Reperfusion of ischemic liver results in the generation of
oxygen radicals,
nitric oxide (NO) and their reaction product
peroxynitrite, all of which may cause strand breaks in
DNA, which activate the nuclear
enzyme poly(ADP ribose)synthase (PARS). This results in rapid depletion of intracellular
nicotinamide adenine dinucleotide and
adenosine 5'-triphosphate (
ATP) and eventually induces irreversible cytotoxicity. In this study, we demonstrated that
niacinamide, a PARS inhibitor, attenuated
ischemia/reperfusion (I/R)-induced liver injury.
Ischemia was induced by clamping the common hepatic artery and portal vein of rats for 40 min. Thereafter, flow was restored and the liver was reperfused for 90 min. Blood samples collected prior to I and after R were analyzed for methyl
guanidine (MG), NO,
tumor necrosis factor (
TNF-alpha) and
ATP. Blood levels of
aspartate transferase (AST),
alanine transferase (ALT) and
lactate dehydrogenase (LDH) which served as indexes of liver injury were measured. This protocol resulted in elevation of the blood NO level (p < 0.01).
Inflammation was apparent, as
TNF-alpha and MG levels were significantly increased (p < 0.05 and p < 0.001). AST, ALT and LDH were elevated 4- to 5-fold (p < 0.001), while
ATP was significantly diminished (p < 0.01). After administration of
niacinamide (10 mM), liver injury was significantly attenuated, while blood
ATP content was reversed. In addition, MG,
TNF-alpha and NO release was attenuated. These results indicate that
niacinamide, presumably by acting with multiple functions, exerts potent anti-inflammatory effects in I/R-induced liver injury.