Protective effect of tryptophan and cysteine against carbon tetrachloride-induced liver injury

Abstract

The effects of the administration of tryptophan and/or cysteine on carbon tetrachloride (CCl 4)-induced hepatic injury were investigated. Rats received CCl 4 (1 ml/kg ip) followed 6 hr later by tryptophan (300 mg/kg) and/or cysteine (950 mg/kg) via stomach tube and rats were killed after 24 hr. Treatment with tryptophan, cysteine, or both reduced the degree of hepatic necrosis observed histologically. While CCl 4 caused polyribosomal disaggregation and decreased [ 14C]leucine incorporation into liver proteins in vitro and in vivo, treatment with tryptophan, cysteine, or both caused a shift in polyribosomes toward heavier aggregation and protein synthesis was increased. Serum activities of lactic dehydrogenase (LDH), glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and γ-glutamyl-transpeptidase were markedly increased after CCl 4 alone but after subsequent treatment with cysteine or with tryptophan and cysteine appreciable decreases occurred. Glutathione concentration decreased but total amount remained constant in the livers of CCl 4-treated rats while subsequent treatment with cysteine alone or together with tryptophan elevated both levels of glutathione. Using isolated hepatocytes, CCl 4 caused decreases in cell viability, in release of LDH, and in [ 14C]leucine incorporation into protein. Treatment with CCl 4 and tryptophan and/or cysteine revealed that cysteine alone or with tryptophan improved cell viability and decreased LDH release of the cells, while tryptophan alone or with cysteine improved protein synthesis. Upon cytologic evaluation, the isolated hepatocytes revealed membrane distortions after CCl 4 alone but these were less marked after CCl 4 plus tryptophan, cysteine, or both (most improvement). Thus, tryptophan and cysteine act in a beneficial manner against CCl 4-induced hepatic injury in the rat.