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Hexachloronaphthalene (PCN67) is one of the most toxic among polychlorinated naphthalenes. Despite the known high bioaccumulation and persistence of PCN67 in the environment, it is still unclear to what extent exposure to these substances may interfere with normal neuronal physiology and lead to neurotoxicity. Therefore, the primary goal of this study was to assess the effect of PCN67 in neuronal in vitro models. Neuronal death was assessed upon PCN67 treatment using differentiated PC12 cells and primary hippocampal neurons. At 72 h postexposure, cell viability assays showed an IC50 value of 0.35 μg/ml and dose-dependent damage of neurites and concomitant downregulation of neurofilaments L and M. Moreover, we found that younger primary neurons (DIV4) were much more sensitive to PCN67 toxicity than mature cultures (DIV14). Our comprehensive analysis indicated that the application of PCN67 at the IC50 concentration caused necrosis, which was reflected by an increase in LDH release, HMGB1 protein export to the cytosol, nuclear swelling, and loss of homeostatic control of energy balance. The blockage of mitochondrial calcium uniporter partially rescued the cell viability, loss of mitochondrial membrane potential (ΔΨm), and the overproduction of reactive oxygen species, suggesting that the underlying mechanism of neurotoxicity involved mitochondrial calcium accumulation. Increased lipid peroxidation as a consequence of oxidative stress was additionally seen for 0.1 μg/ml of PCN67, while this concentration did not affect ΔΨm and plasma membrane permeability. Our results show for the first time that neuronal mitochondria act as a target for PCN67 and indicate that exposure to this drug may result in neuron loss via mitochondrial-dependent mechanisms.

Cadmium (Cd) is an environmental toxicant and endocrine disruptor in humans and animals, and recent studies have illustrated that the uterus is exceedingly sensitive to Cd toxicity. The aim of the study was to investigate the influence of subchronic (90 days) oral Cd exposure in daily doses of 0.09-4.5 mg/kg b.w. on the balance of sex hormones by estimating estradiol (E2) and progesterone (P) concentrations in the uterus and plasma in comparison with the effects of 17β-E2. Additionally, the uterine weight, histopathological changes in the uterus and ovaries, the regularity of the estrous cycle, Cd bioaccumulation in uterine tissue, and selected biochemical parameters of oxidative stress were determined. A long period of observation (three and six months following the administration period) was used to assess whether the existing effects are reversible. The lowest dose of Cd caused effects similar to 17β-E2: an increase of E2concentration in the uterus, endometrial epithelium thickness, and disturbed estrous cycle with estrus phase prolongation. The obtained results suggest that Cd causes nonlinear response. Higher doses of Cd caused a significant decrease in E2concentration in the uterus and plasma, estrous cycle disturbances, endometrium atrophy, and structural damage in the ovaries. This dose additionally induces lipid peroxidation in the uterine tissues. It is noteworthy that a prolonged time of observation after terminating the exposure showed persistent changes in the concentration of E2in uterine tissue, as well as alterations in estrous cycle phases, and an increase in lipid peroxidation in the uterus. Moreover, significant positive correlations between the plasma E2concentration and endometrial epithelium thickness in all studied groups were found. In summary, subchronic oral Cd exposure of female rats may result in impaired fertility processes.

Cadmium (Cd) is an environmental pollutant known to pose a public health issue. The mechanism of Cd toxicity on the uterus, including the protective role of metallothionein (MT), is still not fully understood. The aim of the study was to evaluate the degree of MT-Cd binding in the uterus of rats exposed per os to Cd at daily doses of 0.09, 0.9, 1.8 and 4.5 mg Cd/kg b.w. for 90 days. To assess the permanence of the bond, the rats were observed over long observation periods: 90 and 180 days after termination of exposure. Additionally, uterine concentration of Zn, Cu, Ca, Mg was determined. Cd leads immediately after exposure to a max. 30-fold increase in the concentration of Cd in the uterus, with only small amounts being bound to MT. After 90 days following termination of exposure, and especially after 180 days, an increase in MT-Cd concentration was noted for the three highest doses; even so, the degree of Cd binding by MT was still small. Additionally, the accumulation of Cd in the uterus disturbs the homeostasis of determined essential elements, manifested by a significant increase in Cu concentration and a decrease in Zn, Mg and Ca, especially 180 days after termination of exposure. The obtained results indicate that MT has only a slight protective role in the uterus and that Cd ions may have harmful effects not related to MT: directly on the uterine tissue, and indirectly by disturbing the homeostasis of its essential elements.

