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.

Health risk to medical personnel of surgical smoke produced during laparoscopic surgery.

OBJECTIVES: During laparoscopic cholecystectomy, the removal of the gall bladder, pyrolysis occurs in the peritoneal cavity. Chemical substances which are formed during this process escape into the operating room through trocars in the form of surgical smoke. The aim of this study was to identify and quantitatively measure a number of selected chemical substances found in surgical smoke and to assess the risk they carry to medical personnel. MATERIAL AND METHODS: The study was performed at the Maria Sklodowska-Curie Memorial Provincial Specialist Hospital in Zgierz between 2011 and 2013. Air samples were collected in the operating room during laparoscopic cholecystectomy. RESULTS: A complete qualitative and quantitative analysis of the air samples showed a number of chemical substances present, such as aldehydes, benzene, toluene, ethylbenzene, xylene, ozone, dioxins and others. CONCLUSIONS: The concentrations of these substances were much lower than the hygienic standards allowed by the European Union Maximum Acceptable Concentration (MAC). The calculated risk of developing cancer as a result of exposure to surgical smoke during laparoscopic cholecystectomy is negligible. Yet it should be kept in mind that repeated exposure to a cocktail of these substances increases the possibility of developing adverse effects. Many of these compounds are toxic, and may possibly be carcinogenic, mutagenic or genotoxic. Therefore, it is necessary to remove surgical smoke from the operating room in order to protect medical personnel.

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.

Chemical composition of surgical smoke formed in the abdominal cavity during laparoscopic cholecystectomy--assessment of the risk to the patient.

OBJECTIVES: The aim of this study was to assess the exposure of patients to organic substances produced and identified in surgical smoke formed in the abdominal cavity during laparoscopic cholecystectomy. MATERIAL AND METHODS: Identification of these substances in surgical smoke was performed by the use of gas chromatography-mass spectrometry (GC-MS) with selective ion monitoring (SIM). The selected biomarkers of exposure to surgical smoke included benzene, toluene, ethylbenzene and xylene. Their concentrations in the urine samples collected from each patient before and after the surgery were determined by SPME-GC/MS. RESULTS: Qualitative analysis of the smoke produced during laparoscopic procedures revealed the presence of a wide variety of potentially toxic chemicals such as benzene, toluene, xylene, dioxins and other substances. The average concentrations of benzene and toluene in the urine of the patients who underwent laparoscopic cholecystectomy, in contrast to the other determined compounds, were significantly higher after the surgery than before it, which indicates that they were absorbed. CONCLUSIONS: The source of the compounds produced in the abdominal cavity during the surgery is tissue pyrolysis in the presence of carbon dioxide atmosphere. All patients undergoing laparoscopic procedures are at risk of absorbing and excreting smoke by-products. Exposure of the patient to emerging chemical compounds is usually a one-time and short-term incident, yet concentrations of benzene and toluene found in the urine were significantly higher after the surgery than before it.

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 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.

The effect of cadmium on steroid hormones and their receptors in women with uterine myomas.

Cadmium (Cd) is one of the environmental metalloestrogens, and its role in uterine tissues has not yet been fully elucidated. The aim of the study was to investigate estrogenic properties of Cd in uterine tissues by analyzing the expression of estrogen receptor (ER) and progesterone receptor (PR) as well as estrogen and progesterone levels in serum and Cd concentrations in blood and tissues. The samples of tissues (leiomyoma and surrounding myometrium) collected intrasurgically and blood samples drawn from 53 women (age 39 to 52 years) with uterine myomas were thoroughly analyzed. In the study group, blood Cd concentration ranged from 0.33 to 3.5 µg/L. Cd concentration in leiomyoma tissues was twice as low [corrected] as that in surrounding myometrium (0.047 and 0.075 µg Cd/g [corrected] wet tissue, respectively), albeit the difference was not statistically significant. Cd concentrations in blood significantly correlated with Cd concentrations in tissues (leiomyoma and surrounding myometrium). The measurement of ER expression showed no difference between leiomyoma tissues and surrounding myometrium. The statistical analysis showed a significant correlation between ER expression and Cd concentration in both tissues under study. An additional statistical analysis (path analysis) demonstrated the correlation of uterine tissue levels of Cd and ER expression. However, there was no association between ER expression in both tissues and E(2) level in serum. Our results suggest a metalloestrogenic effect of Cd by way of ER stimulation in the uterus.

Prenatal developmental toxicity of polychlorinated naphthalenes (PCNs) in the rat.

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.

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.

New inhibitors of protein kinase CK2, analogues of benzimidazole and benzotriazole.

