Departments of Medicine and Biochemistry, National University of Singapore, Singapore
Address for correspondence: Wei Min Hon, Ph.D., Department of Medicine, Faculty of Medicine, National University of Singapore, 10 Kent Ridge Crescent, Singapore, 119260. Voice: (65) 779 5555 ext 2368; fax: (65) 779-4112.
mdchonwm{at}nus.edu.sg
Ann. N.Y. Acad. Sci. 962: 275-295 (2002).
Research on the free radical gas, nitric oxide (NO), during
the past twenty years is one of the most rapid growing areas
in biology. NO seems to play a part in almost every organ and
tissue. However, there is considerable controversy and confusion
in understanding its role. The liver is one organ that is clearly
influenced by NO. Acute versus chronic exposure to NO has been
associated with distinct patterns of liver disease. In this
paper we review and discuss the involvement of NO in various
liver diseases collated from observations by various researchers.
Overall, the important factors in determining the beneficial
versus harmful effects of NO are the amount, duration, and site
of NO production. A low dose of NO serves to maximize blood
perfusion, prevent platelet aggregation and thrombosis, and
neutralize toxic oxygen radicals in the liver during acute sepsis
and reperfusion events. NO also demonstrates antimicrobial and
antiapoptosis properties during acute hepatitis infection and
other inflammatory processes. However, in the setting of chronic
liver inflammation, when a large sustained amount of NO is present,
NO might become genotoxic and lead to the development of liver
cancer. Additionally, during prolonged ischemia, high levels
of NO may have cytotoxic effects leading to severe liver injury.
In view of the various possible roles that NO plays, the pharmacologic
modulation of NO synthesis is promising in the future treatment
of liver diseases, especially with the emergence of selective
NO synthase inhibitors and cell-specific NO donors.