The legacy of polychlorinated naphthalenes (PCNs) manufactured during the last century continues to persist in the environment, food and humans. Metrological advances have improved characterisation of these occurrences, enabling studies on the effects of exposure to focus on congener groups and individual PCNs. Liver and adipose tissue show the highest retention but significant levels of PCNs are also retained by the brain and nervous system. Molecular configuration appears to influence tissue disposition as well as retention, favouring the higher chlorinated (≥ four chlorines) PCNs while most lower chlorinated molecules readily undergo hydroxylation and excretion through the renal system. Exposure to PCNs reportedly provokes a wide spectrum of adverse effects that range from hepatotoxicity, neurotoxicity and immune response suppression along with endocrine disruption leading to reproductive disorders and embryotoxicity. A number of PCNs, particularly hexachloronaphthalene congeners, elicit AhR mediated responses that are similar to, and occur within similar potency ranges as most dioxin-like polychlorinated biphenyls (PCBs) and some chlorinated dibenzo-p-dioxins and furans (PCDD/Fs), suggesting a relationship based on molecular size and configuration between these contaminants. Most toxicological responses generally appear to be associated with higher chlorinated PCNs. The most profound effects such as serious and sometimes fatal liver disease, chloracne, and wasting syndrome resulted either from earlier episodes of occupational exposure in humans or from acute experimental dosing of animals at levels that reflected these exposures. However, since the restriction of manufacture and controls on inadvertent production (during combustion processes), the principal route of human and animal exposure is likely to be dietary intake. Therefore, further investigations should include the effects of chronic lower level intake of higher chlorinated PCN congeners that persist in the human diet and subsequently in human and animal tissues. PCNs in the diet should be evaluated cumulatively with other similarly occurring dioxin-like contaminants.

Among polychlorinated naphthalenes (PCNs), listed by the Stockholm convention as Persistent Organic Pollutants (POPs), hexachloronaphthalenes are considered the most toxic and raise the highest concern. Of these, 1,2,3,5,6,7-hexachloronaphthalanene (PCN67) is considered the main congener affecting human health due to its hepatotoxicity and its ability to disturb the reproductive, endocrine, and hematological systems. It is also prevalent in human serum/plasma, milk, and adipose tissue. However, little is known about its neurotoxicity, despite the fact that anorectic effects have been observed in workers occupationally exposed to PCNs and in animal research on PCN67. Since dopamine is involved in many aspects of food intake, the aim of this study was to confirm whether PCN67 affects dopamine synthesis in differentiated PC12 cells, a widely used model of neurosecretion. Our results show that exposure to PCN67 resulted in diminished dopamine content and release. Moreover, PCN67 also affected the expression of tyrosine hydroxylase and lowered the expression of vesicular monoamine transporter 1 (VMAT1). In addition, significantly lower expression of antioxidant enzymes, including catalase, glutathione peroxidase and copper/zinc superoxide dismutase, was observed in comparison to the vehicle. In conclusion, PCN67 appears to disturb dopaminergic transmission by altering tyrosine hydroxylation, reducing VMAT1 expression and impairing antioxidant protection. Our study provides a potential mechanism for how PCN67 may cause dopamine deficiency and contribute to neuronal death by affecting cellular antioxidant potency; however, this conclusion requires further research.

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.

Background: Zinc (Zn) and selenium (Se) play a well-documented role in cancer prevention (e.g., for prostate cancer), and their combined supplementation is often given as a recommended prophylactic agent. The aim of the study was to determine the influence of Zn and/or Se supplementation on the androgen receptor (AR) in the prostate lobes and the serum selected hormone concentrations, a hitherto unresearched topic. Methods: Male rats (n = 84) were administered with Zn and/or Se intragastrically for up to 90 days. The effects of administration on the tested parameters were checked after 30 and 90 days of administration and additionally, 90 days after the end of 90 day administration. Results: Zn alone leads to an increase in serum testosterone concentrations, while the protein expression of AR in both parts of the prostate increases. Combined administration of Zn and Se eliminates the effect of Zn, which may suggest that these two elements act antagonistically. Se supplementation alone results in the same level of AR protein expression in administration and 90 days after administration periods. Conclusion: This paper presents the first report of the influence of Zn and/or Se supplementation on the protein expression of AR in the prostate. Our findings seem to indicate that simultaneous supplementation of both elements may be ineffective.

