Protective effect of L-carnitine in ammonia-precipitated encephalopathy in the portacaval shunted rat

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / cerebrospinal fluid
  • Ammonia / blood
  • Ammonia / cerebrospinal fluid
  • Animals
  • Carnitine / blood
  • Carnitine / cerebrospinal fluid
  • Carnitine / pharmacology*
  • Hepatic Encephalopathy / blood
  • Hepatic Encephalopathy / cerebrospinal fluid
  • Hepatic Encephalopathy / chemically induced
  • Hepatic Encephalopathy / prevention & control*
  • Lactates / cerebrospinal fluid
  • Male
  • Portasystemic Shunt, Surgical*
  • Quaternary Ammonium Compounds
  • Rats
  • Rats, Sprague-Dawley


  • Amino Acids
  • Lactates
  • Quaternary Ammonium Compounds
  • Ammonia
  • Carnitine