Assessment of the safety of drugs and cosmetics is one of the most important stages in their development.
In recent years, researchers have clearly understood that animal experiments do not allow 100% to accurately predict the response of the human body to an experimental agent.
Therefore, it is necessary to replace laboratory animals with something more reliable.
And this is not to mention the ethical aspects of experiments on living beings.
Recently, European regulators started administrative methods to restrict the use of animals in cosmetic tests, blocking the development of a number of products by the famous companies L'Oreal and Estee Lauder. This led to the fact that leading companies around the world began investing millions in the creation of microchips that mimic the response of the human body to the experimental product.
The main obstacle that faced the researchers was the low viability of human cells outside the body. To solve this problem, scientists from the Hebrew University of Jerusalem (Israel) and the Institute for Cellular Therapy and Immunology of Fraunhofer (Germany) created a microchip with liver cells that completely mimics the physiology of human hepatocytes.
"Microscopic models of the liver developed by us have less than 1 millimeter in diameter and live more than a month. Although other groups of scientists have obtained similar results, our breakthrough is the use of nanotechnological biosensors inside the chips. We realized that electronic and optical sensors inside the tissue are needed for effective control of the parameters. In fact, we have made a full-fledged bionic liver, permeated with microelectronics, "explains Professor Yaakov Nahmias, lead author of the latest study and director of the Alexander Grass Bioengineering Center at the Hebrew University.
During the first experiments with microchips, optoelectronic sensors inside living tissue allowed scientists to study in detail the toxic effect of paracetamol on the liver. Comparing these results with the clinical data on a long-studied drug, the German-Israeli team concluded that new microchips could well replace laboratory animals.
"Since we installed these sensors right inside the tissue, we were able to observe the slightest changes in cellular respiration and other processes that no one else could see. It's even better than using animal models, "says Nahmias.
In particular, the authors found that paracetamol is able to block the cellular respiration of hepatocytes much more quickly and in much smaller doses than previously thought. According to the current concept, paracetamol is first converted to a toxic metabolite called N-acetyl-p-benzylquinonimine (NAPQI), which already affects liver cells. Since the liver is capable of neutralizing NAPQI, scientists believed that the toxic effect of paracetamol on the liver occurs only with the use of large doses of the drug.
It turned out that this is not entirely true. The latest study turned 50 years of work of pharmacologists upside down. As reported in the journal Archives of Toxicology, the paracetamol molecule itself is capable of blocking cellular respiration, so the liver is damaged even by taking relatively small doses of this drug substance.
"This is an amazing opportunity.
We knew about the nephrotoxicity of paracetamol and its ability to cause serious skin reactions, but until today we really did not understand the mechanism of the toxic effect of this substance on the liver. The new technology gave us the opportunity to study the effect of drugs on cells deeper, which, in fact, can turn medical practice, "said Professor Oren Shibolet, head of the department of hepatology at the Suraski Medical Center in Tel Aviv.
medbe. en.
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