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 (1 6 mmol/kg, intraperitoneally [ip]) was administered 1 hour before ammo nium acetate (NH4OAc) (8.5 mmol/kg, subcutaneously) to portacaval shun ted (PCS) rats. Cerebrospinal fluid (CSF) ammonia, lactate, and amino acid levels were measured in relation to deteriorating neurological st atus in these animals. None of 35 L-carnitine-treated animals showed n eurological deterioration after NH(4)OAC administration compared with saline-treated controls; the latter manifested severe encephalopathy p rogressing through loss of righting reflex to coma. Survival rate was 100% in the L-carnitine-treated group compared with 5% in saline-treat ed controls. Following NH(4)OAC administration to PCS rats, CSF ammoni a increased to 0.93 +/- 0.15 mmol/L and 1.24 +/- 0.15 mmol/L at precom a 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-c arnitine accumulation. CSF alanine and lactate increases following NH( 4)OAC administration to PCS rats were significantly attenuated followi ng 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-c arnitine in ammonia-precipitated coma in PCS rats and suggest that thi s protective effect is centrally mediated involving improved mitochond rial respiration. L-carnitine could be of therapeutic benefit in the p revention of hepatic encephalopathy precipitated by ammoniagenic condi tions in humans with chronic liver disease.