The effect of the hepatoprotector silymarin on bile secretion, with particu
lar regard to bile salt secretion, was studied in Wistar rats. Silymarin (2
5, 50, 100, and 150 mg/kg/day, i.p., for 5 days) induced a dose-dependent i
ncrease in bile flow and bile salt secretion, the maximal effect being reac
hed at a dose of 100 mg/kg/day (+17 and +49%, for bile flow and bile salt o
utput, respectively; P < 0.05). Assessment of bile salt composition in bile
revealed that stimulation of the bile salt secretion was accounted for mai
nly by an increase in the biliary secretion of beta-muricholate and, to a l
esser extent, of alpha-muricholate, chenodeoxycholate, ursodeoxycholate, an
d deoxycholate. The maximum secretory rate (T-m) of bile salts, as assessed
by infusing the non-hepatotoxic bile salt tauroursodeoxycholate i.v. at st
epwise-increasing rates, was not influenced by silymarin. The flavonolignan
also increased the endogenous bile salt pool size (+53%, P < 0.05) and bil
iary bile acid excretion after bile acid pool depletion (+54%, P < 0.05), a
measure of de novo bile salt synthesis. These results suggest that silymar
in increases the biliary excretion and the endogenous pool of bile salts by
stimulating the synthesis, among others, of hepatoprotective bile salts, s
uch as beta-muricholate and ursodeoxycholate. (C) 2000 Elsevier Science Inc
.