June 1, 2011 New research raises the possibility that the critically short supply of livers for organ donation could be expanded by treating so-called "marginal" livers with a substance that protects them from damage after being connected to recipients' blood supplies.
The report appears in ACS' journal Molecular Pharmaceutics.
Ram Mahato and colleagues note that the need for liver transplants has grown over the years, though the number of available livers has not. Currently, more than 16,000 people are waiting for a liver in the U.S., but less than 7,000 liver transplants were performed during the entire year of 2010. This shortage has led organ transplant teams to consider using marginal, or damaged, livers, such as those with cholestasis -- a build-up of bile. But transplanting a damaged liver has risks, including a higher risk that the organ will fail. To overcome this challenge, the researchers utilized a hedgehog-signaling inhibitor to increase the odds of a successful liver transplant.
They found that a compound called cyclopamine prevented further injury to cholestatic livers after the blood supply was cut off then returned -- a situation similar to what transplanted livers undergo. The research was performed in rats, which are stand-ins for humans in the laboratory. It provided "convincing evidence" that cyclopamine may protect cholestatic livers from additional damage after a transplant procedure and improve clinical outcomes for the patients.
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- Akshay Pratap, Ravikiran Panakanti, Ningning Yang, Ramasubramanian Lakshmi, Kian A Modanlou, James D Eason, Ram I. Mahato. Cyclopamine attenuates acute warm ischemia reperfusion injury in cholestatic rat liver: Hope for marginal livers. Molecular Pharmaceutics, 2011; 110414140219042 DOI: 10.1021/mp200115v
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