Assessment of lead exposure in indoor shooters in central Poland.

A steady increase in shooting practices is observed worldwide. Potential lead exposure at shooting ranges poses a risk to their employees and users, which is not widely reported outside of the USA, especially in Poland. Exposure to lead results from the use of bullets containing lead and the main route of exposure to this metal at shooting ranges is inhalation, i.e., during shooting or cleaning. The aim of this study was to assess lead exposure of employees and users in selected indoor shooting ranges in central Poland. Airborne lead concentrations at all locations in the shooting ranges were above Polish occupational exposure limit (OEL, 0.05 mg m-3). Elevated blood and urine lead levels, and decreased 4-aminolevulinic acid dehydratase activity (ALA-D) were found in subjects participating in shooting even for only a few (< 10) hours per week. Lead exposure at shooting ranges in central Poland, as indicated by elevated blood lead levels and decreased ALA-D activity, could represent an elevated risk for adverse health effects. Thus, information on the possible health consequences of lead exposure should be provided at these sites, and biomonitoring appears to be reasonable for regular workers and shooters.

Age-Related Changes in Zinc, Copper and Selenium Levels in the Human Prostate.

Pathophysiological changes in the prostate gland-benign prostatic hyperplasia (BPH) and prostatic adenocarcinoma (PCa)-are closely related to the age of men. In the prostate gland, zinc is of particular importance for its proper functioning, especially with regard to the effects of hormonal disorders. The aim of this study was to evaluate zinc, copper and selenium concentrations in different parts of the prostate gland in relation to age and the nature of pathological changes. Zinc and copper were determined by the AAS method and selenium by the spectrofluorometric method. The concentration of zinc in the central part of the prostate increases with age, and in patients over 36 years it is twice as high as in the peripheral part, where no increase in the level of this element was observed with the age of patients. The above data confirm a possible influence of zinc on the formation of PCa (located mostly in the peripheral part of the prostate, with low levels of zinc) and BPH in the central part where the levels of this element are the highest. The results apparently confirm the disturbed homeostasis of zinc and other essential elements in the etiology of BPH and PCa.

The Effect of Zinc, Selenium, and Their Combined Supplementation on Androgen Receptor Protein Expression in the Prostate Lobes and Serum Steroid Hormone Concentrations of Wistar Rats.

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.

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 effect of repeated cadmium oral exposure on the level of sex hormones, estrous cyclicity, and endometrium morphometry in female rats.

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.

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.

Optimization of ultra-performance liquid chromatography (UPLC) with fluorescence detector (FLD) method for the quantitative determination of selected neurotransmitters in rat brain.

BACKGROUND: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The Effect of Zinc and Selenium Supplementation Mode on Their Bioavailability in the Rat Prostate. Should Administration Be Joint or Separate?

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.

Concentrations of cadmium and selected essential elements in malignant large intestine tissue.

INTRODUCTION: Colorectal cancer is one of the most common cancers worldwide. Incidence rates of large intestine cancer indicate a role of environmental and occupational factors. The role of essential elements and their interaction with toxic metals can contribute to the explanation of a complex mechanism by which large intestine cancer develops. Bearing this in mind, determining the levels of essential and toxic elements in tissues (organs), as well as in body fluids, seems to shed light on their role in the mode of action in malignant disease. AIM: Determination of the levels of cadmium, zinc, copper, selenium, calcium, magnesium, and iron in large intestine malignant tissue. MATERIAL AND METHODS: Two intraoperative intestine sections were investigated: one from the malignant tissue and the other one from the normal tissue, collected from each person with diagnosed large intestine cancer. Cadmium, zinc, copper, calcium, magnesium, and iron levels were determined with atomic absorption spectrometry, and selenium levels by spectrofluorimetric method. RESULTS: The levels of copper, selenium, and magnesium were higher in the malignant than in normal tissues. In addition, the zinc/copper and calcium/magnesium relationship was altered in malignant tissue, where correlations were lower compared to non-malignant tissue. CONCLUSIONS: The results seems to demonstrate disturbed homeostasis of some essential elements. However, it is hard to confirm their involvement in the aetiology of colorectal cancer.

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.

Involvement of oxidative stress in the mechanism of cadmium-induced toxicity on rat uterus.

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 bioavailability of different zinc compounds used as human dietary supplements in rat prostate: a comparative study.

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.

The effect of cadmium on the coagulation and fibrinolytic system in women with uterine endometrial cancer and myoma.

OBJECTIVES: Cadmium (Cd) is a persistent and widespread environmental pollutant, which may constitute a potential risk factor for hormone-dependent tumors such as endometrial cancer. The vascular endothelium is an important target of cadmium toxicity, which may interfere with the coagulation cascade and fibrinolytic system. The aim of this research was to investigate whether in female patients with uterine endometrial cancer or myoma in comparison to healthy women, the concentration of cadmium in blood affects the process of coagulation and fibrinolysis. MATERIALS AND METHODS: The study group comprised 91 women: 35 healthy (A-control), 39 with uterine myoma (B) and 17 with endometrial cancer (C), in which blood cadmium concentrations (BCd), coagulation and selected fibrinolysis parameters in plasma were assayed. RESULTS: In the women with myoma and especially in those with endometrial cancer disturbances in coagulation and fibrinolysis were detected when compared to the healthy women. In the group of women with endometrial cancer significant changes in prothrombin index, levels of fibrinogen, fibrin D-dimer and t-PA were observed. Whereas, in the patients with myoma significant changes in prothrombin time, index of vWillebrand Factor and fibrin D-dimer level were noted. Mean BCd concentrations in subsequent groups were as follows: B - 0.91±0.81; C - 0.78±0.45 µg Cd/l and did not differ significantly in comparison with the control group (0.86±0.35 µg Cd/l). However, in each study group smokers had approximately twice as high BCd as non-smokers. Studies also showed significant associations between BCd and fibrinogen level and thrombin time among the women with myoma and endometrial cancer, as well as in healthy women. Moreover, thrombin time significantly correlated with fibrinogen level in the women studied. CONCLUSIONS: In the patients with myoma and especially in these with endometrial cancer disturbances in coagulation and fibrinolysis parameters leading to hypercoagulability were detected. Exposure to cadmium can be one of the factors inducing these changes.

The effect of exposure route on the distribution and excretion of hexachloronaphthalene in rats.

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The correlation between zinc and insulin-like growth factor 1 (IGF-1), its binding protein (IGFBP-3) and prostate-specific antigen (PSA) in prostate cancer.

BACKGROUND: The objective of the present study is to explore the association between zinc concentrations and insulin-like growth factor 1 (IGF-1), its binding protein (IGFBP-3) and total prostate-specific antigen (tPSA) levels in the serum of patients with prostate cancer (PCa) and prostate intraepithelial neoplasia (PIN), a pre-cancer state matched for age. METHODS: The study was carried out in a group of 229 patients who had transurethral prostate biopsy performed. The patients were divided into three groups: control group (BPH), PIN group or PCa group. The patients had plasma zinc concentration determined by atomic absorption spectrometry; IGF-1, IGFBP-3 analyzed using the chemiluminescence method and tPSA detected in serum with DELFIA assay. RESULTS: The studies revealed that, in PCa and PIN patients aged under 65 years, mean zinc concentrations were significantly lower compared with the control group. IGF-1 level significantly increased with decreasing level of zinc in plasma, hence a significantly decreased Zn/IGF-1 ratio. The mean tPSA concentration was significantly increased only in PCa patients of both age groups, whereas the Zn/tPSA ratio significantly decreased with increasing severity of neoplastic lesions, particularly in patients aged under 65 years. Statistical significance was noted for IGF-1:tPSA and IGFBP-3:tPSA ratios, being almost two-fold lower in the PCa patients than in the control group. CONCLUSIONS: A significantly lowered Zn/tPSA ratio appears to be a sensitive marker of neoplastic lesions, PCa and PIN, regardless of age. In men under 65 years, the Zn/IGF-1 ratio was reduced, depending on the stage of neoplastic lesions (PIN>PCa). These finding can be useful in early diagnosis of prostate cancer.

Disturbed homeostasis of zinc and other essential elements in the prostate gland dependent on the character of pathological lesions.

Pathophysiological changes in the prostate take the form of benign prostate hyperplasia (BPH) and prostate adenocarcinoma (PCa). In prostate, zinc is particularly important to its normal functioning, especially in terms of the consequences of hormone disturbance. The aim of this study was to assess the levels of Zn, Cu, Ca, Mg, and Se in the prostate dependent on the character of patological changes. Zinc, copper, magnesium and calcium were determined by AAS and selenium with spectrofluorometric method. Zn levels in BPH patients were over twofold higher than in controls. On the other hand, in the patients with PCa, the levels of Zn were found almost three times lower than in BPH patients and by almost 50% lower than in controls. In this study, significant changes in the levels of other essential elements were observed. The results apparently confirm the disturbed homeostasis of zinc and other essential elements in the etiology of BPH and PCa.

Subacute toxicity of polychlorinated naphthalenes and their effect on cytochrome P-450.

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.

The role of glutathione in metabolism of selected dimethylnaphthalenes in rat.

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.