Brain phenylalanine and tyrosine levels and hepatic encephalopathy induced by CCl4 in rats.

The correlation between the levels of brain aromatic amino acids and hepatic encephalopathy induced by CCl4 was investigated in rats. CCl4 (1.0 ml/kg three times per week for over 10 weeks) caused hyperammonemia and hepatic encephalopathy in rats. The brain levels of aromatic amino acids, especially tyrosine (Tyr) and phenylalanine (Phe) in rats with hepatic encephalopathy were increased by 605% and 255% respectively from that of the corresponding controls. Furthermore, a single intraperitoneal injection of 2,4-dinitrophenol (DNP; 30 mg/kg) in CCl4-treated rats (1.0 ml/kg three times per week for 7 weeks) showed hyperammonemia and hepatic encephalopathy (loss of consciousness) elicited a marked increase of Tyr and Phe levels in the brain. In addition, the blood levels of Tyr and Phe in all rats with hepatic encephalopathy were greatly elevated as compared to controls. On the other hand, continuous injection of ammonium chloride (20 mg N/ml) into the jugular vein for 1 h caused severe hyperammonemia without loss of consciousness. The brain levels of Tyr and Phe showed no change from the corresponding controls. These results suggest that the increase of aromatic amino acids, such as Tyr and Phe, in brain produced by hyperammonemia and high blood levels of Tyr and Phe may be a critical event to the development of hepatic encephalopathy.