Showing papers by "Mariana Mitewa published in 2013"

Effect of Some Divalent Metal Ions on Enzymatic Activity of Secreted Phospholipase A2 (sPLA2) Isolated from Bulgarian Vipera Ammodytes Meridionalis

Abstract: effect of Ca 2+ and some divalent metal ions related to it (Mg, Sr, Ba, Cd) on the hydrolysis of natural and artificial substrates catalyzed by vipoxin secreted phospholipase A 2 subunit (sPLA 2 ) was evaluated. The results showed that the hydrolysis of natural glycerophospholipids proceeds at a highest rate when the enzyme is activated by calcium ions. The catalytic activity of sPLA 2 decreased in the presence of other metal ions possibly due to their lower coordination ability to the head group of lipids. Oppositely, the hydrolysis of artificial substrates was facilitated by metal ions with ionic radii larger than Ca 2+ , such as Sr 2+ and Ba 2+ , suggesting that not only the interaction with metal cations, but also the origin of the head group should be considered. The fluorescence assay revealed that conformational changes occur during the coordination of metal ions into the catalytic site of sPLA 2 prior to subsequent hydrolysis. It could be concluded that the rate-limiting step in the catalytic cycle (e.g. the chemical interaction) is not completely adequate to evaluate all factors affecting the hydrolytic activity of vipoxin sPLA 2 .

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.

Effects of Cadmium and Monensin on Spleen of Mice, Subjected to Subacute Cadmium Intoxication

Abstract: This study investigated the effects of cadmium (Cd) and monensin on spleen function in mice, subjected to subacute Cd-intoxication. Adult male ICR mice were divided into three groups (n = 6 per group) as follows: control group (received distilled water and food ad libitum); Cd-treated (20 mg/kg/b.w./day Cd(II) acetate for the first 2 weeks of the experimental protocol); monensin-treated mice (20 mg/kg/day Cd(II) acetate for the first 2 weeks followed by treatment with 16 mg/kg b.w./day monensin from days 15 to 28. On day 29, mice were sacrificed under light ether anesthesia. Exposure to Cd induced an increase in spleen index (SI). The treatment of cd-intoxicated mice with monensin significantly reduced SI compared to Cd alone. The data from the atomic absorbption analysis of spleen revealed a significant Cd accumulation in Cd-treated mice compared to controls, accompanied by a significant depletion of Fe concentration up to 30%. The treatment of the Cd-administered mice with monensin resulted in a signifi...

On the effect of chelating agents and antioxidants on cadmium-induced organ toxicity. An overview

Abstract: Cadmium (Cd) has been classified as a human carcinogen. The World Health Organization (WHO) reported that the concentration of Cd in the environment has rapidly increased in the last few years. In many epidemiological studies, the correlation between environmental exposure of humans to Cd and diseases such as stroke, ischemia, renal and hepatic dysfunction, anemia, osteoporosis and diabetes has been discussed. For the treatment of heavy metal intoxications a therapy with chelating agents has been applied. A chelating agent is a compound that binds the toxic metal ion thus promoting its excretion by the living organisms. Recently, it has been found that Cd-induced toxicity is a result of formation of reactive oxygen species (ROS). These results increased the interest towards the antioxidants as possible agents for the treatment of Cd-induced organ toxicity. Herein, we present summary and discussion of the literature data for the influence of chelating agents and antioxidants on Cd-induced pathological conditions in Cd-intoxicated animals.

In Vitro Activity of Biometal(II) Complexes of Monensin Against Virus-Induced Transplantable Animal Tumors

Abstract: The anticancer properties of monensic acid (MonH) and its complexes with ions of Mg(II), Ca(II), Mn(II) and Co(II) were studied in cultured permanent cell lines originated from virus-induced transplantable tumors in chicken (hepatoma, LSCC-SF-Mc29) and in rat (sarcoma, LSR-SF-SR). The short-term experiments in monolayer adherent cells were performed by thiazolyl blue tetrazolium bromide (MTT) test (hepatoma and sarcoma cell lines) and neutral red (NR) uptake cytotoxicity assay (sarcoma cell line). The effect of monensin and corresponding complexes on the colony-forming ability of tumor cells was also evaluated. From the results obtained it can be concluded that all compounds significantly decrease the viability and proliferation of the treated cells in a time- and concentration-dependent manner, with metal(II) complexes being more effective than the non-coordinated ligand.

Sterically stabilized liposomes as a platform for salinomycin metal coordination compounds

Abstract: Sterically stabilized DPPC:CHOL:DSPE-PEG-2000 liposomal formulations of the lipophilic complexes of salinomycin with Na(I), K(I), Mn(II), Co(II), and Ni(II) ions were prepared by film-hydration method at different drug-to-DPPC molar ratios. For the K(I) and Na(I) complexes, optimal loading was established at a drug-to-DPPC molar ratio of 0.5:1, whereas for the Me(II) complexes, it was encountered at 0.1:1. DLS revealed uniform LUV populations (130-160 nm) with monomodal size distribution, further corroborated by AFM. Free and entrapped salinomycinates exhibited cytotoxicity in three human tumor cell lines, whereby the liposomal agents were superior vs. free complexes. DNA-fragmentation and flow cytometric assays showed that the cytotoxicity of free and liposomal salinomycinates is mediated by the induction of apoptosis and G1 arrest. The ability of the carriers to retain the bio-activity of the entrapped cargo gives us reason to conclude that the presented DPPC:CHOL:DSPE-PEG-2000 liposomes are suitable platforms for the salinomycin complexes, needing further evaluation and optimization.

Cytotoxicity of Monensic Acid and its Biometal(II) Complexes Against Anaerobic Bacterial Strain Clostridium Perfringens Spp.

Abstract: The cytotoxic properties of Monensic acid (MonH) and its biometal(II) complexes [M(Mon)2(H2O) 2] (M = Mg, Ca, Mn, Co, Ni, Zn) against the Gram-positive anaerobic bacterium Clostridium perfringens spp. are reported. All the studied Monensin complexes possess similar structures, but their activity varies in the concentration range from 0.17 μmol/L to 11.90 μmol/L Biometal(II) complexes improved the properties of Monensic acid in in vitro experiments, suggesting their possible practical application as more effective antibacterial agents than the non-coordinated antibiotic.