NITRIC-OXIDE IN THE LIVER - PHYSIOPATHOLOGICAL ROLES

Many of the known roles of arginine (e.g. in immune function, wound he aling, and protection against ammonia intoxication) are mediated by a metabolic pathway synthesising nitric oxide (NO) in the liver. Contrar y to some of the current views, liver-produced NO may be basically ben eficial, as it exerts both protective actions against tissue injury an d cytotoxic effects on invading microorganisms, parasites, or tumor ce lls. An ongoing equilibrium between NO and other NO-reactive compounds (e.g. O-2 and non-heme iron-sulphur-containing moieties) appears to b e important in this respect, even under critical conditions. Thus, NO may prevent liver tissue harm from oxidant stress. Only when this puta tive counterbalance is upset by an uncontrolled, prolonged and/or mass ive production of NO, liver tissue damage may occur leading to hepatic inflammation or even tumor development. Moreover, the currently avail able data support the working hypothesis that hepatocytes partake not only to immunoregulatory processes, but even to immune defence mechani sms. Thus, the liver constitutes an excellent model for investigations into the crosstalks regulating the production of NO which take place among not only the various networks operating inside a single hepatic cell, but even the individual types of liver cells.