Cadmium (Cd) is regarded as a potential endocrine disruptor. However, the exact mechanism by which this metal may interfere with the reproductive system has not yet been elucidated. The present study aimed to investigate the effect of subacute Cd oral administration at daily doses of 0.09, 1.8, and 4.5 mgCd/kg b.w. and the impact of Cd on sex hormones (estradiol (E2) and progesterone (P)) in the plasma and uterus, as well as on estrous cyclicity and histopathological changes in uterine and ovary in female rats after terminating the exposure and after a prolonged observation period (3 months). Moreover, Cd bioaccumulation in the uterine and brain tissue of rats was analyzed. The study revealed that oral Cd exposure induced changes in the plasma levels of steroid hormones: decrease in E2 and increase in P after the highest dose of Cd. Probably, for the first time, it was evidenced that circulation sex hormone disturbances in Cd-exposed rats caused irregular estrous cycle, persisting for 3 months after exposure termination; no alterations in these hormone levels in uterine tissue were noted. Cd did not induce estradiol-like hyperplasia of endometrium, but resulted in endometrial edema irrespective of the dose, and caused damage of the ovaries after the highest dose. In summary, subacute oral exposure of female rats to Cd may lead to long-term disturbances in reproductive system.

Although Persistent Organic Pollutants (POPs) are some of the most dangerous environmental toxicants, data on their impact on hemostasis are virtually limited. 1,2,3,5,6,7-hexachloronaphthalene (PCN67) seems to be one of the most toxic congeners of polychlorinated naphthalenes (PCNs), which have recently been listed as POPs. The toxic effects of PCNs are similar to other chlorinated aromatics, e.g. polychlorinated dibenzo-p-dioxins (PCDDs), so an impact on hemostasis could not be excluded. Therefore, this study examines, for the first time, if short-term (two and four weeks) exposure of a mixture of hexachloronaphthalene congeners with a PCN67 as a predominant component to female Wistar rats may have an impact on selected hemostasis parameters, such as overall potential and kinetic parameters of clot formation and fibrinolysis; hematology and basic coagulology parameters. It also examines the influence of PCN67 on the stability of erythrocyte membranes. Obtained results indicate that PCN67 may be an important disturbing factor regarding both coagulation and fibrinolysis processes, as well as platelet count. Exposure to PCN67 significantly affected clot formation and lysis processes and diminished fibrinogen concentration after both administration periods. After two weeks of administration, an increased activated partial thromboplastin time (APTT) was noted; after four weeks - decreased platelet count with concomitant increased in mean platelet volume. Moreover, PCN67 may exert adverse effects on the red blood cells membrane stability, which were manifested by a statistically significant increase of red blood cells lysis.

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.

Objectives Due to structural and toxicological similarities to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated naphthalenes (PCNs) were included in the Stockholm Convention on Persistent Organic Pollutants (POPs) in 2015. Hexachloronaphthalene (HxCN) is considered to be one of the most toxic congeners of PCNs. The objective of this study was to determine the maternal and fetal tissue concentrations of hexachloronaphthalene after a single administration. Material and methods Pregnant female Outbred Wistar rats were used for the study. The [14C]-HxCN was administered in a single oral dose of 0.3 mg/rat (150 kBq/rat) on gestational day 17 (GD17), GD18 or GD19. All dams were sacrificed on GD20. The blood and selected tissue samples taken from mothers and fetuses 24 h, 48 h or 72 h after exposure were evaluated for the distribution of HxCN. Results Maximum concentrations of HxCN in pregnant rats were found in the liver and adipose tissue. Relatively high levels of HxCN were also reported in the spleen, ovaries, adrenal glands and uterus, as well as in the sciatic nerve, brain and kidneys. Hexachloronaphthalene penetrates through the blood-brain barrier (BBB), as evidenced by twice the concentration in the brain compared to the blood concentration, and through the placental barrier, as indicated by the level of maternal-fetal compartment (placenta, amniotic fluid, litter). Among the examined fetal tissues, the highest levels of HxCN were found in the kidneys and in the brain. The concentrations in these organs were higher than that found in the maternal blood. Conclusions This paper is the first to detail the concentrations of HxCN in the maternal tissues and the transplacental transfer of the tested compound to the fetuses. The exposure of pregnant rats to HxCN results in its accumulation in the maternal liver, fat tissue, reproductive and nervous system, and particularly in the fetal brain. This demonstrates both the effective absorption and significant systemic accumulation which could lead to negative health implications. Int J Occup Med Environ Health 2018;31(5):685-695.

