Rudi Schmid

Experimental Porphyria. III. Hepatic Type Produced by Sedormid.

Summary and Conclusions 1. Allylisopro-pylacetylcarbamid (“Sedormid”) produces an hepatic form of porphyria in rabbits. 2. The livers of these animals contain large amounts of proto-, copro- and uroporphyrin, the latter chiefly in the form of non fluorescing precursors. Porphobilinogen is also present. 3. The protoporphyrin is excreted only, and the coproporphyrin chiefly, in the bile, most of the uro- type porphyrins appearing in the urine, in amounts ranging up to 60 mg in 24 hours. The latter consists mainly of type III isomers, but type I has also been identified in small amount. Large amounts of porphobilinogen are excreted in the urine. 4. The porphyrin content of erythrocytes, bone marrow, spleen, and brain is within normal limits. 5. Transient paresis of hind limbs, dilatation of the stomach, and constriction of the pylorus are noted, with irregular small bowel spasm. Death is invariably due to rupture of the stomach. 6. The possibility is discussed that the genesis of the porphyria is related to a primary effect of the Sedormid on the formation of iron porphyrin enzymes in the liver cell.

Experimental porphyria. II. Type produced by lead, phenylhydrazine and light.

Summary and Conclusions Treatment of rabbits with phenylhydrazine, lead, and light has been found to produce a temporary condition which is chemically similar to porphyria in humans. The following features are similar to those observed in human porphyria erythropoietica. a. Uroporphyrin I is excreted in the urine. Values of up to 3466 μg per day have been observed, b. The major portion of the urinary porphyrin is excreted as the free form rather than as the zinc complex, c. Bone marrow uro- and coproporphyrin values were elevated to 1500-2000 μg% as compared to normal values of approximately 0 and 5-10 μg% respectively, d. Liver porphyrin concentrations are generally normal. The following chemical features are characteristic of porphyria hepatica. a. The urinary porphobilinogen reaction is positive. This porphobilinogen has been fractionated by aluminum oxide chromatography into 2 components. The aldehyde of only one of them is extractable by N butyl alcohol, b. The increased excretion of urinary coproporphyrin is nearly all due to the type III isomer. Values ranging up to 1823 μg per day have been observed. The authors are indebted to Dr. C. J. Watson for his helpful support and encouragement of these studies.

Porphyrins in the bone marrow and circulating erythrocytes in experimental anemias.

Summary and Conclusions 1. The copro-and protoporphyrins of bone marrow and circulating erythrocytes in the rabbit have been found to exhibit dynamic changes under a variety of stimuli to erythropoiesis, including lead poisoning, phenylhydrazine, hemorrhage, and reduced oxygen tension. These consist of (1) a striking increase of coproporphyrin in the developing erythrocytes of the bone marrow, with a marked relative reduction of its concentration in circulating red blood cells, (2) an inconstant but generally increased level of protoporphyrin in the circulating as compared with the marrow erythrocytes. 2. These observations point to a close relationship between coproporphyrin and hemoglobin synthesis, and appear to be consistent with concepts which consider coproporphyrin either as a direct precursor of hemoglobin protoporphyrin or as a by-product of the synthesis. The former concept, however, seems to permit a more reasonable correlation of the porphyrin findings in bone marrow and blood with those in urine and feces.

Experimental Porphyria. I. Isolation of Uroporphyrin I from Bone Marrow of Lead Poisoned Rabbits.

Summary and Conclusions 1. Crystalline uroporphyrin I has been isolated from the bone marrow of lead poisoned rabbits and found to be identical with uroporphyrin I isolated from the urine of a patient with photosensitive (erythropoietic) porphyria. 2. The bone marrow of rabbits with acute or chronic lead poisoning has been found to contain from 15 to 844 μg of uroporphyrin I per 100 ml. 3. In experimental lead poisoning, significant amounts of uroporphyrin are found in the circulating red blood cells only during the very acute stage. Erythrocyte coproporphyrin is likewise increased markedly only during the acute phase.