[Heme synthesis and iron turnover in rabbits with experimental lead poisoning]

The nature of anemia formation in lead poisoning is still unknown, especially of its mechanism. Rimington proposed a hypothesis that lead interferes with a specific enzyme (ferrochelatase) system, which is responsible for incorporating iron into the protoporphyrin IX molecules to form heme. In the present study, heme synthesis in mitochondria (Mt) of liver and bone marrow, and 59Fe behavior in vivo were investigated in rabbits to verify his hypothesis. The experimental five groups were as follows: 1) lead (Pb) poisoning by administration of 10-20 mg Pb/kg at a time, subcutaneously injected 10 times in all during 30 days, 2) phenylhydrazine (PH) poisoning, 10 mg PH/kg, 3 times subcutaneously during 3 days, 3) bleeding of about 105 ml of blood in total by venesection through 7 times treatments, 4) low feeding, synthetic feeding pellets of 30 g/d/cap. or 70 g/d/cap. 5) control, by administration of 5% glucose instead of lead injection with 120 g/d/cap. of the feeding pellets, with drinking water 300 ml/d/cap. for 30 days. 59Fe-plasma was prepared by the following procedure: 5 ml of plasma from each rabbit having been incubated with 5 microCi of 59Fe citrate at 37 degrees C for 30 minutes, 59Fe-plasma was purified partially by Borova's method. The prepared 59Fe-plasma was injected intravenously into the rabbits in each group. Urinary coproporphrin (CP-U), erythrocyte protoporphyrin (FFP), Hb, Ht, MCHC, reticulocyte (Rt), and protoheme formed by Mt, were determined to examine the relationship between lead and porphyrinheme metabolism. 59Fe behavior was estimated by detecting the plasma iron disappearance rate (half life time of 59Fe in plasma), 59Fe intake into erythrocytes, and the retention of 59Fe in tissues. Increase of FEP in lead poisoning was not caused by hemolysis, because FEP did not increase in PH group (Table 1). CP-U slightly increased in PH group, but not in the bleeding group (Table 2). This increase of CP-U must be due to acceleration of hematopoiesis in PH poisoning, because PH and bleeding groups showed an increase of Rt, counting 222.2 and 85.3%, respectively, at the termination of the treatment, while the Pb group did not show any obvious reticulocytosis (Table 3). PH, bleeding, and Pb(10 mg/kg) groups showed shorter half life time of 59Fe in plasma, while the 30 g/d-feeding group showed longer time (Table 8). During 100 minutes after 59Fe injection, incorporation of 59Fe into erythrocytes was higher in PH and bleeding groups than those in other treatment groups and the control (Table 9).(ABSTRACT TRUNCATED AT 400 WORDS)