Projects

Dr Đurđica Jovović, dr Zoran Miloradović, dr Nevena Mihailović-Stanojević, dr Jelica Grujić Milanović, dr Milan Ivanov, dr Danijela Karanović, dr Una Jovana Vajić

University of Belgrade, Institute for Medical Research, Institute of national importance for the Republic of Serbia

One of the main objectives of the project was to investigate the effects of natural and synthetic antioxidant substances in hypertension and acute and chronic renal failure. The effects of using olive extract (which contains potent antioxidants) on animal models of essential hypertension and kidney disease were also studied. Part of the project also included testing the beneficial effects of resveratrol, a potent antioxidant molecule isolated from grapes, in models of experimental essential and malignant hypertension. The relationship between the renin-angiotensin system and oxidative stress in the development of post-ischemic acute renal failure and chronic kidney disease was investigated. We used rats with essential hypertension in which we induced acute kidney injury or adriamycin-induced renal glomerulosclerosis and administered angiotensin-2 receptor blockers and synthetic analogues of the enzyme superoxide dismutase. The results of these studies have revealed to us inadequately known mechanisms of action of oxidative stress and the renin-angiotensin system in hypertension, acute renal failure, and chronic kidney disease.

Teodora Dragojević, Tijana Subotički, Miloš Diklić, Olivera Mitrović Ajtić, Vladan Čokić

The aim of this project is to investigate potential involvement of NOS enzymes in the molecular mechanism of action of the chemotherapeutic agent hydroxyurea, which is used for the treatment of myeloproliferative neoplasms, chronic myeloid leukemia, and solid tumors. Obtained results should answer the following scientific questions: 1) if HU activates NOS enzymes via direct interaction or indirectly, 2) if inhibition or reduced protein expression of NOS enzymes at least partially rescues HU-induced proliferation block and apoptosis and, 3) which of the NOS isoforms is involved in these processes? Primary mouse erythroid cells isolated from bone marrow and human erythroleukemic cell lines will be used in this study. The relevance of the results obtained in vitro will be confirmed by in vivo treatment of Nos2- or Nos3- deficient mice. Comprehensive knowledge of the molecular mechanism of HU might help improve its beneficial properties and decrease adverse effects.