Grapefruit compound may help combat
hepatitis C infection
MGH study reveals mechanism
key to maintaining chronic infection, potential therapy target
BOSTON - February 4, 2008 - A compound that naturally occurs
in grapefruit and other citrus fruits may be able to block the secretion
of hepatitis C virus (HCV) from infected cells, a process required
to maintain chronic infection. A team of researchers from the Massachusetts
General Hospital Center
for Engineering in Medicine (MGH-CEM) report that HCV is bound
to very low-density lipoprotein (vLDL, a so-called "bad"
cholesterol) when it is secreted from liver cells and that the viral
secretion required to pass infection to other cells may be blocked
by the common flavonoid naringenin.
If the results of this study extend to human patients, a combination
of naringenin and antiviral medication might allow patient to clear
the virus from their livers. The report will appear in an upcoming
issue of the journal Hepatology and has been released online.
"By finding that HCV is secreted from infected cells by latching
onto vLDL, we have identified a key pathway in the viral lifecycle,"
says Yaakov Nahmias, PhD, of the MGH-CEM, the paper's lead author.
"These results suggest that lipid-lowering drugs, as well as
supplements, such as naringenin, may be combined with traditional
antiviral therapies to reduce or even eliminate HCV from infected
HCV is the leading cause of chronic viral liver disease in the United
States and infects about 3 percent of the world population. Current
antiviral medications are effective in only half of infected patients,
70 percent of whom develop chronic infection that can lead to cirrhosis
or liver cancer. Since the virus does not integrate its genetic
material into the DNA of infected cells the way HIV does, totally
clearing the virus could be possible if new cells were not being
infected by secreted virus.
"Identifying the route by which HCV is released from cells
introduces a new therapeutic target," says Martin Yarmush,
MD, PhD, director of the MGH-CEM and the paper's senior author.
"That pathway's dependence on cholesterol metabolism could
allow us to interfere with viral propagation to other cells and
tissues, using tools already developed for atherosclerosis treatment."
Yarmush is the Helen Andrus Benedict Professor of Surgery and Bioengineering
at Harvard Medical School (HMS).
Grapefruit's bitter taste is caused the presence of the flavonoid
naringin, which is metabolized into naringenin, an antioxidant previously
reported to help lower cholesterol levels. Considerable research
has suggested that HCV infects liver cells by, in essence, "hitching
a ride" onto the natural lipoprotein-cholesterol metabolic
pathway. Since earlier evidence has shown that naringenin can reduce
secretion of vLDL from liver cells, the researchers examined whether
the compound might also lower HCV secretion from infected cells.
Their experiments confirmed that naringenin does reduce the secretion
of HCV from infected cell lines and showed that the compound inhibits
the mechanism for secreting a specific lipoprotein that binds HCV.
"This work presents the possibility that non-toxic levels of
a dietary supplement, such as naringenin, could effectively block
HCV secretion," says Raymond Chung, MD, MGH director of Hepatology
and one of the study authors, "This approach might eventually
be used to treat patients who do not respond to or cannot take traditional
interferon-based treatment or be used in combination with other
agents to boost success rates."
Chung is an associate professor of Medicine at HMS, and Nahmias
is an instructor in Surgery and Bioengineering. Additional co-authors
of the Hepatology paper are Jonathan Goldwasser, Monica Casali,
PhD, Daan van Poll, MD, MGH-CEM; and Takaji Wakita, MD, Tokyo Metropolitan
Institute. The work was supported by grants from the National Institutes
of Health and Shriners Hospitals for Children.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of more than $500 million
and major research centers in AIDS, cardiovascular research, cancer,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, regenerative
medicine, systems biology, transplantation biology and photomedicine.
Media Contacts: Sue
McGreevey, MGH Public Affairs
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