relationship between Astot, AsIII (trivalent arsenic), the sum of iAs (AsIII+AsV (pentavalent arsenic))+MMA (monomethylarsonic acid) concentration in urine and As levels in the air. Conclusions: The results of the study demonstrate that occupational exposure to inorganic arsenic levels exceeding hygiene standards (TLV, BEI) generates disorders typical of peripheral neuropathy