Showing papers by "Mariana Mitewa published in 2012"

Cytostatic and cytotoxic properties of monensic acid and its biometal(II) complexes against human tumor / non-tumor cell lines

Abstract: The anticancer activity of monensic acid (MonH) and its biometal(II) complexes [M(Mon) 2 (H 2 O) 2 ] (M = Mg, Ca, Mn, Co, Ni, Zn) was evaluated against cultured human permanent cell lines established from glioblastoma multiforme (8MGBA) and cancers of the lung (A549), breast (MCF-7), uterine cervix (HeLa) and liver (HepG2). The viability and proliferation of the non-tumor human embryonic cell line Lep3 was also tested. The investigations were carried out using a thiazolyl blue tetrazolium bromide test, neutral red uptake cytotoxicity assay, crystal violet staining, colony forming method and double staining with acridin orange and propidium iodide. The results obtained reveal that the compounds applied at concentrations of 0.5-25 µg mL -1 for 24-72 h decrease the viability and proliferation of the treated cells in a time- and concentration-dependent manner. The metal(II) complexes studied (especially those of Co(II), Ni(II) and Zn(II)) have been found to express stronger cytotoxic and cytostatic activities than the non-coordinated monensic acid. The non-tumor human cell line showed strong chemosensitivity towards compounds tested comparable to that of cultured human tumor cell lines.

Cobalt-Induced Changes in the Spleen of Mice from Different Stages of Development

Abstract: Cobalt(II) accumulates in organs such as spleen, kidneys, heart, and liver. The aim of the present study was to investigate the effects of cobalt ethylenediamine tetraacetic acid (Co-EDTA) on spleen of developing mice. Pregnant BALB/c mice in late gestation were subjected to Co-EDTA treatment at daily doses of 75 or 125 mg/kg in drinking water, which continued until d 90 of the newborn pups. The newborn pups were sacrificed on d 18, 25, 30, 45, 60, and 90, which correspond to different stages of development. Spleens were excised, weighed, and processed for histological analysis. Spleen index (SI) was calculated as a ratio of spleen weight to body weight. Cobalt(II) bioaccumulation in spleen was determined using flame atomic absorption spectrometry (FAAS). Preliminary results showed that chronic treatment of mice with low- or high-dose Co-EDTA disturbed extramedullary hematopoiesis in the spleen. The number of megakaryocytes was reduced compared to controls. SI was also reduced in d 18 mice treated with low- or high-dose Co-EDTA. However, exposure to 75 mg/kg led to an increase of SI in all other experimental groups. FAAS analysis revealed significant cobalt(II) accumulation in spleen of treated mice. The Co(II) levels in spleens of d 18 mice were highest compared to other experimental groups, indicating that at this period mice are more sensitive to treatment. Exposure to cobalt-EDTA resulted in accumulation of Co(II) in spleen, altered SI, and hematopoiesis. Immature mice appear to be more sensitive to chronic treatment than adults.

Cobalt(II)-Induced Changes in Hemoglobin Content and Iron Concentration in Mice from Different Age Groups

Abstract: Cobalt (Co) and its compounds are shown to improve hematological parameters. Long-term treatment with Co(II) increased hemoglobin content in a dose- and time-dependent manner in mature mice (day 45 to day 90) while it was reduced in immature mice (day 18 to day 30). Higher Hb was measured in samples treated with CoCl2 compared to those treated with Co-EDTA. Plasma Fe concentration was significantly higher in samples treated with Co-EDTA compared to those exposed to CoCl2. Lower concentrations were measured only in mature animals. Co(II) concentration increased but not in a dose-dependent manner. In general more Co(II) was measured in samples treated with CoCl2 possibly due to the stability of the complex Co-EDTA. Surprisingly, mature mice had less Co(II) in their plasma compared to day 18 mice. Strong correlation between plasma Co(II) and iron concentration was found in samples of mice treated with Co-EDTA. Co(II) concentration showed inverse correlation with hemoglobin in mice treated with low do...

Structure and properties of a series of 2-cinnamoyl-1,3-indandiones and their metal complexes

Abstract: A series of seven 2-cinnamoyl-1,3-indandiones and their metal(II) complexes were synthesized and characterized by means of spectroscopic (IR, NMR, electron absorption and emission spectroscopy) and/or single-crystal X-ray diffraction methods. The optical spectra of the organic compounds show very strong absorption in the visible region and weak fluorescence with moderate to strong Stokes shift. The effect of concentration, water addition and metal ion complexation on the optical properties was also studied. In search of potential practical application, the complexation of 2-cinnamoyl-1,3-indandiones with metal(II) ions was investigated. A series of non-charged complexes with Cu(II), Cd(II), Zn(II), Co(II) and Ni(II) was isolated and analyzed by elemental analyses and IR. Most of the complexes show presence of water molecules, most probably coordinated to the metal ion, thus forming octahedral geometry. For the paramagnetic Cu(II) complexes a distorted, flattened tetrahedral structure is proposed, basing on the EPR data. The optical properties of the metal complexes, however, do not differ appreciably from those of the free ligands.

