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Biomedical subjects

K Rydzyński

Publications and source records attributed to K Rydzyński.

At least 19 recordsLinked to original sources

Assessment of usefulness of J774A.1 macrophages for the assay of IL-1beta promoter activity.

Existing data indicate that the increase of il-1beta gene expression can be a promising marker of Langerhans cells activation after exposure to contact sensitizers. In this study, we were interested in development of an alternative in vitro screening test detecting such sensitizers. Two IL-1beta reporter constructs containing the enhanced green fluorescent protein (GFP) gene and mouse IL-1beta promoter fragments of varying lengths (-500 bp and -4093 bp) were used for transient transfections of J771A.1 murine monocyte-macrophage cells. As a result of the transfections performed using Lipofectamine reagent we did not observe any GFP fluorescence after stimulation of the cells with LPS as well as known sensitizers (potassium tetrachloroplatinate, dinitrochlorobenzene and nickel sulfate). Low transfection efficiency of J774A.1 cells (less than 0.1%) was confirmed using control plasmid containing GFP gene under the control of cytomegalovirus promoter. The fact that, using the same conditions, we were able to transfect murine fibroblasts 3T3-L1 with the control plasmid very efficiently, may support the theory of high metabolic activity of macrophages being responsible for the extremely low transfection efficiency. These data suggest limited suitability of J774A.1 cell line for transient transfections using cationic liposomes.

3T3-L1 Cells↗

Serum clara-cell protein and beta2-microglobulin as early markers of occupational exposure to nitric oxides.

Biochemical effects of NOx on 60 workers (both genders) of nitric acid production were studied. The control group consisted of 61 nonexposed people employed elsewhere in the plant. Although the actual threshold limit valuetime weighted averages (TLV-TWA) were not exceeded in the specific conditions of our study, the subjects were exposed to NO2 and NO during several exposure episodes with peak maximal concentrations of 140 ppm and 515 ppm, respectively. Additional cross-week evaluation of several biochemical biomarkers in 15 NOx-exposed workers from one shift was performed. The objective of the study was to evaluate the value of serum Clara-cell protein (CC16) as a marker of bronchoalveolar epithelium activity. Antioxidant status was assessed by measuring activity of enzymes: glutathione peroxidase (GSH-Px), ceruloplasmin (Cp) in plasma, or superoxide dismutase (SOD), gluthatione S-transferase (GST), and nonenzymatic alpha-tocopherol in erythrocytes and thiobarbituric acid-reactive substances (TBARS) in plasma. Serum hyaluronic acid (HA) determining the connective tissue matrix status of airways, and beta2-microglobulin in serum (beta2M-S) and urine (beta2M-U) as a marker of renal function in occupational exposure to NOx were also employed. Exposure to NOx initiates peroxidative chain depleting of lipoprotein pool (alpha-tocopherol) in blood. Serum CC16 levels in NOx-exposed workers were found to be closely connected with alpha-tocopherol content. In NOx-exposed workers, the beta2M-S level was significantly higher than in the nonexposed ones, with the exception of smokers. Results of the cross-week study confirm cumulative systemic effects of NOx on several examined biomarkers. SOD and GST were found to be depleted. A transient higher level of HA after a 5-d shift significantly inversely correlated with CC16 level. The data imply that NOx-depleted levels of CC16 are detectable already after an 8-h shift. Our results demonstrate that even low NOx human exposure can cause characteristic changes in bronchiolar epithelium cells and renal effects. Serum CC16 level, although a nonspecific marker, was lowest in NOx-exposed subjects. The most sensitive parameters in exposed workers were beta2M-S and a-tocopherol. Spirometric assessment was not useful to describe low occupational exposure to NOx. In studying the effects of NOx on biomarkers, it is essential to carefully select suitable time of sampling. Screening of CC16, beta2M-S, and a-tocopherol can be successfully employed for biological monitoring of exposure to NOx.

Adult↗

Blood concentration of essential trace elements and heavy metals in workers exposed to lead and cadmium.

