THE IDENTIFICATION OF THE ACTIVE CRYSTALLINE SUBSTANCE FROM LIVER WHICH PROTECTS AGAINST LIVER DAMAGE DUE TO CHLOROFORM OR CARBON TETRACHLORIDE; AND A STUDY OF RELATED COMPOUNDS

¹ From the Biochemical Research Foundation of the Franklin Institute, Philadelphia, Pennsylvania

1. The crystalline substance from liver extract which acts as a protective agent against the liver changes due to chloroform or carbon tetrachloride poisoning has been purified and identified as sodium xanthine.

2. The injection of sodium xanthine prepared synthetically gave the same protective activity as did the crystalline preparation from liver.

3. Other purine substances including nucleic acid, guanosine, guanine, and hypoxanthine, also were found to be protective agents. Experimental results showed adenine to be very toxic, giving unsatisfactory results. Uric acid offered a slight protection.

4. The medicinal methyl derivatives of xanthine could be tolerated by the rat only in comparatively small doses due to their pharmacological action.

5. The imidazole portion of the xanthine molecule, as represented by both histidine and imidazole itself, were inactive as protective agents.

6. The pyrimidine portion of the xanthine molecule as represented by uracil offered a very definite protective action, although somewhat different from that afforded by xanthine, or its sodium salt.

7. Purine oxidation products, allantoin and alloxan, increased the liver damage due to carbon tetrachloride or chloroform.

8. A few representative photomicrographs are included to illustrate the degree of protection afforded by several of these substances.

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