Elżbieta Bruchajzer

Acute and subacute nephrotoxicity of 2-bromophenol in rats.

The present report aims at providing broader information on the acute nephrotoxicity of 2-bromophenol (2-BP) (a bromobenzene (BB) metabolite), due to its action on the kidneys, after repeated administration. Investigations were performed on female rats. Following a single dose, the most pronounced changes involved: concentrations and rates of excretion of proteins in urine, the number of epithelial cells excreted in urine, creatinine and urea clearance and reduced glutathione in renal tissue. Immediate effects could be ascribed to both renal tubules and glomeruli, mirrored in the level of urinary proteins and intensified excretion of renal epithelial cells. Less pronounced changes of the indicator values were noted under repeated dosing of 2-BP. The results obtained in a single exposure study confirm earlier reports on the mild nephrotoxicity of 2-BP following exposure to high doses. However, the transition from single to repeated exposure does not result in enhanced nephrotoxicity.

The effect of short-term intoxication of rats with pentabromodiphenyl ether (in mixture mimic commercial products)

Until quite recently, pentabromodiphenyl ether (PentaBDE) was most commonly used as a flame retardant. Due to the considerably long atmospheric half-life of PentaBDE and its contribution to environmental pollution, it is categorized as a persistent organic pollutant (POP). As the data on the toxicity of PentaBDE is rather scarce, its potential acute toxicity was the subject of this study. PentaBDE was administered intragastrically to female rats, in a single dose (25, 200 or 2000 mg/kg b.w.). PentaBDE administered to rats disturbed redox homeostasis, which was manifested by lower total antioxidant status (TAS) in serum and by higher liver glutathione reduced (GSH) concentration. The toxic effect of PentaBDE intensified lipid peroxidation. On histopathological examination, administration of the highest PentaBDE dose (2000 mg/kg b.w.) was seen to induce symptoms of fatty liver. PentaBDE caused an increase in relative liver mass, cytochromes P-450 (after two highest doses), a dose-dependent increase in the activity of CYP lA (12—26 fold) and CYP 2B (5—6 fold) as well as the levels of CYP lAl (16—50 fold) and CYP 4A (2—3 fold) in liver.

Octabromodiphenyl ether — porphyrogenicity after repeated administration to rats

ObjectivesOctabromodiphenyl ether (OctaBDE) is a flame retardant which has been withdrawn from common use due to its negative effect on the environment. The literature data regarding its toxicity addresses its effect on liver function, the endocrine and reproductive systems, as well as its developmental toxicology aspects. The aim of this study was to investigate the effect of repeated administration of OctaBDE on heme biosynthesis in rats.Materials and MethodsThe study was performed on female Wistar rats. OctaBDE was administered intragastrically at four different doses (2, 8, 40 or 200 mg/kg/day) for 7, 14, 21 or 28 days. The following measures of heme synthesis disturbance were used: urinary excretion of porphyrins, liver concentration of porphyrins, the activity of delta-aminolevulinate synthase (ALA-S) and delta-aminolevulinate dehydratase (ALA-D) in the liver.ResultsAfter 28 days of exposure, lower ALA-S and ALA-D activity was observed in the liver. Additionally, increased concentrations of high carboxylated porphyrins (octa- and heptacarboxyporphyrins) were found in the liver: from 2- to 10-fold after the 2 mg/kg/day doses and from 4- to 14-fold after the 8-200 mg/kg/day doses. The porphyrogenic effect of OctaBDE was also evidenced by augmented, dose-dependent and exposure time-dependent, concentrations of total porphyrins in urine (2–7.5-fold increase) and their urinary excretion (2-9-fold increase). Tetracarboxyporphyrins predominated in the urine; their concentrations increased 2.5–10 fold. Conclusions: The study revealed that repeated exposure to OctaBDE affects heme biosynthesis and the levels of porphyrins. The lowest effective level which induced changes in porphyrin concentration was 2 mg/kg/day.

Developmental toxicity of hexachloronaphthalene in Wistar rats. A role of CYP1A1 expression.

Hexachloronaphthalene (HxCN) is one of the most toxic congeners of polychlorinated naphthalenes (PCNs). This study assesses the prenatal toxicity of HxCN after daily administration at doses of 0.1-1.0mg/kg b.w. to pregnant Wistar rats during organogenesis. We evaluated also the expression of CYP1A1 mRNA and protein in the livers of dams and fetuses, as well as the placenta. The results indicate that 0.3mg/kg b.w. was the lowest HxCN toxic dose for dams (LOAEL) while a dose of 0.1mg/kg b.w. was sufficient to impair the intrauterine development of embryos/fetuses without maternal toxicity. Regardless of the applied dose, HxCN generated embryotoxic effects. Dose-dependent fetotoxic effects were associated with HxCN exposure. HxCN was found to be a strong inducer of maternal and fetal CYP1A1. Expression of CYP1A1 mRNA in the placenta appears to be the most sensitive marker of HxCN exposure.

