Navigation Links
Rutgers, Massachusetts General investigators find novel way to prevent drug-induced liver injury
Date:1/15/2012

NEW BRUNSWICK, N.J. Rutgers University and Massachusetts General Hospital (MGH) investigators have developed a novel strategy to protect the liver from drug-induced injury and improve associated drug safety.

In a report receiving advance online publication in the journal Nature Biotechnology, the team reports that inhibiting a type of cell-to-cell communication can protect against damage caused by liver-toxic drugs such as acetaminophen.

"Our findings suggest that this therapy could be a clinically viable strategy for treating patients with drug-induced liver injury," said Suraj Patel a postdoctoral researcher in the Center for Engineering in Medicine at MGH and the paper's lead author. "This work also has the potential to change the way drugs are developed and formulated, which could improve drug safety by providing medications with reduced risk of liver toxicity."

Drug-induced liver injury is the most common cause of acute liver failure in the U.S. and is also the most frequent reason for abandoning drugs early in development or withdrawing them from the market. Liver toxicity limits the development of many therapeutic compounds and presents major challenges to both clinical medicine and to the pharmaceutical industry.

Since no pharmaceutical strategies currently exist for preventing drug-induced liver injury, treatment options are limited to discontinuing the offending drug, supportive care and transplantation for end-stage liver failure.

The researchers investigated an approach that targets a liver's gap junctions hollow multimolecular channels that connect neighboring cells and allow direct communication between coupled cells. In the heart, gap junctions propagate the electrical activity required for synchronized contraction, but their role in the liver has not been well understood

Recent work has shown that gap junctions spread immune signals from injured liver cells to surrounding undamaged cells, amplifying inflammation and injury. The current study examined inhibiting the action of 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 acetaminophen, a commonly used medication best known under the Tylenol brand name. Acetaminophen overdoses are the most frequent cause of drug-induced liver injury.

Compared to normal mice, those lacking liver gap junctions were fully 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 injury and prevented their death.

"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," said Martin Yarmush, senior author of the report and the Paul and Mary Monroe Professor of Biomedical Engineering at Rutgers. "However, before we can think about applying this approach to patients, we need to know more about any off-target effects of gap junction inhibitors and better understand the long-term ramifications of temporarily blocking liver-specific gap junction channels."

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.


'/>"/>
Contact: Carl Blesch
cblesch@ur.rutgers.edu
732-932-7084 x616
Rutgers University
Source:Eurekalert  

Related medicine news :

1. Even privately insured have hard time getting psychiatric care in Massachusetts: Harvard study
2. Massachusetts health-care reform increased access to care, particularly among disadvantaged
3. Massachusetts General Hospital, Iacocca Foundation announce promising results of Phase I diabetes trial
4. Study examines impact of Massachusetts health law on emergency department visits
5. Support for Massachusetts landmark health reform law rises in 2011
6. Massachusetts Study Shows Sharp Rise in Early Autism Diagnoses
7. Season of birth and celiac disease in Massachusetts children
8. Massachusetts reform hasnt stopped medical bankruptcies: Harvard study
9. Massachusetts General Hospital leading nationwide, comparative study of common bipolar medications
10. Massachusetts physician groups improving patient experience, study finds
11. Massachusetts Institute of Technology IDs new cancer drug target
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Rutgers, Massachusetts General investigators find novel way to prevent drug-induced liver injury
(Date:3/30/2021)... , ... March 29, 2021 , ... ... the 21st Century , A Virtual Workshop Presented by WCG FDAnews and Cerulean ... 4:30 pm EDT, https://wcg.swoogo.com/modern-sop-and-quality-systems , Are one’s SOPs written for the ...
(Date:3/30/2021)... ... March 29, 2021 , ... According to data released ... reproductive age (13-44) in need of publicly funded contraception live in counties impacted by ... Colorado’s 64 counties have lost some of their Title X resources. , The ...
(Date:3/30/2021)... ... March 29, 2021 , ... Health Literacy Innovations (HLI), a ... confusion due to low health literacy today announces a new partnership with the ... work with ACAP’s member Safety Net Health Plans, those that provide comprehensive health ...
(Date:3/30/2021)... ... ... Dr. Colin Campbell is proud to announce the 1 year anniversary in their new state ... internal medicine and is a primary care specialist who has been practicing for 23 years. ... keep South Jersey healthy one patient at a time. , “Over the past year, Dr. ...
(Date:3/30/2021)... ... March 30, 2021 , ... The COVID-19 ... and survivors; their families; and their caregivers. Crossroads4Hope is addressing the needs of ... emotional support system, MyGo2Support, which meets needs of people impacted by cancer, no ...
Breaking Medicine News(10 mins):
(Date:3/30/2021)... ... March 29, 2021 , ... The University of Texas Health Science Center ... San Antonio Multispecialty and Research Hospital, a destination center for research and treatment of ... In a nod to the COVID-19 pandemic, the ceremony was held virtually. , William ...
(Date:3/30/2021)... ... March 29, 2021 , ... Iora Health ... primary care, has partnered with Devoted Health , one of the fastest-growing ... across Maricopa County and provides seniors with the highest-quality care and experience possible, ...
(Date:3/30/2021)... CITY (PRWEB) , ... March 29, 2021 , ... ... has joined the Vaccine Credential Initiative (VCI), a group bringing together leading health ... record of vaccination status, based on open, interoperable standards. By joining the VCI ...
Breaking Medicine Technology: