1. It is known that the perfusion of rat livers with solutions containing protoporphyrin IX induces a decrease in bile flow which is not due to inhibition of bile acid secretion but rather to decreased electrolyte transport into bile. By contrast, ursodeoxycholate induces hypercholeresis, partly due to a marked stimulation of biliary bicarbonate secretion. The aim of the present work was to investigate the effect of protoporphyrin IX on ursodeoxycholate-induced choleresis in anaesthetized male Wistar rats. 2. Protoporphyrin IX infusion at rates of 10, 20 and 40 μg min −1 100 g −1 body weight into the jugular vein induced a dose-dependent inhibitory effect on bile flow as well as on bile acid and electrolyte secretion. The lowest infused rate only induced slight and non-significant changes in spontaneous bile formation and functional variables such as glycaemia, packed cell volume, blood pH, P co 2 , P o 2 and bicarbonate concentration, and in hepatic carbonic anhydrase activity. It was thus considered as a subtoxic dose. 3. Sodium taurocholate was infused (0.5 μmol min −1 100 g −1 body weight) over the second hour of the lowest dose of protoporphyrin IX infusion. In these rats, no significant changes in bile flow or bile acid and electrolyte secretion were observed as compared with animals receiving sodium taurocholate plus saline solution. 4. Bile acid secretion induced by ursodeoxycholate infusion (1 μmol min −1 100 g −1 body weight) was similar both in rats receiving ursodeoxycholate plus saline solution and in animals infused with this bile acid over the second hour of the lowest dose of protoporphyrin IX infusion. However, bile flow and biliary bicarbonate secretion induced by ursodeoxycholate were markedly impaired (− 43% and − 56%, respectively) by protoporphyrin IX. 5. These results indicate that in the rat, in vivo , protoporphyrin IX impairs bile formation in a dose-dependent manner. They suggest that the mechanism(s) involved in ursodeoxycholate-induced bicarbonate secretion, and hence hypercholeresis, are particularly sensitive to the inhibitory effect of protoporphyrin IX.

1. The activity of erythrocyte δ-aminolaevulinic acid (ALA) dehydratase and blood protoporphyrin concentrations have been measured in patients with various anaemias, a group of subjects with known lead exposure and a group of control subjects. Leucocyte ALA synthase was measured in subjects from the last two groups. 2. Erythrocyte ALA dehydratase activity was significantly depressed in the group of lead-exposed subjects and showed a highly significant negative exponential relationship with blood lead concentration. 3. Blood protoporphyrin concentrations were significantly elevated in the group of lead-exposed subjects and patients with iron-deficiency anaemia and showed a significant positive exponential relationship with blood lead concentration. 4. Comparison of the least-squares regression analysis of these relationships and incidence of false positive and false negative results indicates that erythrocyte ALA dehydratase activity is a more accurate measure of environmental and moderate industrial lead exposure than blood protoporphyrin concentrations. 5. The correlations of erythrocyte ALA dehydratase and leucocyte ALA synthase activity, and of blood protoporphyrin concentrations and leucocyte ALA synthase activity, suggest that blood protoporphyrin more accurately reflects haem synthesis than does erythrocyte ALA dehydratase activity.