Role of nitric oxide in liver regeneration

The liver has a remarkable ability to regenerate in response to surgical removal or chemical insult. The mechanisms regulating regenerative processes are complex, and incompletely understood. A large number genes, which are not normally expressed in the quiescent liver, are activated. Immediately after partial hepatectomy (PH) (1-6 h), nitric oxide (NO) is synthesized by liver parenchymal and nonparenchymal cells from L-arginine, via induction of the inducible form of nitric oxide synthase (iNOS). NO is a highly reactive molecule, known to be involved in diverse biological processes in nearly all aspects of life. Liver regeneration is a major area within the field of NO research. Our review describes several processes that have been suggested to be modulated by the NO released following PH, including proliferation, apoptosis and angiogenesis in the remnant tissue. Because iNOS up regulation has such profound physiologic effects, its regulation is strictly controlled. The up regulation of iNOS after PH and the subsequent production of NO induce positive effects on the regulation of early stages of the regenerative process. However, overproduction (> 100%) can have detrimental effects, including apoptosis. Thus, the iNOS induction after PH is necessary, and enough to allow for the normal regenerative process.