[Analysis of volatile ingredients of selected essential oils listing relaxing action]. / Analiza lotnych skladników wybranych olejków eterycznych o dzialaniu relaksacyjnym.

BACKGROUND: Stress is a result of disturbed homeostasis and can contribute to the development of many diseases. One of the methods of combating stress is aromatherapy, which uses essential oils with a calming and relaxing effect. The aim of the work was to perform a qualitative analysis of selected essential oils with a relaxing effect. MATERIAL AND METHODS: The research concerned 6 preparations available on the Polish market, which are attributed with anti-stress activity. The qualitative analysis was carried out by gas chromatography with mass spectrometry, which allows the determination of both main and trace substances in the tested oils. The components of individual samples were compared with data from the literature. RESULTS: In the samples tested 9-36 substances were identified. The following substances had the largest share in the composition of the studied samples: limonene (0.5-91%), linalool acetate (16.8-39.2%), citronellal (0.1-28.7%), linalool (0.8-46.5%), valerianol (17.6%), geraniol (16.4%), and citronellol (14%). CONCLUSIONS: According to literature data, the main components of the studied essential oils have low acute toxicity. They can be safely used as intended and in the quantities recommended by the manufacturer. However, one should remember the potential synergistic effect (as a result of exposure to the abovementioned substances from various sources, such as: food, cosmetics, cleaning agents, etc.), as well as sensitizing effects of some compounds contained in oils. Despite the different chemical structure of active substances contained in the tested oils, it is suggested that the mechanism of the relaxing effect is identical and is associated with the inhibition of glutamatergic neurotransmission, similar to the action of benzodiazepines. Med Pr. 2019;70(2):229-47.

Prenatal toxicity and maternal-fetal distribution of 1,3,5,8-tetrachloronaphthalene (1,3,5,8-TeCN) in Wistar rats.

1,3,5,8-tetrachloronaphthalene (1,3,5,8-TeCN) is a Persistent Organic Pollutant (POP) that belongs to the group of polychlorinated naphthalenes (PCNs). The aim of the study was to investigate the maternal-fetal distribution and prenatal toxicity of 1,3,5,8-TeCN after its administration to pregnant Wistar rats during organogenesis. Radiolabeled 1,3,5,8-tetrachloronaphthalene-[ring-U-3H] was given by gavage at a dose of 0.3 mg per dam to evaluate its tissue distribution, and that of unlabeled 1,3,5,8-TeCN, at daily doses of 0.3, 1.0 or 3.0 mg kg b.w.-1 to assess prenatal toxicity. After a single administration of 1,3,5,8-TeCN, the highest concentration was detected in maternal adipose tissue. The concentration in the brain, uterus, kidneys, adrenals, ovaries, lungs and liver established in dams were two to nine times higher than in the maternal blood. 1,3,5,8-TeCN penetrated the blood-brain-barrier and the placenta. The results obtained from developmental toxicity indicate that 1,3,5,8-TeCN did not cause maternal toxicity and was not embryotoxic or teratogenic. However, fetotoxic effects were observed after non-toxic doses for dams (1.0 and 3.0 mg∙b.w.-1·day-1). 1,3,5,8-TeCN did not induce congenital skeletal defects but increased the number of fetuses with sternum ossification delay. After a dose of 3.0 mg kg b.w.-1·day-1, significantly more fetuses were found with enlargement of the renal pelvis: unilateral in female offspring and bilateral in male offspring. At the doses used, 1,3,5,8-TeCN, unlike hexachloronaphthalene, was not a CYP1A1 inducer.

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.

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.

[Comparison of chemical composition of selected essential oils used in respiratory diseases]. / Porównanie skladu chemicznego wybranych olejków eterycznych stosowanych w chorobach ukladu oddechowego.

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 ß-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.

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.

[ORGANOPHOSPHORUS FLAME RETARDANTS - TOXICITY AND INFLUENCE ON HUMAN HEALTH]. / FOSFOROWE ZWIAZKI ORGANICZNE ZMNIEJSZAJACE PALNOSC - TOKSYCZNOSC I WPLYW NA ZDROWIE LUDZI.

