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:1/23/2017)... ... January 23, 2017 , ... Moisture measurement is a necessary ... is paramount to success. Selecting an inappropriate measurement method can cause costly errors, ... the same equipment. Rare or expensive substances are wasted and production may even ...
(Date:1/23/2017)... ... January 23, 2017 , ... Old School Labs™, makers ... Mr. Olympia Classic Physique bodybuilder Breon Ansley to its growing team of brand ambassadors. ... bodybuilder in 2012 and in less than a year was able to turn professional, ...
(Date:1/23/2017)... ... 23, 2017 , ... “The Inn at the Mill”: a story of love and redemption, ... to become happy and content. , “The Inn at the Mill” is the creation ... Germany and Vermont and is now living in Berks County on Crow Hill. ...
(Date:1/23/2017)... ... January 23, 2017 , ... “Life Under Blankets”: ... from an early age. “Life Under Blankets” is the creation of published author, Kimberly ... Circle Campus in Chicago. She went on to pursue a master’s degree in education ...
(Date:1/22/2017)... ... January 22, 2017 , ... Phytocéane invites clients to take an exotic journey ... world with ZANZIBAR MILKY CREAM. Inspired by the beauty of Zanzibar, a Tanzanian archipelago ... and moisturizing vegetal coral to create this gentle, velvety body cream to envelop the ...
Breaking Medicine News(10 mins):
(Date:1/23/2017)... Massachusetts , January 23, 2017 Longer life ... growth in the global market for medical device technologies. BCC Research ... in the Asia-Pacific region, should see strong growth ... and rising disposable incomes. Continue Reading ... ...
(Date:1/23/2017)... SAN DIEGO , 23 janvier 2017  ResMed ... Winter Haven , Floride) ont annoncé aujourd,hui qu,ils se ... les litiges existants entre les parties. BMC et 3B ... de paiements de droits à ResMed, et ResMed effectuera ... à 3B pour clore le litige de Floride entre ...
(Date:1/23/2017)... and PALMA, Spain , January ... S.L., a clinical-stage biopharmaceutical company focused on treatments ... patient has been enrolled in the Phase IIb ... for the treatment of cardiovascular calcification (CVC) in ... Most ESRD patients, in the last stage of ...
Breaking Medicine Technology: