Effect of irradiation on the activity of the major enzymes implicated in bile acid biosynthesis in the rat
M. Souidi, P. Scanff, S. Grison, D Mathe, J Aigueperse, N.M. Griffiths
XVII International Bile-Acid Meeting, Freiburg (Germany), 2002, may 30-june 1.
Radiation induced changes of the enterohepatic recycling of bile acids are manifested by alteration of intestinal bile acid reabsorption, modification of hepatic bile acid secretion and changes of the pool of bile acid reaching the intestine (Scanff et al., Int. J. Radiat. Biol, 78 (1),41-47,2002). This suggests that hepatic bile acid biosynthetic pathways may be changed: either the neutral pathway implicating cholesterol 7alpha-hydroxylase (CYP7A1) and sterol 12alpha-hydroxylase (CYP8B1) or the acidic pathway initiated by sterol 27-hydroxylase (CYP27A1) and oxysterol 7alpha-hydroxylase (CYP7B1) or both.
The aim of this work was to determine the activities of these four major enzymes implicated in bile acid biosynthesis after exposure to ionising radiation. This study was carried out in the rat 3 days after a whole body 8 Gy gamma 60Co irradiation. In the liver, irradiation leads to a decreased activity of CYP7B1 (-50%) and increased activity of CYP8B1 (3 fold). On the other hand, activity of both CYP27A1 and CYP7A1 was not modified. Concomitantly, a marked increase of the hydrophobicity index associated notably with high level of the taurodeoxycholate and taurohyodeoxycholate were observed in bile.
These results show, for the first time, that exposure to ionising radiation leads to a modulation of CYP7B1 and CYP8B1 activities which may explain the altered profile observed in the bile of irradiated rats. Thus, irradiation which modifies enterohepatic recirculation of bile salts, alters metabolism of bile acids by affecting some of the major enzymatic activities implicated in their biosynthesis.