Anna Kilanowicz

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.

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.

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

Abstract 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.

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.

Toxicity of hexachloronaphthalene (HxCN) and induction of CYP 1A in rats

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 (250mg/kg) and repeated (1 and 10mg/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 1mg HxCN/kgb.w.

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.

Exposure to polychlorinated naphthalenes affects GABA-metabolizing enzymes in rat brain.

There is substantial evidence that polychlorinated naphthalenes (PCNs) are widespread global environmental pollutants, which accumulate in biota. The aim of our study was to characterize the effect of prolonged PCNs exposure on γ-aminobutyric acid (GABA) metabolism in rat brain regions with a high amount of GABAergic neurons (cerebellum, brain stem and basal ganglia). PCNs mixture was administered intragastrically for 7, 14 and 21 days in a dose 10mg/kg of body weight daily, and next the activity of glutamate decarboxylase (GAD), GABA-aminotransferase (GABA-T), succinic semialdehyde dehydrogenase (SDH) and succinate dehydrogenase (SSA-DH) was assayed. PCNs administration altered all examined activities in the selected brain areas, except GAD in basal ganglia. The results suggest the correlation between PCNs action and disturbance in GABA metabolism in rat brain. Moreover, the chronic PCNs intoxication increased SDH-mediated activation of TCA cycle, and it may be a kind of protective mechanism developed in nervous tissue in response to administration of toxic compounds.

Disposition and metabolism of 1,6-dimethylnaphthalene in rats

The distribution, excretion and metabolism of 1,6-dimethylnaphthalene following i.p. administration of a single dose of 20 mg/kg to rats, was investigated using radiotracer [3H] and a gas chromatography-mass spectrometry technique (GC-MS). After 72 h, about 94% of the given dose was excreted in urine and feces. In organs and tissues, the highest concentration during the first hours after administration was detected in fat, liver, spleen and kidneys. Then gradual decline of tritium was noticed in all examined tissues. In urine, the following substances were identified and quantified by GC peak areas: unchanged 1,6-dimethylnaphthalene, 1-methyl-hydroxynaphthalenes, 1-hydroxymethyl-6-methylnaphthalene, 1,6-dimethyl-thionaphthalene, 6-methyl-1-naphthoic aldehyde, 6-methyl-1-naphthoic acid, 1,6-dimethyl-thionaphthalene and 1,6-dimethyl-methylthionaphthalene.

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

ObjectivesCadmium (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 MethodsThe 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.ResultsIn 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.ConclusionsIn 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.