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Researchers: Acetaminophen toxic at lower levels than thought

The discovery was made while designing a liver-on-a-chip to replace animal experiments used to study drug toxicity.

By
Stephen Feller
The liver-on-a-chip researchers recently developed is hope to be able to replace animal testing of products for toxicity in humans. Photo by Yaakov Nahmias/Hebrew University
The liver-on-a-chip researchers recently developed is hope to be able to replace animal testing of products for toxicity in humans. Photo by Yaakov Nahmias/Hebrew University

JERUSALEM, Aug. 17 (UPI) -- Researchers have found that far lower levels of acetaminophen can be toxic to humans than previously thought, shedding light on how people can easily overdose on the commonly used over-the-counter painkiller.

The discovery was made during the development of liver-on-a-chip technology to be used for pharmaceutical and other safety testing. The concept is that, rather than testing products on animals, companies and researchers can use tiny versions of the human liver for testing.

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"We knew that acetaminophen can cause nephrotoxicity as well as rare but serious skin reactions, but up until now, we didn't really understand the mechanism of such an effect," said Oren Shibolet, head of the liver unit at Tel-Aviv Sourasky Medical Center, in a press release. "This new technology provides exceptional insight into drug toxicity, and could in fact transform current practice."

Researchers grew liver organs less than a millimeter in diameter which can survive for about a month -- normally, human cells cannot survive outside the body for more than a few days. Where this chip technology differs from some others, said Dr. Yaakov Nahmias, a professor at Hebrew University, is the inclusion of nanotechnology-based sensors within in the tissues.

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"We realized that because we are building the organs ourselves, we are not limited to biology, and could introduce electronic and optical sensors to the tissue itself. Essentially we are building bionic organs on a chip," said Nahmias. "Because we placed sensors inside the tissue, we could detect small and fast changes in cellular respiration that nobody else could."

This allowed the researchers to make the discovery about much lower levels of acetaminophen, the active ingredient in Tylenol, being more toxic than had previously been thought. They were able to detect the drug interfering with cellular respiration, explaining what toxic levels of acetaminophen do to the liver.

The study is published in Archives of Toxicology.

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