The aim of the study was to determine blood concentration of essential trace elements (Se, Zn, Cu) and toxic metals (Pb, Cd), markers of antioxidant (activities of glutathione peroxidase (GPx), superoxidase dismutase and ceruloplasmin) and prooxidant processes (thiobarbituric acid reactive substances (TBARS)) in workers exposed to Pb and Cd. Forty three male workers of the lead-acid batteries department, aged 25-52 years, and twenty two workers, including 15 women, aged 36-51 years, exposed to Cd in the alkaline batteries department were examined. The reference group consisted of 52 healthy inhabitants of the same region. It was found that Se concentration and GPx activity in both erythrocytes and plasma of Cd exposed workers were significantly lower (p < 0.001) than in the reference group. We found an inverse linear correlation between blood Se and Cd concentrations in the workers exposed to Cd (r = -0.449; p < 0.01). Moreover, the activity of erythrocyte and plasma GPx was shown to be significantly lower in the study group of workers (p < 0.001). It was observed that TBARS concentration in plasma was significantly higher (p < 0.05) in the lead exposed workers than in the group without contact with Pb. Our results indicate that exposure to Pb and Cd affects the antioxidant potential of blood in workers exposed to heavy metals.

Adult↗

Sub-chronic inhalation toxicity of 1,2,4-trimethylbenzene (pseudocumene) in rats.

Toxic effects of exposure of 1,2,4-trimethylbenzene (pseudocumene) in the condition of sub-chronic inhalation experiment were examined. Rats were exposed to vapours of pseudocumene at concentrations of 123 mg/m3, 492 mg/m3 and 1230 mg/m3, 6 h/day, 5 days/week for 3 months. After 3 months of inhalation exposure animals were necropsied. Blood samples were obtained and selected organs were weighted and prepared for histological examinations. Sub-chronic inhalation exposure to pseudocumene resulted in an overall low degree of systemic toxicity. There were no changes in body weight gain, food consumption and absolute and relative organ weights. Slightly higher activity of sorbitol dehydrogenase was observed in male rats exposed to all concentrations applied. Some disturbances in hematological parameters characterised by decrease in red and increase in white blood cells were observed in male rats exposed to high concentration of 1230 mg/m3. The pulmonary lesions observed in male and female rats were statistically significant at mid and high concentrations of pseudocumene.

Air Pollutants↗

Subchronic inhalation toxicity of 1,2,3-trimethylbenzene (hemimellitene) in rats.

Toxic effects of exposure to 1,2,3-trimethylbenzene (hemimellitene) in the condition of subchronic inhalation experiment were examined. Rats were exposed to vapours of hemimellitene at concentrations of 123 mg/m3, 492 mg/m3 and 1230 mg/m3, 6 h/day, 5 days/week for 3 months. After termination of a 3-month inhalation, animals were necropsied. Blood samples were obtained and selected organs were weighed and prepared for histological examinations. Subchronic inhalation exposure to hemimellitene resulted in an overall, low systemic toxicity. There were no changes in body weight gain and food consumption. At a concentration of 1230 mg/m3, the increase in relative liver weight was observed in male rats. It was accompanied by slight increase in sorbitol dehydrogenase activity. The increase in alkaline phosphatase activity was found in females only. Some disturbances in haematological parameters, characterised by the decrease in red blood cells and slight increase in white blood cells, segmented neutrophils and lymphocytes were observed in rats at high exposure concentration of 1230 mg/m3. The pulmonary lesions as well as the increased number of goblet cells and interstitial lung parenchyma infiltration were noted in male and female rats from the highest exposure groups.

Alkaline Phosphatase↗

Studies on dermal, ocular and respiratory effects of 4-ethyltoluene in experimental animals.

The toxicity of 4-ethyltoluene to experimental animals was studied after single and repeated exposures. It was found that 4-ethyltoluene can be classified as a very mild skin and eye irritant. Sensory respiratory irritation of 4-ethyltoluene was studied in Balb/C male mice using the plethysmographic method. The concentration at which the respiratory rate decreased to 50% (RD50 value) was determined to be 4216 mg/m3 (2795-5850 mg/m3 for 95% confidence interval). To study repeated-dose inhalation toxicity, male and female outbred Wistar rats were exposed in a dynamic inhalation chamber to 4-ethyltoluene vapours at concentrations of 477 or 2337 mg/m3, 6 h/day, 5 days/week for 4 weeks (20 exposure days). No significant changes were observed in food consumption and body weight gain. Statistically significant, concentration-dependent changes in the number of total cells, as well as of macrophages, polymorphonuclear leucocytes and lymphocytes were found in bronchoalveolar lavage. In the fluid of bronchoalveolar lavage, a significant, concentration-related increase was noted in total protein and mucoproteins and the activity of beta-glucuronidase, gamma-glutamyl transferase, lactate dehydrogenase and acid phosphatase. Histopathology revealed an increased rate of bronchitis and pneumonia and perivascular lymphoid infiltrations in rats exposed to 2337 mg/m3 of 4-ethyltoluene.