Organophosphorus flame retardants (flame retardants, FRs) have been used for several decades in many industries, including the production of dyes, varnishes, adhesives, synthetic resins, polyvinyl chloride, hydraulic fluids, plastics and textiles. Their importance in recent times has increased due to i.a., significantly reduced use of polybrominated diphenyl ethers (PBDEs) - persistent organic pollutants, dangerous for the environment. The aim of this study was to review the available literature data concerning phosphorous FRs primarily for neurotoxic, fertility, reproductive and carcinogenic effects. The analysis concerned the following most commonly used substances: tris(2-ethylhexyl)phosphate (TEHP), tris(2-butoxyethyl)phosphate (TBEP), triphenyl phosphate (TPP), tris(2-chloroethyl)phosphate (TCEP), tetrakis(hydroxymethyl)-phosphonium chloride (THPC), tributyl phosphate (TBP), tricresyl phosphate (TCP), tris(2-chloroisopropyl)phosphate (TCPP), tris(1,3-dichloroisopropyl)phosphate (TDCP) and tetrakis(hydroxymethyl)phosphonium sulphate (THPS). In animal studies neurotoxic effects were found after exposure to TBEP, THPC, TBP and TCP, while in humans they were observed only after exposure to TCP. TCEP, THPS, TBP, TCP and TDCP caused disorders in fertility and/or fetal development of animals. Adverse effects on reproduction in humans may be caused by TPP, TCP, and TDCP. In laboratory animals the development of tumors was observed after high doses of TEHP, TCEP, TBP and TDCP. None of these compounds is classified as a human carcinogen. The environmental toxicity of phosphate FRs is low (except for TPP, TCEP and TBEP). They are not stable compounds, in living organisms they are metabolised and quickly excreted. Therefore, they can be used as an alternative to PBDEs.

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

OBJECTIVES: Octabromodiphenyl 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 METHODS: Female 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. RESULTS: Administration (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. CONCLUSIONS: After 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.

Octabromodiphenyl ether - porphyrogenicity after repeated administration to rats.

OBJECTIVES: Octabromodiphenyl 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 METHODS: The 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. RESULTS: After 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.

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.

Porphyrogenic effect of pentabromodiphenyl ether after repeated administration to rats.

Until recently, pentabromodiphenyl ether (PentaBDE) was most commonly used as a flame retardant. On account of the hazardous effect of PentaBDE on the environment, its use was discontinued some years ago. The toxicity of this compound has been well documented in the literature, especially with regard to the endocrine system, induction of liver microsomal enzymes, and disturbance of redox homeostasis. The aim of this study was to investigate the porphyrogenic effect of PentaBDE after its repeated administration to rats at doses of 2, 8, 40, or 200 mg/kg/day. After a 28-day exposure, a dose-dependent increase (maximum 2.5-fold) in ALA-S activity in the liver was observed. The enhanced concentration of total porphyrins in the liver (3- to 19-fold after doses of 8-200 mg/kg/day) was also found. The most pronounced changes in liver concentrations of porphyrins were shown by high carboxylated porphyrins (a 19-fold increase for octacarboxyporphyrins and a 36-fold increase for heptacarboxyporphyrins). They made over 95% of total porphyrins accumulated in the liver. The porphyrogenic effect of PentaBDE was also evidenced by the augmented urinary excretion of total porphyrins. After 28 days of exposure, the observed changes (2- to 7-fold increase) were found to be dose-dependent. Tetracarboxyporphyrins predominated in urine; their urinary concentrations were 4-12 times higher, and their daily urinary excretion is 2-9 times higher. A dose of 2 mg/kg/day was the lowest dose that caused changes in the levels of porphyrins (LOAEL). The experiment revealed the effect of PentaBDE on the heme biosynthesis and porphyrin concentrations, which indicates its porphyrogenic effect.

Toxicity of penta- and decabromodiphenyl ethers after repeated administration to rats: a comparative study.

Until recently, pentabromodiphenyl (PentaBDE) and decabromodiphenyl (DecaBDE) ethers were commonly used as flame retardants in a wide array of products, mostly in the production of plastics utilized in the electric, electronic and textile industries. The aim of this study was to compare the toxicity of PentaBDE and DecaBDE after their repeated (7-28 days) intragastric administration to rats. The compounds were given at doses of 2, 8, 40 or 200 mg/kg/day (PentaBDE) and 10, 100 or 1,000 mg/kg/day (DecaBDE). The repeated administration of PentaBDE disturbed redox homeostasis, which was manifested by lower total antioxidant status and increased activity of glutathione reductase in serum and higher concentrations of glutathione reduced and malondialdehyde in the liver. The occurrence of these effects was not observed after DecaBDE administration. The results of histopathological examination showed fatty degeneration after administration of the highest dose of PentaBDE. The repeated administration of PentaBDE also caused the increase in relative liver mass, dose-dependent increase in the activity of CYP 1A (EROD) and CYP 2B (PROD), 7-12- and 2-8-fold, respectively, as well as enhanced level of CYP 1A1 (5-30-fold) and CYP 4A (2-4.5-fold). The administration of DecaBDE induced much less pronounced changes: a maximum 2.8-fold increase in the activity of CYP 1A, a twofold increase in CYP 2B, and no alterations in other parameters under study. Contrary to DecaBDE, PentaBDE disturbed redox homeostasis, and induced liver microsomal enzymes. Fatty degeneration in liver caused by this compound was also found.

