People who have liver disease can often develop a condition known as hepatic encephalopathy (huh-PAT-ick en-SEF-uh-LAH-puh-thee), which can potentially result in brain damage, personality changes, and problems with learning ability due to high levels of ammonia in the bloodstream. The condition often occurs with cirrhosis, in which the liver cannot efficiently cleanse the body of toxins and drugs.1
Now, a group of doctors in Spain say they think they know why these neurological problems occur, and say a well-known medicine might be able to help.2 Tests in people, however, haven't been done yet.
Viagra for Liver-Related Complications?
The investigators were headed by Vicente Felipo, PhD, director of the Laboratory of Neurobiology at the Fundacion Valenciana de Investigaciones Biomedicas in Valencia, Spain. Felipo's team had speculated that the neurological problems caused by liver disease were due to a defect in a particular chain of events in the brain. This series of events results in the production of a major molecule in the brain necessary for learning ability (cGMP) which breaks down when liver disease-related neurological conditions occur.
Since it was already well known that sildenafil, widely known as Viagra, helps restore this RNA component,3 and allows it to build up in the body, Felipo's team thought that it might help treat the learning disabilities and other neurological symptoms sometimes seen in liver disease. They tested their theory in a group of rats.
Four groups of rats were tested:
• Rats with portacavil shunts—This is a common therapy for portal hypertension, or abnormally high blood pressure in the liver due to the scarring (cirrhosis) that occurs in liver disease. An artificial opening is created in the veins that feed the liver, helping to ease the high blood pressure. Portal hypertension is also believed to be one of the causes of hepatic encephalopathy.
• Rats with portacavil shunts which were given doses of sildenafil
• Rats fed a diet containing ammonium (High levels of ammonia are thought to be involved in the processes that lead to learning disabilities associated with liver disease.)
• Rats fed an ammonium-containing diet combined with doses of sildenafil
Outcomes in these four compares were then compared with each other. Essentially, the rodents with portacaval shunts and those given a diet high in ammonium—both without sildenafil—were used as comparison groups to the groups of rats given the medication. The rats were tested by determining whether they could find their way out of a special maze.
The Effect of Viagra on the Brain
Results showed that while rats with the portacaval shunts showed a reduced learning ability, those with both the shunt and doses of sildenafil showed that they were able to learn how to maneuver the maze without difficulty. Tests showed that levels of cGMP also rose in those rats given sildenafil compared to those without the drug.
Rats with very high levels of ammonia in their blood were also tested with and without sildenafil. The study found that those given the drug had better learning ability compared to those without it. But it did not affect levels of ammonia in the animals.
Felipo's team noted that the common denominator in all their tests of learning disability was that high ammonia levels played a key role in all cases. Thus, they concluded that there was a direct link between blood levels of ammonia and learning disability.
The fact that a drug like sildenafil can restore learning ability in rats with liver disease and in those with high ammonia levels "may have important clinical implications for the treatment of the impairment of intellectual function present in patients with evident hepatic encephalopathy, but also in patients with minimal hepatic encephalopathy," Felipo and his fellow researchers pointed out.
1. American Gastroenterological Association. Cirrhosis of the Liver. Available at: http://www.gastro.org/clinicalRes/brochures/cirrhosis.html. Accessed January 27, 2005.
2. Erceg S, Monfort P, Hernandez-Viadel M, Rodrigo R, Montoliu C, Felipo V. Oral administration of sildenafil restores learning ability in rates with hyperammonemia and with portacaval shunts. Hepatology 2005 Jan 19;41(2):299-306 [Epub ahead of print].
3. Preston IR, Hill NS, Gambrdella LS, Warburton RR, Klinger JR. Synergistic effects of ANP and sildenafil on cGMP levels and amelioration of acute hypoxic pulmonary hypertension. Exp Biol Med (Maywood) 2004 Oct;229(9):920-5.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
