Nitric Oxide in Liver Diseases

Abstract

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.

Stimulation of Inducible Nitric Oxide by Hepatitis B Virus Transactivator Protein HBx Requires MTA1 Coregulator

“…Nitric oxide modifies DNA, proteins, and lipids or interacts with transition metals and free radical residues in a variety of cell types, including macrophages and hepatocytes (8), and participates in processes leading to inflammation and tumorigenesis. In addition to studies suggesting the prominent correlation between high levels of iNOS expression and acute and chronic hepatitis B (21,22), Kane et al (23) have shown that increased levels of nitrate and N-nitroso carcinogenic compounds are associated with DNA mutagenesis in chronic hepatitis C virus infection. Interestingly, NO also mediates the antiviral activity by inhibiting the replication of HBV and lymphocytic choriomeningitis virus (24).…”

Red Sea Suberea mollis Sponge Extract Protects against CCl4‐Induced Acute Liver Injury in Rats via an Antioxidant Mechanism

“…It has various functional messengers in numerous vertebrates. The liver is an organ that is clearly influenced by NO [46]. Using different models of liver damage, the role of NO in the liver remains controversial and it may be associated with both beneficial and detrimental consequences [47].…”

Nitric Oxide is a Potential Diagnostic Marker for Hepatocellular Carcinoma

“…During the pre-HCC period, viral infection (hepatitis B and C) or other unforeseen circumstances may lead to uncontrolled, prolonged, and/or massive production of NO by inducible nitric oxide synthase (iNOS) in the liver [6]. At the same time, NO released by the tumor cells might enhance angiogenesis, which can lead to accelerated growth of the primary tumor, as well as facilitate the process of metastasis [6]. …”