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. Medical University of Lodz, Poland, Grant Numbers: 503/3-045-01/503-31-001, 502-03/3-045-01/502-34-044

Glutamate (Glu) and γ-aminobutyric acid (GABA) are the main neurotransmitters in the central nervous system for excitatory and inhibitory processes, respectively. Monitoring these neurotransmitters is an essential tool in establishing pathological functions, among others in terms of occupational exposure to toxic substances.We present modification of the HPLC (high-performance liquid chromatography) to the UPLC (ultra-performance liquid chromatography) method for the simultaneous determination of glutamate and γ-aminobutyric acid in a single injection. The isocratic separation of these neurotransmitter derivatives was performed on Waters Acquity BEH (ethylene bridged hybrid) C18 column with particle size of 1.7 μm at 35°C using a mobile phase consisting of 0.1 M acetate buffer (pH 6.0) and methanol (60:40, v/v) at a flow rate of 0.3 ml/min. The analytes were detected with the fluorescence detector (FLD) using derivatization with o-phthaldialdehyde (OPA), resulting in excitation at 340 nm and emission at 455 nm.Several validation parameters including linearity (0.999), accuracy (101.1%), intra-day precision (1.52-1.84%), inter-day precision (2.47-3.12%), limit of detection (5-30 ng/ml) and quantification (100 ng/ml) were examined. The developed method was also used for the determination of these neurotransmitters in homogenates of selected rat brain structures.The presented UPLC-FLD is characterized by shorter separation time (3.5 min), which is an adaptation of the similar HPLC methods and is an alternative for more expensive references techniques such as liquid chromatography coupled with tandem mass-spectrometry (LC-MS/MS) methods. Med Pr 2017;68(5):583-591.Glutamate (Glu) and γ-aminobutyric acid (GABA) are the main neurotransmitters in the central nervous system for excitatory and inhibitory processes, respectively. Monitoring these neurotransmitters is an essential tool in establishing pathological functions, among others in terms of occupational exposure to toxic substances.We present modification of the HPLC (high-performance liquid chromatography) to the UPLC (ultra-performance liquid chromatography) method for the simultaneous determination of glutamate and γ-aminobutyric acid in a single injection. The isocratic separation of these neurotransmitter derivatives was performed on Waters Acquity BEH (ethylene bridged hybrid) C18 column with particle size of 1.7 μm at 35°C using a mobile phase consisting of 0.1 M acetate buffer (pH 6.0) and methanol (60:40, v/v) at a flow rate of 0.3 ml/min. The analytes were detected with the fluorescence detector (FLD) using derivatization with o-phthaldialdehyde (OPA), resulting in excitation at 340 nm and emission at 455 nm.Several validation parameters including linearity (0.999), accuracy (101.1%), intra-day precision (1.52–1.84%), inter-day precision (2.47–3.12%), limit of detection (5–30 ng/ml) and quantification (100 ng/ml) were examined. The developed method was also used for the determination of these neurotransmitters in homogenates of selected rat brain structures.The presented UPLC-FLD is characterized by shorter separation time (3.5 min), which is an adaptation of the similar HPLC methods and is an alternative for more expensive references techniques such as liquid chromatography coupled with tandem mass-spectrometry (LC-MS/MS) methods. Med Pr 2017;68(5):583–591.

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.

Polychlorinated naphthalenes (PCNs), including hexachloronaphthalene (HxCN), are widespread global environmental contaminants. Our experiments were aimed at assessing HxCN effects on motor behavior, long-term memory, pain sensitivity, magnitude of stress-induced analgesia, auditory function and sensorimotor gating, following repeated intragastric administration (28 days) of HxCN at 0.3 and 1.0 mg/kg body weight. Three weeks after the exposure termination, male Wistar rats were subjected to the neurobehavioral tests battery performed in the following order: open-field test, passive avoidance test, hot-plate test and acoustic startle response test. Repeated administration of HxCN induced disorders of motivational processes manifested by: anorectic effect caused by aphagia and adipsia; significantly reduced motor activity (hypokinesia); impaired long-term memory and acquired passive avoidance reaction; reduced pain threshold and shortened duration of anxiety reaction after pain stimulus (sensory neglect). Some of these neurobehavioral effects (impaired long-term memory, reduced pain threshold and stress-induced analgesia) were observed at 0.3 mg HxCN/kg body weight without any signs of overt toxicity. The outcome of our study shows that HxCN, like other compounds of the persistent organic pollutants (POPs) group, creates a potential risk of behavioral changes in the central nervous system in the general population as a result of environmental exposure.

