Effect of protoporphyrin IX on ursodeoxycholate-induced hypercholeresis in the rat

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, Pco₂, Po₂ 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.