The Protective Effect of 3-Aminobenzamide on Ischemia-Reperfusion-Induced Liver Injury

3-胺基苯醯胺對缺血再灌流引發肝損傷的保護作用

林恆毅(Hen-I Lin) ； 汪大衛(David Wang) ； 蔣桂芳(Kuei-Fang Chiang) ； 陳昭富(Chao-Fuh Chen)

《輔仁醫學期刊》 2卷2期 (2004/06) Pp. 19-26

摘要

Background and Purpose: Reperfusion of an ischemic liver results in the generation of oxidative stress and nitrosative stress, both of which can cause strand breaks in DNA, thus activating nuclear enzyme poly (ADP-ribose) synthase (PARS). This results in rapid depletion of intracellular NAD+ and ATP and eventually induces irreversible cytotoxicity. In this study, we demonstrate that a PARS inhibitor, 3-aminobenzamide, attenuated ischemia/reperfusion (I/R)-induced liver injury. Methods: 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 the ischemia and after the reperfusion were analyzed for methyl guanidine (MG), NO, and white blood cells. Blood levels of aspartate transferase (AST) and alanine transferase (ALT), which serve as indices of liver injury, were measured. Results: Results showed that this protocol resulted in elevation of the blood NO level (p＜0.01). Inflammation was apparent, as white cells and MG levels were significantly increased (p＜0.05 and p＜0.001, respectively). AST and ALT were elevated to 4~5-fold of their respective baselines (both p＜0.001). After administration of 3-aminobenzamide (20mg/kg), liver injury was significantly attenuated while MG (p＜0.001) and NO (p＜0.05) releases were reduced. Conclusion: These results indicate that 3-aminobenzamide, presumably by acting through multiple functions, exerts potent anti-inflammatory effects in I/R-induced liver injury.

關鍵字

缺血再循環 ； 肝損傷 ； 氧游離基 ； 一氧化氮 ； 3-胺基苯醯胺

並列摘要

Background and Purpose: Reperfusion of an ischemic liver results in the generation of oxidative stress and nitrosative stress, both of which can cause strand breaks in DNA, thus activating nuclear enzyme poly (ADP-ribose) synthase (PARS). This results in rapid depletion of intracellular NAD+ and ATP and eventually induces irreversible cytotoxicity. In this study, we demonstrate that a PARS inhibitor, 3-aminobenzamide, attenuated ischemia/reperfusion (I/R)-induced liver injury. Methods: 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 the ischemia and after the reperfusion were analyzed for methyl guanidine (MG), NO, and white blood cells. Blood levels of aspartate transferase (AST) and alanine transferase (ALT), which serve as indices of liver injury, were measured. Results: Results showed that this protocol resulted in elevation of the blood NO level (p＜0.01). Inflammation was apparent, as white cells and MG levels were significantly increased (p＜0.05 and p＜0.001, respectively). AST and ALT were elevated to 4~5-fold of their respective baselines (both p＜0.001). After administration of 3-aminobenzamide (20mg/kg), liver injury was significantly attenuated while MG (p＜0.001) and NO (p＜0.05) releases were reduced. Conclusion: These results indicate that 3-aminobenzamide, presumably by acting through multiple functions, exerts potent anti-inflammatory effects in I/R-induced liver injury.

並列關鍵字

ischemia-reperfusion ； liver injury ； oxygen radical ； nitric oxide ； aminobenzamide