Kindrat I. The molecular mechanisms of iron metabolism violation at liver damage

The thesis is devoted to the study of possible mechanisms of the ferrum compounds metabolism violation in the liver of the rats, the culture of liver cancer cells SK-HEP1, PLC/PRF/5, Hep3B, HepG2 and in the human HepaRG hepatoma cell line during toxins and carcinogens affect, diagnostics of early stages of the pathological conditions development under the influence of exogenous substances on the functional state of the liver using the parameters of the ferrum compounds metabolism. In the thesis the main ways of exchange of ferrum compounds and the possible mechanisms of their in vivo and in vitro metabolism disturbance are investigated for the effects of hepatotoxins and hepatocarcinogens such as metapyrilene hydrochloride, di-(2-ethylhexyl) phthalate (DEHP), 2-acetylaminophlourene and inorganic arsenic. The level of proteins and expression of the main genes involved in the metabolism of ferrum compounds and hepatotoxicity marker genes against the background of liver damage by xenobiotics has been established. The role of epigenetic mechanisms in dysregulation of the metabolism of ferrum compounds in liver cancer cells has been studied. The dynamics between the levels of ferrum ion and tumorigenic potential in liver cancer cells transfected with miR-152 were established.