鉛中毒家兎のPorphyrin排泄に関する研究 : 尿中Coproporphyrinと大便中Porphyrin排泄の関係

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Although many investigations have been conducted on the urinary excretion of porphyrins and their precursors in lead poisoning, controlling factors of the coproporphyrinuria are still unknown. To make clear the mechanism of the coproporphyrinuria in this poisoning, the author examined the relationship between the urinary and the fecal porphyrin excretions in lead poisoned rabbits. Experimental animals, male adult rabbits, weighing 2.5 to 3.0 kg., were prefeeded only with "Okara" for a month to remove chlorophyll derivatives from their feces. From erythrocytes free porphyrins and urinary ALA (δ-Aminolevulinic acid), PBG (Porphobilinogen) and coproporphyrin were determined as usual. Urinary and fecal uroporphyrin was estimated by the Dresel, Rimington and Tooth's method. A modified method, shown in Tab.1, was used for the determination of ether soluble porphyrins in the feces. The obtained results were as follows: (1) As shown in Tab.2, the characteristics of these fecal porphyrins were in good agreement with those of the authentic samples, i.e. coproporphyrin III, deuteroporphyrin IX, pemptoporphyrin, and protoporphyrin IX. The quantities of copro-, deutero- and proto-porphyrin were calculated by Rimington and Sveinsson's formula, and that of pemptoporphyrin was calculated directly from the extinction at the Soret maximum using 405 mμ ε0.1mM=33.3. (2) The normal contents of porphyrins in the urine and feces are shown in Tab.3. The excretion ratio of the urinary coproporphyrin (UCP) to the total fecal porphyrin (TFP) was 0.10 (s.d.=0.04), and that of fecal coproporphyrin (FCP) to the total fecal porphyrin (TFP) was 0.21 (s.d.=0.07). (3) After intermittent intravenous administrations of a small dosis of lead into normal rabbits (0.4mg/kg/day), UCP and TFP increased temporarily two to three times the normal value with marked increases of urinary ALA and PBG. The ratio of UCP/TFP remained constant at the normal level and that of FCP/TEP was slightly reduced. (Fig.2, App. Tab.1) (4) Intravenous administrations of a large dosis of lead (1.0mg/kg daily for two or six days) or subcutaneous administrations of a still larger dosis of lead (10mg/kg daily for two days), increased UCP/TFP ratio to 0.33-6.00 in accordance with the remarkable increase of UCP in the excretion of total porphyrin. Excretion of urinary PBG was depressed as against to the marked increase of urinary ALA. (Fig.1 and 3, App. Tab.2,3) (5) The marked increase of TFP excretion especially in dicarboxylic porphyrins was induced by the intravenous administration of ALA to normal rabbits, but the ratios of UCP/TFP and FCP/TFP remained almost at the normal level. When ALA was injected intravenously into chronically lead-poisoned rabbits, a temporal marked increase of UCP was observed and the increase of TFP was followed by a drop of the UCP excretion. (Fig.4, App. Tab.4,5) (6) In CCl_4-injected rabbits, some increase of UCP with a decrease of TFP was observd immediately after the intravenous administration of ALA. On the other hand, a marked increase of UCP and afterwards some increase of TFP were induced by an intravenous injection of small dosis of lead into chronically CCl_4-poisoned rabbits. (Fig.5, App. Tab.6,7,8) (7) Only a slight increase of urinary and fecal uroporphyrins was proved in the lead-poisoned rabbits. (8) In the lead-poisoned rabbits, and elevation of free protoporphyrin content in the erythrocytes was observed. Especially in mild lead-poisoned cases a high erythrocyte-free protoporphyrin content without anemia was seen. (Fig.3-(2), 5-(3)) From these results, it is concluded that in the lead poisoning an over-production of porphyrins takes place in vivo, and that in the mild lead poisoning as well as in the normal case, the porphyrin is excreted mainly as dicarboxylic porphyrins into the feces through the liver. In the severe lead poion the contrary, coproporphyrin is excessively excreted into the urine, and the most possible explanation of this finding
1968-01-20

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川端元
長崎大学医学部公衆衛生学教室

鉛中毒家兎のPorphyrin排泄に関する研究 : 尿中Coproporphyrinと大便中Porphyrin排泄の関係

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