Molecular and Cellular Toxicology Group

for In Vitro Research of Toxic and Protective Actions of Xenobiotics

The research of our group is focused on diverse aspects of molecular and cellular toxicology. Using cultured cells (both isolated primary cell cultures as well as permanent cell lines) we aim at advancing the mechanistic understanding of various types of cellular injuries and actions of xenobiotic substances. We study differences in actions of various agents in different cell types and involvement of specific cell death pathways, including apoptosis - the most important type of the programmed cell death. We also focus on mitochondria - organelles crucial for cell death and survival and key mediators of the intrinsic apoptotic pathway.

Most of our research projects aim at drug-induced cardiovascular toxicity, particularly the cardiotoxicity of anthracycline anticancer drugs, but we also examine cardiotoxic properties of other anticancer drugs (and/or their combinations with anthracyclines). Our next important topics are cardiac oxidative stress, catecholamine cardiotoxicity and the role of redox-active iron and other transition metals in oxidative stress and toxicity. We are engaged in several collaborative projects aimed at development of potential cardioprotective agents but also study novel potential anticancer agents with iron-chelating and photodynamic properties.

Isolation of the rat neonatal ventricular cardiomyocytes 

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Cardiomyocytes in cell culture

In most research topics, our in vitro cellular studies are coupled with experiments in collaborating laboratories using appropriate in vivo models and the pharmacodynamic / toxicodynamic data are often coupled with pharmaco-/toxico-kinetic studies. Predominantly, this collaborative research takes place within the network of several groups joined in the Charles University Research Center for the Study of Toxic and Protective Effects of Drugs on Cardiovascular System. This center integrates approaches of biochemistry, medicinal chemistry, pharmacology, toxicology and bioanalytical chemistry, in order to bring together complementary skills, knowledge, and resources to jointly address the research problems.

We are always open to further collaborations in areas of drug-induced cardiotoxicity as well as other research topics that can make use of our expertise and/or instrumentation.

H9c2 rat cardiomyoblast-derived cell line in the process of the toxic action of anthracycline daunorubicin. Cells were stained with JC-1 fluorescent probe (Molecular Probes). While punctuate red emission reflects mitochondrial inner membrane potential (ΔΨm)-dependent accumulation of probe dimers in actively respiring mitochondria, diffuse cytosolic green fluorescence indicates monomers of the probe released into cytoplasm after mitochondrial depolarization, lack of fluorescence is indicative for probe release from necrotic or late-stage apoptotic cells.

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