HEPATIC INJURY DUE TO CONDITIONED SULFO AMINO ACID DEFICIENCY

Functional and structural changes resulting from nutritional deficiency of amino acids and, specifically, of sulfo amino acids are well known. This paper will present examples of lesions resulting from drainage of sulfo amino acids from the body or from biological antagonism to them. Since these functional and structural changes can be prevented or corrected by additional administration of relatively large amounts of the respective amino acids, they are considered examples of conditioned amino acid deficiency. Bromobenzene combined with cysteine is excreted in the urine after acetylation. This represents a mechanism of depletion of cysteine and its precursors such as methionine from the liver and growth inhibition after administration of bromobenzene has been described.lS2 If 150 mgm. of bromobenzene is given intraperitoneally to a fasting rat, an extensive centrolobular necrosis develops within 48 hours. I t is characterized by eosinophilic necrosis, hydropic swelling and, finally, disappearance of the liver cells associated with interstitial infiltration by inflammatory cells3 (A in FIGURE 1). The lesion is more advanced in instances in which fasting for more than 12 hours precedes the bromobenzene injection and massive necrosis with hemorrhage imitating nutritional hepatic necrosis may be noted. Administration of cysteine or methionine in large doses prevents the development of the lesion (B in FIGURE 1). This already suggests the possibility that drainage of sulfo amino acids, rather than an intoxication with the halogenated benzene, causes the lesion. Chemical analyses confirm the histologic findings: I n comparison to controls, the phosphatase activity of the liver tissue is increased and the esterase and succinic dehydrogenase are significantly reduced in rats acutely intoxicated by bromobenzene. Similarly, serum bilirubin is elevated, and bromsulfalein retention is noted. I n the animals treated simultaneously with methionine and cysteine, most of these changes are either entirely prevented or a t least reduced