The aim of the study was to assess the maternal toxicity of polychlorinated naphthalenes (PCNs) and embryotoxic, fetotoxic, and teratogenic effects after administration of the PCN mixture to pregnant rats in four (0.3-9.0 mg/kg bw) daily doses during organogenesis (days 6-15 of gestation). For dams, a dose of 0.3 mg/kg bw, administered during organogenesis, has been established as NOAEL of PCNs, and a dose of 1 mg/kg bw, administered in the same period, as LOAEL. The dose-related fetotoxic (reduced body weight and length of the fetus, extension of renal pelvis and lateral brain ventricles, signs of delayed ossification and retardation in development of internal organs), and teratogenic effects (cleft palate and hydronephrosis) were recorded at all dose levels, also at the dose non-toxic to mothers. PCNs have been concluded to be potent fetotoxic and teratogenic agents producing similar effects to those of other toxic dioxin-like compounds.

The aim of the study was to investigate the toxicity of hexachloronaphthalene (HxCN) and its effect on cytochrome P-450 in rats and to make a comparison between HxCN and tetrachloronaphthalene (TeCN), an inactive congener. Our study provided evidence that the anorectic effect, with concurrent significant increase in relative liver mass was the most spectacular symptom of the toxic effect of hexachloronaphthalene in the rats after its single (250 mg/kg) and repeated (1 and 10 mg/kg) administration. Regardless of the kind of the experiment (acute or subacute toxicity), dose-dependent increase in lipid peroxidation in the liver was also observed, which may indicate that HxCN most probably generates oxidative stress in this organ. It was also observed that HxCN is a very strong inducer of cytochrome P-450, especially of CYP 1A, which is the most sensitive biomarker of exposure to this congener. In this study, LOAEL is 1 mg HxCN/kg b.w.

The aim of the study was to investigate the subacute toxicity of a polychlorinated naphthalene (PCN) mixture and its effect on cytochrome P-450 levels in rats. The animals were administered PCNs intragastrically in repeated daily doses of 1, 10, and 100 mg/kg. The animals were dissected after 7, 14, or 21 doses. Doses of 10 and 100 mg/kg induced a significant decrease in the body weight at all time points of the experiment compared with the control group. The exposure to PCNs increased both the level of total cytochrome P-450 and the activity of CYP 1A at the same time points. In the groups of rats given PCNs in doses of 10 and 100 mg/kg, an evident dose- and time-dependent increase in malondialdehyde (MDA) level was observed throughout the experiment. The correlation between the increased MDA and decreased glutathione (GSH) levels in the liver was also observed.

Polychlorinated naphthalenes (PCNs) are able to induce cytochrome P-450-dependent microsomal monooxygenase activities in vivo and in vitro. The aim of this study was to investigate the toxicity of a PCN mixture, and its effect on the levels of cytochrome P-450 in rats. The animals were intragastrically administered a mixture of PCNs in single doses of 250, 500 and 1000 mg/kg b.w. Dissection of animals was performed 24, 72 and 240 hours after administration. After PCN administration (all doses) the body weight loss (up to 30% in comparison with the control group, 240 hours after administration) and an increase of relative liver mass (about 126 - 153% of controls, 72 hours after administration) were observed. The exposure to PCN evoked an increase in the level of total cytochrome P-450 as well as the activity of CYP 1A (mediated 7-ethoxyresorufin O-deethylation) at all time points. The maximum activity of CYP 1A (about 12-to 15-fold increase in comparison with the control group) was observed 72 hours after dosing. Malondialdehyde (MDA), determined in the liver, showed a high increase and 240 hours after administration, the level of MDA was about one order of magnitude greater in comparison with control.

The study was undertaken to explore whether cadmium bioaccumulation can induce oxidative stress in the uterus of rats. Cadmium (0.09, 0.9, 1.8 or 4.5mgCd/kg b.w.) was administered by gavage for 28 days. The animals were dissected on the first day and then after 90 days post exposure (second group of animals). The results show that cadmium accumulates in the uterus in a dose-dependent manner. The uterine Cd concentrations were almost the same in both groups, which is indicative of its long half-life in this organ. The accumulated cadmium caused significant changes in catalase (CAT) activity and lipid peroxidation (MDA) levels at concentrations from 0.09 to 0.35μgCd/g wet uterine tissue. In summary our results show that the induction of oxidative stress and lipid peroxidation in the uterus may play important roles in the mechanism of toxicity in this organ and may have a negative impact on reproductive processes.

