Nitric Oxide. IV. Determinants of nitric oxide protection and toxicity in liver.

Whereas nitric oxide (NO) produced by constitutive endothelial NO synthase is protective to the liver, NO produced by the inducible NO synthase (iNOS) can be either toxic or protective depending on the conditions. The availability of selective iNOS inhibitors and mice lacking various NOS isoforms made it possible to begin to elucidate the precise roles of NO in the liver. Under conditions of redox stress, induced NO contributes to hepatic damage. However, in acute inflammatory conditions associated with cytokine exposure, NO acts as a potent inhibitor of apoptosis in the liver. Our current understanding of the mechanisms by which NO exerts both hepatoprotective and hepatotoxic actions is discussed in this themes article.