Archives: Projekti

Head: Vladimira Vađić, 2008-2014

MINISTRY OF SCIENCE, EDUCATION AND SPORTS OF THE REPUBLIC OF CROATIA (2007-2014)

Principal Investigator: Jasmina Sabolović

SUMMARY
Low-molecular-weight transition metal complexes with amino acids, peptides and proteins are supposed to be a part of exchangeable physiological pool for the storage and transport of essential metals for most tissues in living organisms. The binding affinity between a metal and a ligand affects the biological, chemical and toxicological properties of the metal. Redox potential, the metal-ligand bonding reversibility, ionic species distribution and stability constants in solutions can be measured by voltammetry, whereas the structural properties can be predicted and reproduced with theoretical molecular modelling methods. The Cu(II) complexes with Gly, Ala, Val, Leu, Ile show two-electron and quasi-reversible redox electrochemical behaviour in aqueous solution under physiological conditions. The changes between the vacuum geometries (calculated using quantum chemical methods) and experimental X-ray crystalline geometries of 7 Cu(II) amino acid complexes were revealed and attributed to the ligand-based strain and crystal lattice effects. These geometry changes can be simulated with our original molecular mechanics (MM) model and force field (named FFW) developed to reliably reproduce the experimental crystal and ab initio vacuum structures by geometry optimisation of a molecule in simulated crystalline surroundings and as an isolated system, respectively. By now FFW has been parametrised for bis-Cu(II) complexes with Gly, Ala, Val, Leu, Ile and their alkyl derivatives. The project goals are to gain new experimental and theoretical evidence of the physico-chemical properties of essential Cu and Zn and toxic Pb and Cd metal complexes with bioligands (amino acids, peptides) using theoretical methods (MM, molecular dynamics, quantum chemistry) and experimental methods (voltammetry, X-ray diffraction), and to predict and simulate the complexes’ properties in crystal, vacuum, and solution. Method development and the interplay of the experimental and theoretical results will contribute to the understanding of the metal-bioligand interactions and properties in different physico-chemical conditions. We expect that FFW enlarged with new empirical parameters for the Cu(II) and Zn(II) amino acidates will reliably predict the complexes” properties in a solution. The force field efficacy will be validated by the ability to reproduce experimental results. The proposed studies may lead to get new drugs for prevention of disturbed transition-metal metabolism effects in vivo.

Head: Vlasta Drevenkar, 2010

The Ministry of Science, Education and Sports of the Republic of Croatia (2002-2006)

Principal investigator: Maja Blanuša

SUMMARY
In the forthcoming period factors influencing an increase in toxic metal concentrations in the body at an early age will be studied on suckling rats. Special attention will be given to some dietary components like calcium, selenium, and vitamin C. New data on the interaction of essential dietary components with toxic metals (lead, cadmium, mercury) will be obtained. The efficiency of chelation therapy at an early age, especially during ongoing exposure to toxic metals, is investigated as a contribution to treatment of metal poisoning in children. The following chelating agents are used: meso-2,3-dimercaptosuccinic acid (DMSA), sodium-(RS)-2,3-dimercapto-1-propanesulfonate (DMPS) and calcium-trisodium-diethylenetriaminepentaacetate (DTPA). Dietary supplementation and/or chelation therapy are administered during or after exposure to lead or cadmium to obtain highest reduction in tissue concentrations of these toxic metals. The health effect of such treatments and tissue essential element concentrations will be also evaluated. The efficiency of combined chelation therapy with DMSA and DTPA will be evaluated in older rats for treatment of acute cadmium poisoning. The influence of selenium on the efficiency of chelating agents, DMSA and DMPS for reducing tissue mercury concentrations will be also studied. The effect of cigarette smoking on concentrations of metals and steroid hormones is evaluating in human placental tissues. For monitoring purposes the ratio of heavy metals in soil, plants (mushrooms), and isopods is measured. The importance of calcium intake during the suckling period for bone mineral contents in adult age is assessed in an animal model. In epidemiological studies the effects of environmental and nutritional factors as compared to genetic factors on bone mineral content will be estimated in children and adults.

Head: Vladimira Vađić, 1963-2014

MINISTRY OF SCIENCE, EDUCATION AND SPORTS OF THE REPUBLIC OF CROATIA (2007-2014)

Principal Investigator: Ivančica Trošić

SUMMARY
Electromagnetic radiation (EM) of microwave frequencies in the range of 300 MHz-3000 MHz (MW) has become one of the major physical environmental pollutants. This raises concern about health hazards related to the interaction between microwave EM fields and life processes. Depending on the field strength, frequency, wave form, modulation, and duration of exposure, microwave radiation is absorbed in the molecules and manifests as a change in vibration energy or heat. So far, studies of microwave radiation risk in a variety of life forms have produced controversial results. The effects that have been positively established include changes in the cell membrane functionality, calcium metabolism, cellular signal communication, cell proliferation and differentiation, proto-oncogens, heat-shock protein activation, and the cell death. Beside genotoxic action, microwaves seem to have a neurodegenerative potential. Studies in the field of bioelectromagnetism should aim at defining the biological markers of target systems susceptibility to the MW radiation at nonthermal level. The biomarkers of susceptibility and the biomarkers of the effect of low-intensity microwave radiation will be investigated using complex approach, including the basic experimental model; cell cultures, and experimental animals. The study is expected to reveal the indicators of harmful effects of low-intensity microwave radiation in vivo. The mechanisms of MW radiation activity at the cellular and subcellular level will be examined in vitro using continuous cell cultures. Cell survival, proliferation and colony-forming ability will be examined after microwave exposure in addition to macromolecular structures, and cytoskeleton proteins, microtubules, intermediate or actin filaments. The results will give some direction to the in vivo investigation, which in turn will reveal matching target cells suitable to create a primary MW-sensitive cell culture. With an adequate methodological approach, such primary cell culture could help to determine biomarkers of the effects of non-thermal MW radiation in vivo. Biological effects which reveal physical and chemical changes at the molecular, cell or tissue level might disturb homeostasis and stimulate whole body response.