The normal human prostate accumulates the highest levels of zinc (Zn) of any soft tissue in the body. The pool of zinc available to the body is known to significantly decrease with age. It is suggested that dietary Zn supplementation protects against oxidative damage and reduces the risk of cancer. Zinc sulfate and zinc gluconate were the most frequently mentioned in per os administration in studies on Zn supplementation. The major aim of the study was to compare the bioavailability of different Zn compounds (sulfate, gluconate and citrate) in the prostate after their daily administration to male rats at three different doses (3.0; 15.0; and 50.0 mg Zn/kg b.w.) for 30 days. The results show that bioavailability in the prostate differs significantly between individual zinc preparations. A significantly elevated Zn concentration in the dorso-lateral lobe of the prostate, compared to controls, was found in the rats supplemented with two compounds only: zinc gluconate and zinc citrate. However, after administration of zinc gluconate, this effect occurred even at the lowest dose. The lowest zinc bioavailability in the prostate was found in the rats administered zinc sulfate: no significant Zn increase was seen in particular zones of the prostate. To sum up, the use of zinc gluconate is worth considering as a possible means of zinc supplementation in men.

It is thought that zinc and selenium deficiency may play a significant role in the etiology of prostate cancer. Although joint zinc and selenium supplementation is frequently applied in the prevention of prostate diseases, the bioavailability of these elements in the prostate after co-administration is still unknown. The study examines the effect of subchronic supplementation of zinc gluconate and selenium compounds (sodium selenite or selenomethionine), administered together or separately, on their bioavailability in the prostate, as well as the induction of metallothionein-like proteins (MTs) bound to zinc in the prostate and liver. Zinc concentration in the dorso-lateral lobe of the prostate was significantly elevated already after the first month of supplementation of zinc alone. In the supplementation period, the MTs level increased together with zinc concentration. In contrast, the ventral lobe of the prostate did not demonstrate significantly higher levels of zinc until after three months of supplementation, despite the MTs induction noted after one-month supplementation. Increased selenium levels in the dorsolateral lobe were observed throughout the administration and post-administration periods, regardless of the selenium compound used or whether zinc was co-administered. The results of our studies suggested for the first time that these elements should not be administered jointly in supplementation.

Polychlorinated naphthalenes (PCNs), like other persistent organic pollutants (POPs), are widespread, global environmental contaminants. These compounds still represent a great environmental problem, mostly because of the risk of secondary air pollution. They are characterized by long durability and tendency to bioaccumulate, which means that they are practically ubiquitous in all environmental media and ecosystems. The aim of this study was to investigate the distribution and excretion of hexachloronaphthalene (HxCN) in rats following a single intraperitoneal or intragastrical administration.Experiments were performed on male outbred Wistar rats with body weight of 220-240 g. They were given [(14)C]-HxCN intraperitoneally (i.p.) or intragastrically (p.o.) in a single dose of 0.3 mg (150 kBq) per rat. The distribution of radioactivity in blood and selected organs or tissues, as well as urine and faeces excretion were traced following the administration.The decline of [(14)C]-HxCN in plasma was biphasic and the calculated half-lives for phases I and II were ~6 and 350 h, respectively. Following 120 h after administration, ~51% (intragastrical) and ~34% (intraperitoneal) of the dose were excreted with faeces. Regardless of the administration route, the highest HxCN concentrations were found in liver and adipose tissue, where the compound showed high retention: the highest retention in liver was found 24 h after intragastrical (32%) and intraperitoneal (38%) administration while in adipose tissue ~30% retention was observed 120 h after HxCN administration regardless of its route.Following the calculation of the balance of total [(14)C]-HxCN excreted and stored, it was found that hexachloronaphthalene belongs to the compounds of a slow turnover rate, and in the case of repeated exposure it may accumulate in the rat body.

