Marzenna Nasiadek

Tissue levels of cadmium and trace elements in patients with myoma and uterine cancer

The aim of this study was to investigate the cadmium (Cd), copper (Cu), zinc (Zn), iron (Fe), magnesium (Mg) and calcium (Ca) concentrations in uterine cancer and uterine myoma. Tissue levels of six elements in 15 uterine cancers and 28 uterine myomas were measured by atomic absorption spectrometry. The samples were collected from women aged 32-79 (uterine myomas, uterine cancer and non-lesion uterine tissues from the same women). The results showed that the tissue Cd concentration was significantly lower in myoma than in non-lesion tissue. In uterine cancer, however, it was statistically significant, but only slightly lower than controls (the non-lesion uterine tissue). In the investigated tissues, the correlation between Cd concentration and age was found, but no effect of menopausal status or smoking habits on Cd level was detected. In uterine cancer tissue, a significant increase in Ca concentration and an insignificant increase in Mg level was observed when compared to normal uterine tissue. In uterine myoma, a significant increase of Mg and Mg/Ca ratio, as well as a decrease in Fe concentration were found. Statistical analysis showed no correlation between smoking habits, age, menopausal status and concentration of Cu, Zn, Fe, Mg and Ca trace metals in myoma or cancer tissue.

The trace elements in response to lithium intoxication in renal failure.

The polyuric syndrome that develops as a consequence of chronic administration of lithium salts is most frequent and often causes complication in the treatment of manic depressive disease with the administration of drugs. It is known that kidneys play an essential role in systematic depositing of toxic metals. The purpose of this study was not only the determination of dose-dependent lithium concentration in serum and urine but also an estimation of sensitive biochemical indicators of nephrotoxicity detectable at an early stage after the administration of lithium carbonate to rats. Animals were given orally lithium salt to female Wistar rats at the dose of 10 and 20mg Li/kg daily during 5 weeks. In the urine diuresis protein concentration, copper, zinc, lithium and N-acetyl-beta-glucoaminidase (NAG) activity were determined. In the serum also lithium, copper and zinc were analyzed. The results of the experiments indicate that the changes in urinary concentrations of essential copper, proteins, NAG activity and diuresis were observed when the concentration of lithium was ca. 9.79+/-1.68 mmol Li/L and in serum it corresponded to 0.3+/-0.06 mmol Li/L. These values corresponded to total doses of 150 mg Li/kg body weight administered to rats. In summary the increase of copper concentration, diuresis and urinary concentrations of protein and the NAG activity may be interpreted as a general metabolic response of kidneys induced by lithium detectable as an earlier indicator of nephrotoxicity. Therefore, regular determinations of lithium concentrations in serum of patients are important tools in the prevention of intoxication.

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.

Disturbances of morphological parameters in blood of rats orally exposed to aluminum chloride

The aim of this work was to assess changes of morphological parameters in the blood of rats after oral (po) administration of aluminum (Al), in relation to the time and the administered dose. The experiment was performed on female Wistar rats. The animals were administered aluminum chloride (100 mg Al/kg) daily for 21 d. Morphological assays: red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), iron serum concentration (Fe), MCH, MCHC, absolute corrected reticulocyte count (ACRC), white blood cells (WBC), and platelet count (PLT) were estimated on d 3, 7, 14, and 21, both in the control group and in intoxicated rats. After wk 1 of aluminum administration we observed a decrease of RBC, HCT, HGB and serum iron concentration in the blood of rats. The increase of the platelet count was observed earlier than changes in other parameters. Investigation has proved that the exposure of rats to aluminum administered orally results in normocytic anemia.

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.

Tissue distribution and urinary excretion of essential elements in rats orally exposed to aluminum chloride

The purpose of this study was to determine disorders in the metabolism of the essential elements (Ca, Fe, Cu, and Zn) in some tissues of rats, as well as to detect the dynamics of urinary excretion of these metals after oral administration of 20 mgAl/kg every day for 8 wk. The elements were determined in brain, kidneys, blood, and urine of the animals in 1st, 2nd, 3rd, 4th, and 8th wk after the exposure to AlCl3. After the 1st wk of aluminium administration, we observed increase of Ca and a decrease of Fe in blood. In brain Ca, Fe, and Cu concentrations were significantly higher in Al-treated rats than in controls after 8-wk exposure. The concentration changes of the essential metals in the tissue were accompanied by increase of the Ca, Fe, and Zn urinary excretion. We assume that the increase in urinary excretion of Ca and the decrease of Fe in the blood may be sensitive indicators of oral aluminium administration.

COMBINED EFFECT OF TIN AND LEAD ON HEME BIOSYNTHESIS IN RATS

The aim of the present study was to investigate the combined effect of tin (SnCl2) and lead Pb(CH3COO)2 on activity of heme biosynthesis enzymes [delta-aminolevulinic acid synthetase (ALA-S) and heme oxygenase] in liver and kidneys, as well as iron (Fe) and copper (Cu) concentration in serum of rats. The experiment was performed on female rats which received 2 mg Sn/kg and 3.5 mg Pb/kg separately and jointly intraperitoneally (ip) for 5 days and per os (po) at single dose (100 mg Sn/kg and 17.5 mg Pb/kg). Lead induced ALA-S in liver and kidney both after ip and po administration; tin, however, induced ALA-S only after ip administration in liver of rats. The activity of heme oxygenase was induced after Sn po and ip administration in liver and kidneys and Pb administration (ip) in kidneys. Sn and Pb administered jointly caused a significant increase of Cu (ip), whereas Sn (po) decreased this metal level in serum of rats. Kidneys proved to be the organ in which the highest degree of examined enzyme induction took place. Pb is responsible for ALA-S, whereas Sn is responsible for induction of heme oxygenase activity in this organ, especially after per os administration. No additive effect on ALA-S and heme oxygenase activities of Pb and Sn combined was noticed.

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.

Erratum to: The Effect of Cadmium on Steroid Hormones and Their Receptors in Women with Uterine Myomas

Erratum to: Arch Environ Contam Toxicol (2011)60:734–741DOI 10.1007/s00244-010-9580-8The original version of this article unfortunately containeda mistake. In the Abstract section, the sentence ‘‘Cd con-centration in leiomyoma tissues was twice as high as that insurrounding myometrium (0.48 and 0.75 lg Cd/g wet tis-sue, respectively), albeit the difference was not statisticallysignificant.’’ should read as follows: Cd concentration inleiomyoma tissues was twice as low as that in surroundingmyometrium (0.047 and 0.075 lg Cd/g wet tissue,respectively), albeit the difference was not statisticallysignificant.

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.