Therrien G, Rose C, Butterworth J, Butterworth R F
Neuroscience Research Unit, Hopital Saint-Luc, (University of Montreal), Quebec, Canada.
Hepatology. 1997 Mar;25(3):551-6. doi: 10.1002/hep.510250310.
L-carnitine administration prevents the neurological symptoms of acute ammonia toxicity. To further evaluate its efficacy in the prevention of hepatic encephalopathy in hyperammonemic conditions, L-carnitine (16 mmol/kg, intraperitoneally [i.p.] was administered 1 hour before ammonium acetate (NH4OAc) (8.5 mmol/kg, subcutaneously) to portacaval shunted (PCS) rats. Cerebrospinal fluid (CSF) ammonia, lactate, and amino acid levels were measured in relation to deteriorating neurological status in these animals. None of 35 L-carnitine-treated animals showed neurological deterioration after NH4OAC administration compared with saline-treated controls; the latter manifested severe encephalopathy progressing through loss of righting reflex to coma. Survival rate was 100% in the L-carnitine-treated group compared with 5% in saline-treated controls. Following NH4OAC administration to PCS rats, CSF ammonia increased to 0.93 +/- 0.15 mmol/L and 1.24 +/- 0.15 mmol/L at precoma and coma stages of encephalopathy (P < .01) respectively. Treatment with L-carnitine reduced CSF ammonia at both precoma and coma stages; the time-course of this protective effect paralleled blood and CSF L-carnitine accumulation. CSF alanine and lactate increases following NH4OAC administration to PCS rats were significantly attenuated following L-carnitine treatment. However, L-carnitine treatment did not lead to significant reductions in plasma ammonia nor CSF or brain glutamine in these animals. These findings show the therapeutic efficacy of L-carnitine in ammonia-precipitated coma in PCS rats and suggest that this protective effect is centrally mediated involving improved mitochondrial respiration. L-carnitine could be of therapeutic benefit in the prevention of hepatic encephalopathy precipitated by ammoniagenic conditions in humans with chronic liver disease.
给予左旋肉碱可预防急性氨中毒的神经症状。为了进一步评估其在高氨血症情况下预防肝性脑病的疗效，在给门腔分流（PCS）大鼠皮下注射醋酸铵（NH4OAc，8.5 mmol/kg）前1小时，腹腔注射（i.p.）左旋肉碱（16 mmol/kg）。测量这些动物脑脊液（CSF）中的氨、乳酸和氨基酸水平，并观察其神经状态恶化情况。与生理盐水处理的对照组相比，35只接受左旋肉碱治疗的动物在给予NH4OAC后均未出现神经功能恶化；后者表现出严重的脑病，从翻正反射消失发展至昏迷。左旋肉碱治疗组的存活率为100%，而生理盐水处理的对照组为5%。给PCS大鼠注射NH4OAC后，在脑病的昏迷前期和昏迷期，脑脊液氨分别升至0.93±0.15 mmol/L和1.24±0.15 mmol/L（P<0.01）。左旋肉碱治疗可降低昏迷前期和昏迷期的脑脊液氨水平；这种保护作用的时间进程与血液和脑脊液中左旋肉碱的积累情况平行。左旋肉碱治疗后，PCS大鼠注射NH4OAC后脑脊液丙氨酸和乳酸的升高明显减弱。然而，左旋肉碱治疗并未使这些动物的血浆氨、脑脊液或脑谷氨酰胺显著降低。这些发现表明左旋肉碱对PCS大鼠氨诱发的昏迷具有治疗效果，并提示这种保护作用是由中枢介导的，涉及线粒体呼吸功能的改善。左旋肉碱可能对预防慢性肝病患者因产氨情况诱发的肝性脑病具有治疗益处。
