We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
PURITAN MEDICAL

Download Mobile App




Novel Microreactor Enables Evaluation of Drug Toxicity on the Liver

By LabMedica International staff writers
Posted on 26 Aug 2015
Print article
Image: Liver-on-chip device and microscopic image of bionic liver (Photo courtesy of Dr. Yaakov Nahmias, The Hebrew University of Jerusalem).
Image: Liver-on-chip device and microscopic image of bionic liver (Photo courtesy of Dr. Yaakov Nahmias, The Hebrew University of Jerusalem).
A novel three-dimensional microreactor capable of maintaining metabolically active liver cells in vitro for over 28 days under stable oxygen gradients that mimic the in vivo microenvironment of the liver was used to determine why the painkiller acetaminophen (paracetamol) causes damage to this organ.

The liver tissue-based microreactor was the fruit of a project conducted by investigators at The Hebrew University of Jerusalem (Israel) and their colleagues at the Fraunhofer Institute for Cell Therapy and Immunology (Munich, Germany). The device was capable of maintaining the growth of liver cells under carefully controlled conditions for up to 28 days. Mitochondrial respiration was monitored using two-frequency phase modulation of phosphorescent microprobes embedded in the tissue. Phase modulation is focus independent and unaffected by cell death or migration.

The investigators reported in the June 4, 2015, online edition of the journal Archives of Toxicology that the device enabled the sensitive measurement of oxygen dynamics that revealed important information on the drug mechanism of action and transient subthreshold effects. Exposure to the widely used analgesic acetaminophen caused an immediate, reversible, dose-dependent loss of oxygen uptake followed by a slow, irreversible, dose-independent death. Transient loss of mitochondrial respiration was also detected below the threshold of acetaminophen toxicity.

It had been thought that liver toxicity was linked to acetaminophen's toxic byproduct NAPQI (N-acetyl-p-benzoquinone imine), which is normally produced only in small amounts and then almost immediately detoxified in the liver. However, under some conditions in which NAPQI is not effectively detoxified (usually in case of acetaminophen overdose), it causes severe damage to the liver. This becomes apparent three to four days after ingestion and may result in death from fulminant liver failure several days after the overdose. Results obtained with the liver bioreactor demonstrated the importance of tracing toxicity effects over time and suggested that NAPQI-independent targeting of mitochondrial complex III might be responsible for acetaminophen toxicity.

“The liver organs we created were less than a millimeter in diameter and survive for more than a month,” said senior author Dr. Yaakov Nahmias, professor of bioengineering at The Hebrew University of Jerusalem. “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. Because we placed sensors inside the tissue, we could detect small and fast changes in cellular respiration that nobody else could. Suddenly nothing we saw made sense.”

Related Links:

The Hebrew University of Jerusalem
Fraunhofer Institute for Cell Therapy and Immunology


Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
HLX
Complement 3 (C3) Test
GPP-100 C3 Kit
Gold Member
Xylazine Immunoassay Test
Xylazine ELISA

Print article

Channels

Clinical Chemistry

view channel
Image: Reaching speeds up to 6,000 RPM, this centrifuge forms the basis for a new type of inexpensive, POC biomedical test (Photo courtesy of Duke University)

POC Biomedical Test Spins Water Droplet Using Sound Waves for Cancer Detection

Exosomes, tiny cellular bioparticles carrying a specific set of proteins, lipids, and genetic materials, play a crucial role in cell communication and hold promise for non-invasive diagnostics.... Read more

Molecular Diagnostics

view channel
Image: The cobas Malaria test is the first FDA-approved molecular test to screen U.S. blood donors for malaria (Photo courtesy of Roche)

First FDA-Approved Molecular Test to Screen Blood Donors for Malaria Could Improve Patient Safety

Malaria, a serious illness that often leads to death, is spread by a specific mosquito species that infect humans with a parasite. Other transmission modes include blood transfusions, organ transplants,... Read more

Hematology

view channel
Image: The low-cost portable device rapidly identifies chemotherapy patients at risk of sepsis (Photo courtesy of 52North Health)

POC Finger-Prick Blood Test Determines Risk of Neutropenic Sepsis in Patients Undergoing Chemotherapy

Neutropenia, a decrease in neutrophils (a type of white blood cell crucial for fighting infections), is a frequent side effect of certain cancer treatments. This condition elevates the risk of infections,... Read more

Pathology

view channel
Image: The medical office procedure detects the key biomarker in Parkinson’s and related neurodegenerative diseases (Photo courtesy of BIDMC)

Simple Skin Biopsy Test Detects Parkinson’s and Related Neurodegenerative Diseases

Parkinson's disease and a group of related neurodegenerative disorders known as synucleinopathies impact millions globally. These conditions, including Parkinson’s disease (PD), dementia with Lewy bodies... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.