Hearn T J, Coleman A E, Lai J C, Griffith O W, Cooper A J
Department of Biochemistry, Cornell University Medical College, New York, New York 10021.
Hepatology. 1989 Nov;10(5):822-8. doi: 10.1002/hep.1840100512.
L-Carnitine (16 mmoles per kg, injected intraperitoneally) is reported to protect mice against subsequent injection of ammonium acetate given at the unprotected LD100. The present studies in rats show a variable protective effect of L-carnitine (16 mmoles per kg) administered 1 hr prior to an LD100 dose of ammonium acetate. Survival ranged from 100% to 35%. In two experiments, protection was highly significant; in a third experiment, L-carnitine did not protect against death but did significantly prolong time to death. Although the cause of this variability is not known, the data establish the protective effect in rats of L-carnitine given 1 hr before ammonium acetate. D-Carnitine and deoxycarnitine, chemically related analogs unable to substitute for L-carnitine metabolically, are without protective effect. The protective effect of L-carnitine is short-lived and is, for example, completely lost if ammonium acetate is given 24 hr after L-carnitine administration. In contrast, the free carnitine content of brain rises slowly but continuously for at least 24 hr following a single dose of L-carnitine. The observation that protection from ammonia toxicity is not correlated with brain carnitine levels strongly suggests a major peripheral component to the protective effect. Chronically hyperammonemic (portacaval-shunted) rats were found to have significantly depressed total and free carnitine levels in blood compared to normal and sham-operated controls. The hypocarnitinemia, but not the hyperammonemia, was completely reversed in portacaval-shunted rats given drinking water containing 10 mM L-carnitine.(ABSTRACT TRUNCATED AT 250 WORDS)
据报道，L-肉碱（16毫摩尔/千克，腹腔注射）可保护小鼠免受随后注射的、在未受保护情况下为100%致死剂量的醋酸铵的影响。目前对大鼠的研究表明，在LD100剂量的醋酸铵给药前1小时给予L-肉碱（16毫摩尔/千克），其保护作用存在差异。存活率在100%至35%之间。在两项实验中，保护作用非常显著；在第三项实验中，L-肉碱虽不能防止死亡，但能显著延长死亡时间。尽管这种差异的原因尚不清楚，但这些数据证实了在醋酸铵给药前1小时给予L-肉碱对大鼠有保护作用。D-肉碱和脱氧肉碱是化学相关的类似物，在代谢上不能替代L-肉碱，它们没有保护作用。L-肉碱的保护作用是短暂的，例如，如果在给予L-肉碱24小时后给予醋酸铵，保护作用就会完全消失。相比之下，单次给予L-肉碱后，大脑中的游离肉碱含量至少在24小时内缓慢而持续地上升。对氨毒性的保护作用与大脑肉碱水平不相关这一观察结果强烈表明，保护作用主要有外周成分。与正常和假手术对照组相比，发现慢性高氨血症（门腔分流）大鼠血液中的总肉碱和游离肉碱水平显著降低。给门腔分流大鼠饮用含10 mM L-肉碱的水后，低肉碱血症完全逆转，但高氨血症未逆转。（摘要截短于250字）
