L-tryptophan administration promotes the reversion of pre-established chronic liver injury in rats treated with carbon tetrachloride

We examined the effect of L-tryptophan (Trp) administration on the reversion of CCl4-induced chronic liver injury after hepatotoxicant withdrawal in rats. When rats treated with CCl4 twice a week for 6 weeks were released from CCl4 treatment for 2 weeks, there was an incomplete reversion of liver injury. The reversion was enhanced by 2 weeks of daily intraperitoneal administration of Trp (50 mg/kg body weight), starting just after CCl4 withdrawal. There were increases in the levels of thiobarbituric acid reactive substances, an index of lipid peroxidation, Ca2+, triglycerides, and Trp, and decreases in tryptophan 2,3-dioxygenase activity and serum triglyceride concentrations in the liver of rats treated with CCl4 for 6 weeks. Serum albumin concentrations and in vitro hepatic protein synthesis activity did not change in the CCl4-treated rats. The changes in the CCl4-treated rats were partially attenuated 2 weeks after CCl4 withdrawal. The attenuation was enhanced by 2 weeks of daily Trp administration. The increases in hepatic thiobarbituric acid reactive substances and triglycerides and the decreases in hepatic tryptophan 2,3-dioxygenase activity and serum triglyceride concentrations observed 2 weeks after CCl4 withdrawal were almost completely attenuated by Trp administration. In vitro hepatic protein synthesis in CCl4-treated and untreated rats was increased by 2 weeks of daily Trp administration. These results indicate that Trp administration promotes the reversion of pre-established chronic liver injury in rats treated with CCl4, and suggest that Trp exerts this effect by enhancing the improvement of several parameters of liver dysfunction associated with chronic liver injury and by stimulating hepatic protein synthesis.