Derivatives of 4,5,6,7-tetrabromobenzotriazole (TBBt) and 4,5,6,7-tetrabromobenzimidazole (TBBi) with IC50 in the low micromolar range and with high selectivity belong to the most promising inhibitors of protein kinase CK2 (casein kinase 2). Treatment of various cell lines with TBBt, TBBi or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT) affected cell viability with simultaneous induction of apoptosis. The inhibitory activity of newly synthesized hydroxyalkyl derivatives of TBBi and TBBt depends on the length of the alkyl chain. The hydroxypropyl substituted derivatives show higher or similar inhibitory activity than the parent compounds when tested with human protein kinase CK2. To test the distribution of this class of compounds in mammals, [14C] TBBi was synthesized.

Tissue distribution and elimination of selected chlorinated naphthalenes.

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

[Toxic effect of dust and fumes of aluminium and its compounds on workers' respiratory tract]. / Toksyczne oddzialywanie pylów i dymów glinu oraz jego zwiazków na drogi oddechowe pracowników.

Based on the literature review, the authors discuss problems concerning differentiated exposure of workers to dust and fumes of aluminum and its compounds and describe the observed toxic effect on the respiratory tract. Long- term occupational exposure to the above factors leads to changes in lungs of the pneumoconiotic nature. Other disorders presented in the literature include: pulmonary fibrosis, pulmonary alveolitis and alveolar proteinosis, asthma, chronic bronchitis, and chronic pneumonia. The respiratory effect depends to some extent on the form of aluminum or the stage of processing in which exposure occurs. Numerous studies of workers occupationally exposed to aluminum dust and fumes have demonstrated the increase in the incidence of pulmonary fibrosis, depending on the air concentration of respirable fraction of dust.

Maternal-fetal distribution and prenatal toxicity of 2,2,4-trimethyl-1,2-dihydroquinoline in the rat.

BACKGROUND: Polnoks R (poly-2,2,4-trimethyl-1,2-dihydroquinoline) is used as an antioxidant in elastomer processing. It is an embryotoxic and fetotoxic agent. This chemical given per os to female rats induces also teratogenic effect but only at doses toxic to the mother. The aim of the study was to evaluate prenatal development and tissue distribution in rats exposed to 2,2,4-trimethyl-1,2-dihydroquinoline (TMDHQ), a monomer of Polnoks R. METHODS: Females were exposed orally to unlabeled TMDHQ during organogenesis at doses 50-400 mg/kg to asses prenatal toxicity and to radiolabeled 14C monomer at a dose 210 mg/kg to evaluate tissues distribution. RESULTS: TMDHQ administered to pregnant females per os at doses 100 mg/kg and higher produced teratogenic effect (cleft palate, wavy ribs, kyphoscoliosis, exencephaly, external hydrocephalus, hydronephrosis, and renal hypoplasia). Peak 14C-radioactivity was found in mothers' plasma about 10 hr after administration of this compound at dose 210 mg/kg. The accretion of 14C proceeded with a kinetic constant of 0.35 hr(-1) and a half-life of 53.3 hr. Kidneys are the main organs of monomer excretion. The highest concentration of 14C in maternal tissues 24 hr after oral dosing was found in adipose tissue, sciatic nerve, muscles, kidneys, and liver. Radiocarbon retention in fetuses was the highest in kidneys at all time points after dosing. CONCLUSIONS: This study has demonstrated that transplacental exposure to Polnoks R monomer is teratogenic in rats. 14C retention in placenta, amniotic fluid, and fetal tissues indicates that this compound or its metabolites penetrate into placenta to the fetus.

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.

Tissue distribution, excretion and metabolism of o-anisidine in rats.

OBJECTIVES: The principal commercial use of o-anisidine is believed to be as an intermediate in the manufacture of dyes. It has also been reported to be an intermediate in the manufacture of synthetic guaiacol and its derivatives. o-Anisidine is an urinary bladder carcinogen in mice and rats. The aim of the study was to investigate the kinetics of body distribution, excretion and biotransformation of o-anisidine in rats following a single, intraperitoneal administration. MATERIALS AND METHODS: The tissue distribution and excretion of o-anisidine following i.p. administration of a single dose of 10 mg/kg was investigated using radiotracer [3H]. Metabolism of o-anisidine was investigated in the rats following i.p. administration of a single dose of 50 mg/kg using GC/MS technique. RESULTS: After 72 h, about 72% of the given dose was excreted in urine. As indicated, urine proved to be the main route of tritium excretion. In all examined tissues, the highest concentrations of tritium were found 12 h after injection and the highest accumulation was detected in the liver, kidneys and in the muscle tissue. In urine, the following substances were identified and quantified by GC peak areas: N-acetyl-2-methoxyaniline and N-acetyl-4-hydroxy-2-methoxyaniline. CONCLUSIONS: Prolonged tritium retention observed in the majority of tissues indicated that o-anisidine, especially in the case of repeated exposure, might accumulate in the body. The metabolism encompasses amine group acetylation and ring oxidation.