Effect of cobalt-edta on iron content in spleen and liver of immature mice

Abstract: Cobalt (Co) is an essential trace element and its accumulation affects the concentrations of other elements. Co(II) is shown to compete with iron (Fe) for the transferrin receptor and to form a stable complex with hemoglobin thus affecting hematopoiesis. There are lack of data regarding the effect of chronic exposure to Co compounds and Fe content in spleen and liver of mice. The study investigates the effect of long-term treatment with cobalt-EDTA (Co-EDTA) on iron content in the spleen and liver of immature mice. Pregnant ICR mice were subjected to chronic treatment with daily dose of 75 mg/kg Co-EDTA which continued until d25 of the newborn pups. Results show accumulation of Co(II) in the organs of treated mice compared to age-matched controls. Fe content in the spleen and liver was affected as well. Significantly increased concentrations of Fe ions were measured in the livers of treated mice. The changes could explain impaired hematopoiesis and immune responses of exposed to Co(II) immature mice.

Acute toxicity of vipoxin and its components: is the acidic component an "inhibitor" of PLA2 toxicity?

Abstract: Vipoxin is a heterodimeric neurotoxin isolated from the venom of the Bulgarian long-nosed viper Vipera ammodytes meridionalis. Vipoxin represents a noncovalent association of two subunits – a basic and toxic phospholipase A2 enzyme, and an acidic non-enzymatic component (vipoxin's acidic component). It was postulated that the phospholipase A2 subunit was more toxic than the whole vipoxin complex and the function of the acidic component was to reduce the enzymatic and toxic activities of the basic phospholipase A2. In the present study, we report new data on the acute toxicity (LD50) of vipoxin and its individual separated components. Vipoxin LD50 (mice, i.p. and i.v.) values were found to be 0.7–1.2 mg/kg b.w. (i.p.) and 0.9–1.3 mg/kg b.w. (i.v.). The established LD50 values for the separated pure phospholipase A2 subunit are higher – 10.0–13.0 mg/kg b.w (i.p.) and 2.2–3.0 mg/kg b.w. (i.v.), i.e. the individual phospholipase A2 subunit displays less toxic activity than vipoxin, contrary to the data published in the literature. The reconstituted vipoxin complex (obtained after preliminary incubation of pure separated phospholipase A2 and acidic component showed enzyme activity and toxicity comparable to that of the native vipoxin complex. Addition of acidic component to the phospholipase A2 subunit showed a positive effect on the enzymatic activity, reaching maximal enzyme reaction rate of acidic component to phospholipase A2 molar ratio of 0.8:1 on using 4-nitro-3-octanoyloxy-benzoic acid as substrate. For the first time we showed that the acidic subunit was absolutely required for the toxic activity of vipoxin. Based on the obtained results, we assume that the function of the acidic component is to stabilize the neurotoxin's quaternary structure, required for its toxic and enzymatic activities, similarly to the role of the acidic component of crotoxin.

Synthesis, Spectral Properties, Antibacterial and Antitumor Activity of Salinomycin Complexes with the Transition Metal Ions Co(II), Ni(II), Cu(II) and Zn(II)

Abstract: SalNa (sodium salinomycin) reacts with divalent transition metal ions of Co(II), Ni(II), Cu(II) and Zn(II) to produce novel compounds characterized by various spectroscopic methods. The interaction of metal (II) ions with SalNa results in the formation of mononuclear complexes of a general composition of (M(Sal)2·(H2O)2) nH2O (n = 0 or 2) where the divalent cations replace Na + ions from the cavity of initial compound. The new compounds (disalinomycinates) possess an enhanced antibacterial activity against Gram-positive microorganisms as compared to both SalNa and SalH (salinomycinic acid), respectively. The metal (II) complexes manifest strong concentration dependent cytotoxic effect in experiments using human leukemia cell lines. The complexes of Co(II) and Cu(II) proved to exert superior activity as compared to the Ni(II) and Zn(II) analogues and are much more cytotoxic than SalNa and SalH. Further studies should be conducted to determine the therapeutic indexes of the new compounds.

Effect of Co-EDTA on hematological parameters in immature mice

Abstract: As inorganic and complex compounds cobalt is used as nutritional supplement, preservative, in drinks, cosmetics, as therapeutic agent for treating different diseases. The aim of the present study is to investigate the effect of Co-EDTA on the hematological parameters of immature mice. Pregnant mice in late gestation were subjected to Co-EDTA treatment at daily doses of 75 mg/kg and the exposure continued until days 18 and 25 of the newborn pups. The compound was obtained from drinking water. Hematological parameters and serum iron (Fe) content were measured. Preliminary results show reduced red blood cell count (RBC), hemoglobin content (Hb), hematocrit (Hct) and mean cell volume (MCV) and increased MCH and MCHC in treated mice. Serum Fe was elevated in d18 mice and significantly reduced in d25 animals compared to agematched controls. Fe content was in good correlation with RBC, Hb, Hct, MCV and showed strong inverse relation with MCH and MCHC in d18 mice which corresponds to the increased values of the latter parameters in the treated group. Results indicate that treatment of immature mice with Co-EDTA induces significant hematological changes which probably alter their hemorheological properties as well.