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Mass. General researchers find novel way to prevent drug-induced liver injury
Date:1/15/2012

ding undamaged cells, amplifying overall inflammation and injury. The current study was designed to discover the potential of targeting liver-specific gap junctions to limit drug-induced liver injury.

The researchers first used a strain of genetically mutated mice that lack a particular liver-specific gap junction. The mice were administered various liver-toxic drugs, such as the commonly used medicine acetaminophen. Overdoses of acetaminophen, which is best known under the brand name Tylenol, are the most frequent cause of drug-induced liver injury. Compared to normal mice, those lacking liver gap junctions were protected against liver damage, inflammation and death caused by administration of liver-toxic drugs.

The team then identified a small-molecule inhibitor of liver gap junctions that, when given with or even after the toxic drugs, protected the livers of normal mice against any injury and prevented their death. Additionally, cell culture experiments indicated that blocking gap junctions limited the spread through liver cells of damaging free radicals and oxidative stress, suggesting a possible mechanism for the observed protection.

"This finding is very exciting and potentially very powerful from a number of basic science and clinical application standpoints, which we are continuing to explore," says Martin Yarmush, MD, PhD, director of the MGH Center for Engineering in Medicine and senior author of the study. "However, before we can think about applying this approach to patients, we need to know more about any off-target effects of these gap junction inhibitors and better understand the long-term ramifications of temporarily blocking liver-specific gap junction channels."

A patent related to the work has been filed by Partners Healthcare, and an early stage biotechnology company, Heprotech Inc., was recently established to develop this new technology further. "The findings from this work suggest a novel drug devel
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
Source:Eurekalert

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