The effects of hexachloronaphthalene on selected parameters of heme biosynthesis and systemic toxicity in female wistar rats after 90-day oral exposure

Hexachloronaphthalenes (HxCNs) are the most toxic congeners of polychlorinated naphthalenes, a group of compounds lately included into the list of persistent organic pollutants (POPs). This study presents the effects of 90‐day intragastric administration of HxCN to female Wistar rats at doses of 0.03, 0.1, and 0.3 mg/kg body weight. The study examined selected parameters of the heme synthesis pathway, oxidative stress, hepatic cytochromes level, and basic hematology indicators. A micronucleus test was also performed. The subchronic exposure of rats to HxCN resulted in disruption of heme biosynthesis, hematological disturbances, and hepatotoxicity. The highest dose of HxCN inhibited aminolevulinic acid dehydratase (ALA‐D) and uroporphyrinogen decarboxylase (URO‐D). Accumulation of higher carboxylated porphyrins in the liver and increased excretion of 5‐aminolevulinic acid in the urine was observed after a dose of 0.1 mg/kg body weight. The most sensitive effect of HxCN in rats was very strong induction of hepatic CYP1A1 activity, which was observed after the lowest dose. The highest dose of HxCN induced significant thrombocytopenia, thymic atrophy and hepatotoxicity, expressed as hepatomegaly and hepatic steatosis.

Hexachloronaphthalene (HxCN) as a potential endocrine disruptor in female rats

Hexachloronaphthalene (HxCN) is one of the most toxic and most bioaccumulative congeners of polychlorinated naphthalenes (PCNs) known to be present in animal and human adipose tissue. Unfortunately, little data is available regarding the negative effect of PCNs on endocrine function. The aim of the study was to investigate the direct influence of subacute (two and four-week) and subchronic (13-week) daily oral exposure of female rats to 30, 100 and 300 μg kg b.w.-1 HxCN on ovarian, thyroid function and neurotransmitters level. The levels of selected sex hormones (progesterone: P and estradiol: E2) in the serum and uterus, regularity of estrous cycle, levels of thyroid hormones (fT3 and fT4), TSH, γ-aminobutyric acid and glutamate levels in selected brain areas and the activity of CYP1A1 and CYP2B in the liver were examined. Estrogenic action (elevated E2 concentration in the uterus and serum) was observed only after subacute exposure, and antiestrogenic activity (decreased E2 level and uterus weight) after 13 weeks administration of 300 μg kg b.w.-1 day-1. Subchronic administration of HxCN significantly lengthens the estrous cycle, by up to almost 50%, and increases the number of irregular cycles. In addition, increased TSH and decreased fT4 serum levels were observed after all doses and durations of exposure to HxCN. Only subacute exposure led to a significant decrease in the level of examined neurotransmitters in all analyzed structures. Additionally, exposure to low doses of HxCN appears to lead to strong induction of CYP1A1 in a liver. It can be hypothesized that HxCN produces effects which are very similar to those caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and dioxin-like compounds (DLCs), particularly concerning endocrine and estrous cyclicity disorders. Therefore, HxCN exposure may exert unexpected effects on female fecundity among the general population.

Comparison of chemical composition of selected essential oils used in respiratory diseases

BACKGROUND Essential oils are fragrances extracted from plants. They have a smooth consistency and pleasant smell. Essential oils have been applied in aromatherapy, cosmetics, food and pharmaceutical products. The aim of the study was to analyze the composition of selected essential oils used in respiratory diseases. MATERIAL AND METHODS The qualitative analysis was performed by gas chromatography with mass spectrometry. For the study 6 essential oils available in Polish shops and used in various respiratory diseases were chosen. The results were compared with the information provided by the manufacturer and the literature. RESULTS The method used in the presented work allowed to qualitatively identify the main components in studied essential oils. In the analyzed samples generally occurred: α- i β-pinene, limonene, terpinen-4-ol and caryophyllene. In addition to limonene, the presence of linalool, eugonol and geraniol, potentially allergenic substances, were also detected. CONCLUSIONS The qualitative composition of the studied essential oils comply with the existing literature data. Their main ingredients show antimicrobial and antiviral activities, therefore they are used to eradicate the symptoms of infection. However, the attention should be paid to the composition of the products because they often comprise potential allergens. Information on the presence of such a substance in the preparation should be clearly marked by the manufacturer on the packaging. Fragrances are also found in a number of household products that increase their concentration in the air of living premises, thereby increasing the risk of side effects especially in people with allergies or sensitive. Med Pr 2018;69(2):167-178.

Selected oxidative stress parameters after single and repeated administration of octabromodiphenyl ether to rats.

ObjectivesOctabromodiphenyl ether (OctaBDE) was used as a flame retardant applied mostly in the manufacture of plastics utilized in the electrical and electronic industries. Owing to its long half-life and being regarded as an environmental pollutant, OctaBDE, like other polybrominated diphenyl ethers, has been classified as a persistent organic pollutant (POP). This study was carried out to assess the effects of oxidative stress (redox homeostasis) induced in rats by OctaBDE.Material and MethodsFemale Wistar rats exposed intragastrically to OctaBDE at single (25, 200 or 2000 mg/kg b.w.), or repeated (0.4, 2, 8, 40 or 200 mg/kg/day) doses during 7–28 days were used in the experiment. Selected oxidative stress parameters were determined in the liver and blood serum.ResultsAdministration (single or repeated) of OctaBDE to rats resulted in the impaired redox homeostasis, as evidenced by the increased levels of reduced (GSH) and oxidized (GSSG) glutathione in the liver, the reduced total antioxidant status (TAS) in serum and the increased concentration of malondialdehyde (MDA) in the liver. After multiple doses of OctaBDE, elevated activity of glutathione transferase (GST) in the liver was also noted.ConclusionsAfter repeated administration of OctaBDE at the lowest dose (0.4 mg/kg/day), changes were observed in the parameters (MDA, TAS, GSSG) indicative of oxidative stress.