Nitric oxide in liver diseases: friend, foe, or just passerby?

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.