Postabsorption antidotal effects of N-acetylcysteine on acetaminophen-induced hepatotoxicity in the mouse.
Postabsorption antidotal effects of N-acetylcysteine on acetaminophen-induced hepatotoxicity in the mouse.
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N-乙酰半胱氨酸对乙酰氨基酚诱导的小鼠肝毒性的吸收后解毒作用。
DOI：
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发表时间：
1985
影响因子：
2.1
通讯作者：
G. Solomonraj
中科院分区：
文献类型：
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作者：
L. Whitehouse;L. Wong;C. Paul;A. Pakuts;G. Solomonraj
对乙酰氨基酚（NAPA, 350 mg/kg）给药1小时后，给予雄性瑞士韦氏小鼠n -乙酰半胱氨酸（NAC, 500 mg/kg），转氨酶水平控制，表明NAC通过吸收后解毒机制对NAPA诱导的肝毒性有保护作用。NAC可减轻NAPA引起的肝充血。naa和NAC对吲哚菁绿（500微克/千克，iv）的消除速率常数K （K = 0.676 +/- 0.062）明显高于单独接受NAPA的小鼠（0.341 +/- 0.105），表明NAC改善或保存了受损肝脏的肝循环。这种naa诱导的肝循环改善和（或）保存反映在胆和尿对乙酰氨基酚及其代谢物的排泄中，在前6小时内消除量普遍增加（70.2 +/- 2.6 vs. 32.6 +/- 7.1%），并且在NAPA消耗后，肝脏中谷胱甘肽（GSH）的补充更快地恢复到控制水平（3 vs大于5小时）。NAC在受损肝脏中的吸收后解毒作用的代谢后果是在1-4小时的胆汁中优先排出巯基衍生代谢物（GSH偶联物11.30 +/- 1.25 vs. 7.25 +/- 0.39%），随后在尿液中通过优先排出谷胱甘肽降解产物观察到。
Male Swiss Webster mice, treated with N-acetylcysteine (NAC, 500 mg/kg po) 1 h following acetaminophen (NAPA, 350 mg/kg po) administration, had control levels of transaminases indicating that NAC protects against NAPA-induced hepatotoxicity by postabsorption antidotal mechanism(s). Hepatic congestion induced by NAPA was reduced by NAC. Significantly higher elimination rate constants (K) for indocyanine green (500 micrograms/kg, iv) in mice treated with NAPA and NAC (K = 0.676 +/- 0.062) than in animals receiving NAPA alone (0.341 +/- 0.105) suggested NAC improved or preserved the hepatic circulation of the compromised liver. This NAC-induced improvement and (or) preservation of hepatic circulation was reflected in biliary and urinary excretion of acetaminophen and its metabolites by a general increase in elimination during the first 6 h (70.2 +/- 2.6 vs. 32.6 +/- 7.1%), and in the repletion of glutathione (GSH) in the liver by a return to control levels more quickly (3 vs. greater than 5 h) following depletion by NAPA. The metabolic consequences of the postabsorption antidotal effect of NAC in the compromised liver was a preferential excretion of sulphydryl-derived metabolites in the 1-4 h bile (GSH conjugate 11.30 +/- 1.25 vs. 7.25 +/- 0.39%) which was subsequently observed in the urine by preferential excretion of glutathione degradation products.