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The Study of Mechanisms of Hepatotoxic and Hepatoprotective Effects in a Model of Damaged Hepatocytes
Moravcová, Alena ; Lotková, Halka (advisor) ; Kmoníčková, Eva (referee) ; Kanďár, Roman (referee)
Liver damage has a variety of causes. Due to the role of liver in the metabolism of xenobiotics, liver damage is often caused by toxic substances. Despite the variety of causes, the mechanisms of damage may be common. Most often, oxidative stress is induced in the cell or important organelles are directly damaged. This leads to cell death, the initiation of an inflammatory response and the development of fibrosis. A major problem in Western civilization is Non Alcoholic Fatty Liver Disease (NAFLD), in which fat is stored in liver tissue. Steatotic hepatocytes may be more sensitive to damage compared to non-fatty ones. The study of hepatotoxicity and possible hepatoprotection requires suitable models for in vitro experiments. The first part of this work is therefore dedicated to the introduction of a model background using hepatocytes isolated from rat liver. First, we introduced a method of culturing hepatocytes in a sandwich and evaluated its benefit over cultivation in a monolayer, even for experiments lasting 48 hours, which are frequently used in our laboratory. Significant differences were recorded from day 4 of culture, when the sandwich model provides better preservation of morphological and functional parameters of hepatocytes. However, for our purposes of studying the mechanisms of...
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