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Protective effect of L ‐carnitine in ammonia‐precipitated encephalopathy in the portacaval shunted rat
Author(s) -
Therrien G,
Rose C,
Butterworth J,
Butterworth R F
Publication year - 1997
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510250310
Subject(s) - carnitine , encephalopathy , hyperammonemia , coma (optics) , medicine , hepatic encephalopathy , endocrinology , glutamine , ammonia , saline , chemistry , biochemistry , amino acid , cirrhosis , physics , optics
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.