Diterpenoid production in hairy root culture of Salvia sclarea L.

Growth and diterpenoid accumulation (salvipisone, ferruginol, aethiopinone and 1-oxoaethiopinone) during the growth cycle of a Salvia sclarea hairy root culture are described. The roots transformed by Agrobacterium rhizogenes (LBA 9402) were cultured in half-strength B5 liquid medium supplemented with 30 g L(-1) sucrose under light (16 h/8 h light/dark). A culture period of 30 days was optimal for both biomass and diterpenoid production. The total content of four diterpenoids in the hairy roots [(27.3 +/- 0.6) mg g(-1) dry weight] was higher than that of roots of field-grown S. sclarea plants [(3.15 +/- 0.15) mg g(-1) dry weight]. In transformed roots, aethiopinone was the main diterpenoid, whereas the principal diterpenoid of natural roots was salvipisone.

The effect of selected aromatic bromine derivatives on the activity of glutathione peroxidase and transferase.

OBJECTIVES: Glutathione (GSH) is an important element of antioxidative barrier. Its biological function consists in eliminating oxygen free radicals. It also acts as a co-substrate in numerous enzymatic reactions catalyzed by glutathione peroxidase (GPx) and glutathione S-transferase (GST). In our study we attempted to assess the effect of hexabromobenzene (HBB) and its metabolites on the level of GSH and related enzymes, GPx and GST. MATERIALS AND METHODS: The experiments were performed on female Wistar rats. The investigated compounds (HBB, 1,2,4,5-tetraBB, 1,2,4- and 1,3,5-triBB) were administered intragastrically in three different doses (HBB: 15, 75, and 375 mg/kg; 1,2,4,5-tetraBB and 1,2,4-triBB: 8, 40, and 200 mg/kg; 1,3,5-triBB: 12, 60, and 300 mg/kg) for 7, 14, 21 or 28 days. GSH level and activity of GST and GPx were determined in the obtained material. RESULTS: The highest activity of GPx and GSTwas observed after a 7-fold administration of all investigated compounds. Prolonged time of exposure caused the return to the control values. CONCLUSIONS: The study revealed that repeated exposure to aromatic bromine derivatives increases GPx and GST activity only in the initial phase of the experiment.

Effect of repeated administration of hexabromobenzene and 1,2,4,5-tetrabromobenzene on the levels of selected cytochromes in rat liver.

OBJECTIVES: Hexabromobenzene (HBB) is a flame retardant, which added to polymers, plastics, textiles, wood or paper, decreases the amount of carbon monoxide and heat release during fire. HBB is also formed as a result of decabromodiphenyl oxide pyrolysis or natural decabromobiphenyl ether debromination as the effect of photolysis. 1,2,4,5-Tetrabromobenzene (1,2,4,5-tetraBB) is a compound formed in the body as a metabolite of HBB. Both these compounds may appear in the environment and human tissue. The purpose of the study was to estimate the effect of repeated administration of HBB and 1,2,4,5-tetraBB on the levels of selected cytochromes in rat liver. MATERIALS AND METHODS: The investigated compounds were administered intragastrically in three different doses for 7, 14, 21 or 28 days. Relative liver mass was estimated as well as total concentration of cytochromes P-450 and EROD (CYP 1A) and PROD (CYP 2B) activity in rat liver. Concentration of cytochromes P-450 was determined in microsomal fraction (using the spectrometric method). EROD and PROD were detected by fluorimetric method. RESULTS: Repeated administration of 1,2,4,5-tetraBB and HBB (in the highest dose) was found to increase relative liver mass. After 1,2,4,5-tetraBB administration, total liver concentration of cytochromes P-450 increased even by several times, depending on the volume and number of doses. Less pronounced alterations were found after repeated administration of HBB. Exposure to HBB resulted in a tenfold increase in EROD activity (after 14-28 days) and a significantly lower increase in PROD activity. 1,2,4,5-TetraBB increased EROD activity by 2-3 times and PROD activity by maximum 2 times. CONCLUSIONS: Following the experiments, it may be stated that HBB and 1,2,4,5-tetraBB are inductors of microsomal enzymes system. 1,2,4,5-TetraBB more than HBB increases the level of total concentration of cytochromes and induces isoform CYP 2B (PROD). Administration of HBB resulted in the increase in CYP 1A (EROD) activity comparable to that after 3-methylcholanthrene.

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.