How do drugs affect my liver

How drugs damage the liver

bmbf.de: Why is the liver important for our body?

Jan Hengstler: Everything we swallow has to pass through the liver before it gets into the general bloodstream. It detoxifies many things that are harmful to the organism. As a result, however, she is always in danger: She gets all the toxins in a concentrated load.

More than five million people in Germany suffer from liver disease. How can these diseases arise?

The causes are varied: alcohol or obesity are often involved. Then there are various viral diseases that cause liver damage, but also hereditary liver diseases. And liver damage can also be caused by chemicals or drugs.

They examine liver damage from drugs. What exactly happens there?

Medicines usually reach the liver in high concentrations. There they can disrupt various functions or lead to the death of liver cells.

But the liver can regenerate ...

Yes, in the course of evolution, herbivores and omnivores like us have got used to ingesting poisonous plants. As a result, the liver has learned to repair one-off damage. It can even die off up to half of the liver tissue and build up again afterwards. However, regeneration does not work as well if toxic substances repeatedly enter the body. This can lead to scarring, which changes the architecture of the organ. And in the worst case, this leads to cirrhosis of the liver, which can be fatal.

It can even die off up to half of the liver tissue and build up again afterwards.

Professor Jan Hengstler

They analyze these processes using the example of paracetamol, a very common and non-prescription drug. When is it harmful?

Paracetamol is absolutely harmless as a drug in the therapeutic dose. You can easily take up to three grams a day for fever or pain. However, if this limit is exceeded just a little, liver damage is very common. Paracetamol is so interesting as a model substance for research because it is known exactly when it becomes toxic. This helps us to understand how we can also tell whether other active ingredients are harmful.

How do you test the effects of drugs on people?

We take human liver cells and expose them to a specific concentration of an active ingredient in the laboratory. Many drugs are known to have a blood concentration at which they are toxic. If we can also observe damage to the cell culture at exactly this value, transferring it from the cell culture model to humans is easy. For many substances, however, it is more complicated. They harm people even at a lower concentration.

What do you do in these cases?

We look for signs of whether the liver cells in culture are already in a state of stress at the lower concentrations. These can be changed processes and functions of the cells. We search for these in a targeted manner and then feed the results from these tests into computer models in order to take other physiological properties of the liver into account. For example, we simulate the metabolism of the liver on the computer: How much substance arrives where in the organ, how is it metabolized and when does an active substance lead to the death of cells or other damage.

With the combination of cell culture tests and computer models, we want to predict whether and when a new substance is harmful.

Professor Jan Hengstler

What is the aim of your research?

With the combination of cell culture tests and computer models, we want to predict whether and when a new substance is harmful. Such a test strategy is faster and cheaper than previous methods - and could also make drug tests even safer.

Could your predictions also help replace animal testing?

That is our goal, even if there is still a lot to do along the way. If our tests have run alongside the legally required test for a few years and you can see that they would have predicted this just as well, then this is in principle possible.

What can each of us do to save our liver?

Two things in particular help: a balanced diet and regular exercise. Almost a third of Germans now have fatty liver - that's unbelievable. The liver then still works, but is much more susceptible to certain liver diseases such as cirrhosis. The tumor risk also increases. Fortunately, the fat from the liver can also be broken down again. So it's always worth starting a healthy life.

Professor Jan Hengstler heads the toxicology and systems toxicology department at the Leibniz Institute for Labor Research at TU Dortmund University. His main research interests include the risk assessment of drugs and chemicals. He is supported in several projects by the Federal Ministry of Education and Research.