Objectives: N-methyl-2-pyrrolidone (NMP) belongs to solvents widely used in the petrochemical industry a well as in the production of pesticides, veterinary drugs and paint removers. NMP is easily absorbed from the respiratory tract, digestive system and through the skin. It is a compound of slight acute toxicity that also displays moderate irritating activity. The aim of this study was to assess tissue distribution and excretion following a single intraperitoneal NMP administration. Materials and Methods: Tissue distribution and excretion of NMP following administration of a single dose of 250 mg/kg body weight (350 kBq/rat) was investigated using 14 C. Blood plasma (6 rats per time point) were sampled up to 72 h after administration and determination of radioactivity. Male and female rats (4 animals per time point) were decapitated at appropriate time intervals and examined tissues were removed for determination of radioactivity. Excretion of 14 C in urine and feces were also measured. All radioactivity measurements were carried out using a Rackbetta 1209 (LKB, Sweden) liquid scintillation counter. Results: The highest 14 C activity in tissues and internal organs of female and male rats was observed 4 h after administration of the compound. The highest accumulation was detected in the muscles and fat tissue as well as in the liver and testicles. During 72 h following administration, approximately 80% of the dose was excreted in urine. Elimination of the compound in feces was far less significant: only about 5% of the dose was excreted at once. Conclusions: The results of the study indicate that there are no significant differences in 14 C-NMP tissue distribution between male and female rats; NMP absorption from the peritoneal cavity to blood is rapid, disappearance from plasma is monophase and kidneys are the main route of excretion of NMP and/or its metabolites from the rat body after administration of a dose equal to 10% of LD 50 . The ability to accumulate NMP and/or its metabolites in testes and seminal vesicles may be the reason for fertility impairment in male rats observed after repeated exposure to this compound.

Polychlorinated naphthalenes are widespread, persistent environmental pollutants. Commercial products are generally mixtures of several congeners and range from thin liquids to hard waxes of high melting point. The higher chlorinated naphthalene products are used as impregnants for condensers and capacitors and dipping encapsulating compounds in electronics. The aim of this study was to investigate the disposition of penta- and tetrachloronaphthalene in rats following a single intraperitoneal administration.Experiments were performed on male Outbred Wist rats with body weight of 200-250 g. Both compounds labeled with tritium, were given intraperitoneally in a single dose of 10 mg/kg body weight. Blood and selected tissues distribution of 3H-radioactivity as well as urine and feces excretion from 0 to 336 h were traced following the administration.After 120 h about 70% of the given dose was excreted in feces. Feces proved to be the main route of tritium excretion; only about 6% were excreted in urine within 120 h. In all the examined tissues, the highest 3H concentrations were found in the fat tissue, liver, kidneys and adrenals.Following calculations of the balance of total tritium excreted and stored, it was found out that both chloronaphthalenes belong to compounds of slow turnover rate in the rat body, and especially in the case of repeated exposure they might accumulate in the body.

Methylnaphthalenes have been used extensively as chemical intermediates in organic synthesis, as solvents for pesticides, sulphur and various aromatic compounds. A wide use of methylnaphthalenes has contributed to their emission into the environment. The aim of the study was to explain the role of glutathione in metabolism of selected dimethylnaphthalenes in rat.The experiments were conducted on male rats of the strain outbred IMP:WIST The animals were administered a single intraperitoneal dose (600 mg/kg body weight) of dimethylnaphthalenes (1,2-DMN; 1,3-DMN; 1,4-DMN) or dimethylnaphthalenes-[ring-U-3H]: (1,2-DMN-[3H]; 1,3-DMN-[3H]; 1,4-DMN-[3H]). The analysis was performed after 4, 8, 24, 48 h. The biochemical parameters were indicated: hepatic and pulmonary GSH, a-GST, SDH, GPX in blood, and adduct levels in the liver and lung.The investigations demonstrated that a single intraperitoneal administration of dimethylnaphthalenes to rats at a dose of 600 mg/kg body weight caused a substantial depletion of reduced glutathione (GSH) level both in the liver and lung. The activity of a-glutathione S-transferases in serum of experimental animals exposed to dimethylnaphthalenes increased only after 1,2-DMN administration, the compound for which in earlier investigations the largest number of sulphur-containing metabolites was found in urine. To evidence that deep GSH depletion in analyzed organs has no oxidative nature, glutathione peroxidase activity in blood was determined.Lack of changes in glutathione peroxidase and sorbitol dehydrogenase activity for all the investigated compounds suggests that significantly deep GSH depletion in liver was not of oxidative nature and did not lead to necrotic changes in produced metabolites binding with GSH.