- 作者: Chao-Fuh Chen David Wang chie Ping Hwang Hwan Wen Liu Jeng Wei Ru Ping Lee Hsing I. Chen
- 作者服務機構: Division of Gastroenterology, Department of Internal Medicine, Department of Medical research, cheng Hsin General Hospital; Departent of Physiology, National Defense Medical Center; Institute Preventive Medicine, National Defence Medical center, Taipei; Institute of Medical Sciences, Tzu chi University, Hualien, Taiwan
- 中文摘要: --
- 英文摘要: Reperfusion of ischemic liver results in the generation ofoxygen radicals, nitric oxide (NO) and their reactionproduct peroxynitrite, all of which may cause strandbreaks in DNA, which activate the nuclear enzyme po-ly(ADP ribose)synthase (PARS). This results in rapid de-pletion of intracellular nicotinamide adenine dinucleo-tide and adenosine 5'-triphosphate (ATP) and eventuallyinduces irreversible cytotoxicity. In this study, we dem-onstrated that niacinamide, a PARS inhibitor, attenuatedischemia/reperfusion (I/R)-induced liver injury. Ischemiawas induced by clamping the common hepatic arteryand portal vein of rats for 40 min. Thereafter, flow wasrestored and the liver was reperfused for 90 min. Bloodsamples collected prior to I and after R were analyzedfor methyl guanidine (MG), NO, tumor necrosis factor(TNF- ) and ATP. Blood levels of aspartate transferase(AST), alanine transferase (ALT) and lactate dehydroge-nase (LDH) which served as indexes of liver injury weremeasured. This protocol resulted in elevation of theblood NO level (p<0.01). Inflammation was apparent, asTNF- 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 dimin-ished (P< 0.01). After administration of niacinamide(10 mM), liver injury was significantly attenuated, whileblood ATP content was reversed. In addition, MG, TNF- and NO release was attenuated. These results indicatethat niacinamide, presumably by acting with multiplefunctions, exerts potent anti-inflammatory effects in I/R-induced liver injury.
- 中文關鍵字: --
- 英文關鍵字: Ischemia-Reperfusion liver injury. Methyl guanidine. Nitric oxide. Poly(ADP ribose)synthase inhibitor. Niacinamide