Protective effect of L-carnitine in ammonia-precipitated encephalopathy in the portacaval shunted rat.
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.
Therrien
G
G
Neuroscience Research Unit, Hopital Saint-Luc, (University of Montreal), Quebec, Canada.
Rose
C
C
Butterworth
J
J
Butterworth
R F
RF
D000596:Amino Acids / Q000134:cerebrospinal fluid; D000641:Ammonia / Q000097:blood / Q000134:cerebrospinal fluid; D000818:Animals; D002331:Carnitine / Q000097:blood / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D006501:Hepatic Encephalopathy / Q000097:blood / Q000134:cerebrospinal fluid / Q000139:chemically induced / Q000517:prevention & control*; D007773:Lactates / Q000134:cerebrospinal fluid; D008297:Male; D011170:Portasystemic Shunt, Surgical; D000644:Quaternary Ammonium Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D007773:Lactates; D000644:Quaternary Ammonium Compounds; D000641:Ammonia; D002331:Carnitine