The protective effect of niacinamide on ischemia-reperfusion-induced liver injury.
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.
Chen
C F
CF
Division of Gastroenterology, Department of Internal Medicine, Cheng Hsin General Hospital,Taipei, Taiwan.
Wang
D
D
Hwang
C P
CP
Liu
H W
HW
Wei
J
J
Lee
R P
RP
Chen
H I
HI
D000255:Adenosine Triphosphate / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D006499:Hepatic Artery; D007249:Inflammation / Q000188:drug therapy; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008760:Methylguanidine / Q000097:blood; D009536:Niacinamide / Q000494:pharmacology*; D009569:Nitric Oxide / Q000097:blood; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015415:Biomarkers; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009536:Niacinamide; D009569:Nitric Oxide; D008760:Methylguanidine; D000255:Adenosine Triphosphate