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.