How can physicists contribute to dealing with drug-induced liver injury? The answer to this question is, for example, by applying cutting-edge imagining techniques. Researchers from the Institute of Physic of the Czech Academy of Sciences have joined an international interdisciplinary research team which is conducting a research to generate new knowledge and approaches to dealing with drug-induced liver injury, aiming to create a liver model for timely detection of drug toxicity. A comprehensive interdisciplinary research summary of this subject was published in the prestigious Journal of Hepatology.
The contribution to this research, made by the researchers from the Department of Optical and Biophysical Systems of the Institute of Physics, Dr. Alexander Dejneka and Dr. Oleg Lunov, consisted of establishing a procedure for studying liver cells in 3D resolution in real-time and observing them on a sub-cellular level, using optical and fluorescence microscopy, namely the Institute’s superresolution confocal microscope based on a spinning disc. “These non-invasive technologies improve cellular system imaging, and they can be very helpful when screening drug-induced liver injury models”, Dr. Oleg Lunov said.
Interval imagining of mitochondrial damage in liver cells, provided with a superresolution spinning disc microscope.
Pre-clinical drug-induced toxicity screening has so far relied on traditional in-vitro tools, which test the influence of a tested preparation on cell viability. However, these tests are unable to detect the frequent changes occurring if a cell adapts to a drug-induced injury. Along with the biochemical and molecular biology methods, the imagining techniques have provided another useful tool for making detailed cellular process observations.
The published research gave a detailed description of how researchers should evaluate liver injury while testing drug safety. The study also emphasised that there are no reliable drug-induced injury models available that are accepted by regulatory bodies in Europe and USA. “Drug-induced liver injury accounts for up to 30 % of cases when a drug is not placed on the market. That’s why we feel the need to develop new physiologically relevant pre-clinical models for drug screening for liver injury,“ Dr. Alexandr Dejneka said.
This unique multidisciplinary research is carried out as part of the European Drug-Induced Liver Injury Network PRO-EURO-DILI-NET, with active participation of the researchers from the Institute of Physics of the Czech Academy of Sciences. The objectives of the PRO-EURO-DILI-NET are to create a unique, co-operative, interdisciplinary European-based DILI network of stakeholders to coordinate efforts in DILI, to facilitate bi-directional exchange of discovered knowledge and generated hypotheses among different disciplines, and to promote clinically impactful knowledge discovery and its translation into clinical practice.
Literature:
Jose C. Fernandez-Checa et al., Advanced preclinical models for evaluation of drug-induced liver injury – consensus statement by the European Drug-Induced Liver Injury Network [PRO-EURO-DILI-NET], Journal of Hepatology, https://doi.org/10.1016/j.jhep.2021.06.021
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