Summary
Scientiest still remain baffled at why liver failure sometimes leads to brain damage in patients. But new research using the drug Viagra may help unravel the mystery. Laboratory rats given Viagra did not show signs of brain damage after their livers were intentionally impaired. Scientists still have work to do to completely solve the puzzle, but the research indicates they're on the right track.
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A study involving rats reveals the mechanism responsible for learning impairment due to liver failure and shows that sildenafil restores cognitive function.
Liver disease sometimes causes hepatic encephalopathy, which involves brain damage, personality changes, and intellectual impairment due to hyperammonemia (high levels of ammonia in the blood).
In a new study led by Vicente Felipo of the Laboratory of Neurobiology at the Fundacion Valenciana de Investigaciones Biomedicas in Valencia, Spain and published in the February 2005 issue of Hepatology, researchers hypothesized that impaired learning was due to a defect in the glutamate- nitric oxide-cGMP pathway in the brain and that administering sildenafil to increase cGMP would restore learning ability.
and rats that were fed the diet and given sildenafil.
They also used control groups consisting of rats fed a normal diet both with and without sildenafil.
All animals were subjected to a maze learning test four weeks following surgery or from the date when drug treatment began.
Results showed that while rats with the portacaval shunt showed a reduced learning ability, treatment of shunted rats with sildenafil restored their ability to learn.
Tests showed that the concentration of cGMP was reduced in the extracellular fluid in brains of shunted rats compared with controls and that treatment with sildenafil restored levels of cGMP in these animals.
"The fact that rats with portacaval anastomosis [shunts] or with hyperammonemia without
liver failure show the same alterations in the function of the [glutamate-nitric oxide- cGMP] pathway, extracellular cGMP and learning ability indicates that hyperammonemia, which is the only common alteration in both models, is responsible for the alteration of the function of the pathway and, subsequently, of the impairment of learning ability," the authors state.
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Tuesday, January 25, 2005
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