Animals↗

DNA damage detected by the comet assay in the white blood cells of workers in a wooden furniture plant.

The study was aimed at the assessment of genotoxic effects in workers of a wooden furniture manufacture, based on the level of DNA damage in white blood cells (WBC). The alkaline single cell gel electrophoresis assay (known as the comet assay) in individual cells was adapted for detecting damaged DNA in WBC. The level of DNA damage was determined as the percentage of cells with comets. It was assessed in cells before and after incubation in RPMI 1640 medium and CO(2) at 37 degrees C for 1 h to repair DNA breaks. Thirty-five woodworkers and 41 control subjects were studied. In the woodworkers, significantly more cells with DNA damage (21.5%) were observed than in the control persons (9.7%). A slight but significant decrease in the level of DNA damage was found in the WBC of woodworkers after incubation (17.2%). Significantly higher levels of damaged DNA was observed in woodworkers who either smoked (22.1%) or did not smoke cigarettes (20.8%) than in smokers (13.2%) and non-smokers (7.0%) from the control group. After incubation, a slight decrease in the level of DNA damage was found in both smoking and non-smoking woodworkers compared to the respective subjects in the control group. The increased levels of DNA damage observed in the woodworkers could be associated with the occupational exposure to wood dust in the furniture manufacture.

Adult↗

Is it safe to apply the additivity rule to evaluating health effects of exposure to Farbasol?

Neurotoxic and sensory respiratory irritation effects of Farbasol in male rats and male Balb/C mice were investigated in condition of acute inhalation exposure. Rotarod performance and pain sensitivity behaviour were tested in rats exposed to Farbasol at concentrations of 4665-9622 mg/m3 immediately after termination of a four-hour exposure. The respiratory rate was measured in mice by the whole body plethysmographic method in 6 min duration exposure to various concentrations of Farbasol. Exposure to Farbasol resulted in concentration-dependent disturbances in rotarod performance and decrease in pain sensitivity in rats, and depression of respiratory rate in mice. The EC50 value for rotarod performance behaviour disturbances was 5497 mg/m3 and for pain sensitivity EC50 was 6589 mg/m3. The concentration depressing the respiratory rate to 50% (RD50) was 3139 mg/m3. The comparison of Farbasol EC50 and RD50 values and its individual constituents such as trimethylbenzene isomers and 4-ethyl toluene established in similar experimental conditions indicate their similar toxic effects potency. Application of additivity rule for establishing the MAC value for Farbasol seems to be safe.

Animals↗

DNA single-strand breaks and DNA repair in the lymphocytes of wooden furniture workers.

DNA single-strand breaks (DNA SSB) in peripheral lymphocytes of wooden furniture workers and a control group, including smokers and nonsmokers, were detected by the microfiltration method. Our results show that cigarette smoking significantly increases the fragmentation of DNA single strands in the wooden furniture workers (by nearly two times) but not in the control group. Moreover, occupational exposure to wood dust and other wooden plant substances significantly induced DNA SSB only in the lymphocytes of smokers (by about two times). DNA repair in the lymphocytes was investigated as 3H incorporation into DNA. High 3H incorporation in the unstimulated lymphocytes of both smoking and nonsmoking workers, as compared to the references, suggests that besides DNA SSB other DNA damage can be caused by occupational exposure in the wooden plant. Since DNA repair is not always perfect, the possibility is high that the low level of DNA repair in the study group may lead to irreversible DNA damage. We think that the workers exposed to wood dust and the substances emitted by furniture coating materials in the plant may be at higher risk for mutagenesis and/or carcinogenesis than the unexposed population.

Adult↗

Toxic effects of acute inhalation exposure to 1-methylnaphthalene and 2-methylnaphthalene in experimental animals.

Neurotoxic and sensory respiratory irritation effects of 1-methylnaphthalene and 2-methylnaphthalene in male rats and male Balb/C mice were investigated under conditions of acute inhalation exposure. Rotarod performance and pain sensitivity behaviour were tested in rats exposed to 1-methylnaphthalene at concentrations of 152-407 mg/m3, and 2-methylnaphthalene at concentrations of 229-522 mg/m3 immediately after termination of a four-hour exposure. The respiratory rate was measured in mice by the whole body pletysmographic method in 6 min duration exposure to various concentrations of 1-methylnaphthalene and 2-methylnaphthalene. Exposure to both methylated naphthalene derivatives resulted in concentration-dependent decrease in pain sensitivity in rats and depression of respiratory rate and mice. At the concentrations applied no statistically significant disturbances in rotarod performance behaviour were observed. The concentrations depressing the respiratory rate to 50% (RD50) were 129 mg/m3 and 67 mg/m3, for 1-methylnaphthalene and 2-methylnaphthalene, respectively. As based on RD50 values, the MAC values of 4 mg/m3 for 1-methylnaphthalene, and of 2 mg/m3 for 2-methylnaphthalene are suggested.

Administration, Inhalation↗

Occupational allergy to aldehydes in health care workers. Clinical observations. Experiments.

The incidence of allergy to aldehydes (formaldehyde, glutaraldehyde, glyoxal) was examined in 280 health care workers suffering from skin lesions. Allergy was diagnosed in 64 (22.8%) patients. The majority of them (85.9%) were sensitive only to 1 aldehyde. Formaldehyde caused allergy slightly more frequently (13.9%) than glutaraldehyde (12.4%). Only 5 (1.9%) patients were sensitive to glyoxal. The irritant effect of aldehydes to the rabbit eye and skin was tested by the Draize and OECD methods. Formaldehyde and glutaraldehyde showed stronger irritant effect than glyoxal. The sensitizing activity of aldehydes was also confirmed in guinea pigs (using the Maximization Test and the OECD methods). Formaldehyde showed the strongest and most persistent reactions. Significantly higher eosinophil and basophil counts were found in the blood samples of the sensitized guinea pigs. Cytotoxicity of glutaraldehyde and glyoxal was tested on mouse 3T3-L1 fibroblasts by the Neutral Red Uptake and MTT Reduction Assay. It was shown that both aldehydes were cytotoxic, and that the cytotoxic effect of glutaraldehyde was stronger than that of glyoxal.

Adult↗

[The evaluation of the irritating and sensitizing effects of benzalkonium chloride].

The aim of the study was to determine the threshold irritating effect of benzalkonium chloride on the rabbit's skin and eye, and its sensitizing effect on guinea pigs. The study was performed according to the OECD guidelines modified by Krysiak. As a threshold concentration of benzalkonium evoking slight inflammatory reaction on the skin in a single, closed exposure and in multiple, open exposure, the following values were adopted for its aqueous solutions: > 0.5-1%, and 05% respectively. Following the eye administration of 0.01% and 0.05% of benzalkonium aqueous solution a weak irritating and rapidly reversible effect was revealed. The study performed on guinea pigs indicated a sensitizing effect of 0.5%, 0.1% and 0.05% benzalkonium aqueous solutions. The effect differed depending on the concentration used. The evaluation covered the proportion of sensitized animals, the nature and intensity of dermal reaction, as well as peripheral blood eosinophil and basophil tests. The results showed that 0.1% benzalkonium aqueous solution is an optimum concentration for monitoring the sensitizing effect in humans being in contact with this substance.

Animals↗

The assessment of DNA damage in lymphocytes of wooden furniture workers.

Single-strand breaks (SSB) and DNA repair were detected in peripheral lymphocytes derived from workers of a furniture factory in a non-polluted region of Poland. The workers were exposed to wood dust (n = 19), or to the dust and varnishes or lacquers together (n = 5). Four groups were studied simultaneously: (a) exposed workers smokers of cigarettes (n = 14), (b) nonexposed smokers--control (n = 14), (c) exposed workers' nonsmokers (n = 14), (d) exposed nonsmokers (n = 10). In exposed workers DNA SSB and DNA repair were statistically significantly increased. DNA SSB was clearly higher in the smoking workers than in the smoking controls. Cigarette smoking itself has produced no evident increase in the frequency of DNA SSB in the control group. Occupational exposure had a significant effect on DNA repair in non stimulated lymphocytes both in smoking and nonsmoking workers.

DNA Damage↗

Toxic effects of acute inhalation exposure to 1,2,4,5-tetramethylbenzene (durene) in experimental animals.

Neurotoxic and sensory respiratory irritation effects of 1,2,4,5-tetramethylbenzene (durene) in male rats and male Balb/C mice were investigated in the condition of acute inhalation exposure. Rotarod performance and pain sensitivity behaviour were tested in rats exposed to durene at concentrations of 880, 1100 and 1280 mg/m3 immediately after termination of a four-hour exposure. The respiratory rate was measured in mice by the whole body pletysmographic method in a 6-min exposure to various concentrations of durene. Exposure to durene resulted in concentration-dependent decrease in pain sensitivity in rats and depression of respiratory rate in mice. At applied durene concentrations, no statistically significant disturbances in rotarod performance behaviour were observed. The concentration depressing the respiratory rate to 50% (RD50) was 838 mg/m3. As based on RD50 value, MAC of 25 mg/m3 is suggested for durene.

Administration, Inhalation↗

[Comparative studies on the usefulness of using a fixed dose and a stepwise method of dosing for evaluating acute chemical toxicity].

Following the studies on four compounds, classified in three different groups of toxicity, the validity of the up-down method and the fixed dose procedure was compared to classic Litchfield and Wilcoxon tests. The study was based rather on a very careful clinical observation than on the estimation of animal mortality as recommended in DL50 test. The study showed a considerable consistency between classic tests and the up-down method and the fixed dose procedure. But the determination of acute toxicity of chemical compounds by means of alternative methods proved to be highly humanitarian, and it required much lower number of less suffering animals.

Animal Testing Alternatives↗

Respiratory irritative effects of trimethylbenzenes: an experimental animal study.

Sensory respiratory irritation effects of trimethylbenzene isomers (TMBs) (hemimellitene, mesitylene and pseudocumene) in male Balb/C mice were investigated in conditions of acute exposure and in male Wistar rats in conditions of repeated 90-day inhalation exposure to pseudocumene. The pseudocumene, mesitylene and hemimellitene concentrations depressing the respiratory rate to 50% (RD50) were 578, 519, 541 ppm, respectively. Inhalation exposure to pseudocumene for 90 days increased the total number of cell macrophages, polymorphonuclear leukocytes and lymphocytes number at all three test concentrations compared with the controls. Total protein lactate dehydrogenase (LDH) and acid phosphatase activity in bronchoalveolar lavage (BAL) were significantly increased in all exposed groups. Based on the effects observed in the respiratory tract, the threshold limit value of at least 10 ppm should be considered for the occupational exposure to trimethylbenzene isomers.

Animals↗

The influence of atmospheric chromium on selenium content and glutathione peroxidase activity in blood of tannery workers.

The concentration of selenium and thiobarbituric acid reactive substances (TBARS) and activity of glutathione peroxidase (GSH-Px) were determined in blood of 34 workers of a tannery in Gniezno, Poland, who worked in an area containing chromium compounds. Fourteen workers were exposed to chromium compounds at concentrations of 0.11 +/- 0.07 mg Cr/m3 (mean +/- SD) and 20 at concentrations 5-10 times lower i.e., 0.022 +/- 0.009 mg Cr/m3. Excretion of Se in urine was measured in all of the investigated workers. Decreased Se concentration in whole blood and blood plasma and elevated TBARS concentration in blood plasma were found in the whole group of investigated tanners as compared to controls. Tanners working in areas with high chromium concentrations had a statistically significant decrease in Se concentration in blood and plasma and decreased urinary excretion of the microelement as compared with other tanners. TBARS concentration was 2.5 times lower in workers exposed to higher chromium concentrations (p < 0.005) than in other workers. Positive linear correlations were found between the concentration of Se in blood and the amount of the element excreted in urine (r = 0.48; p < 0.005), the concentration of Se in blood plasma and in urine (r = 0.46; p < 0.01), and the concentration of Se in blood and erythrocyte GSH-Px activity (r = 0.42; p < 0.02). The observed differences between Se concentration in blood and urine of tannery workers and people who are not employed in the industry may indicate a kind of specific adaptation of the body to the working environment containing chromium compounds.

Adult↗