Elsevier

Biochemical Pharmacology

Volume 59, Issue 8, 15 April 2000, Pages 1015-1022
Biochemical Pharmacology

Gastrointestinal and Renal Pharmacology
Effect of silymarin on biliary bile salt secretion in the rat

https://doi.org/10.1016/S0006-2952(99)00407-4Get rights and content

Abstract

The effect of the hepatoprotector silymarin on bile secretion, with particular regard to bile salt secretion, was studied in Wistar rats. Silymarin (25, 50, 100, and 150 mg/kg/day, i.p., for 5 days) induced a dose-dependent increase in bile flow and bile salt secretion, the maximal effect being reached at a dose of 100 mg/kg/day (+17 and +49%, for bile flow and bile salt output, respectively; P < 0.05). Assessment of bile salt composition in bile revealed that stimulation of the bile salt secretion was accounted for mainly by an increase in the biliary secretion of β-muricholate and, to a lesser extent, of α-muricholate, chenodeoxycholate, ursodeoxycholate, and deoxycholate. The maximum secretory rate (Tm) of bile salts, as assessed by infusing the non-hepatotoxic bile salt tauroursodeoxycholate i.v. at stepwise-increasing rates, was not influenced by silymarin. The flavonolignan also increased the endogenous bile salt pool size (+53%, P < 0.05) and biliary bile acid excretion after bile acid pool depletion (+54%, P < 0.05), a measure of de novo bile salt synthesis. These results suggest that silymarin increases the biliary excretion and the endogenous pool of bile salts by stimulating the synthesis, among others, of hepatoprotective bile salts, such as β-muricholate and ursodeoxycholate.

Section snippets

Chemicals

SIL and 3α-hydroxysteroid dehydrogenase were obtained from the Sigma Chemical Co. Sodium TUDC was a gift from Prodotti Chimici e Alimentari S.p.A. This bile salt was more than 98% pure when examined by HPLC. All the other reagents were of the highest analytical grade available from commercial sources.

Animals and treatments

Adult male Wistar rats weighing 300–350 g were used throughout. Before the experiments, the animals were maintained on a standard diet and water ad lib. and were housed in a temperature- (21–23°)

Results

SIL had little or no impact on liver integrity, as suggested by the lack of effect of SIL on the serum biochemical markers of hepatocellular injury studied, i.e. ASAT, ALAT, and ALP, at any of the doses tested (data not shown). However, a progressive, dose-dependent decrease in total body weight was recorded during the treatment (Table 1). Hence, although no significant difference in liver weight was found between SIL-treated and control rats at any dose level, the final liver-to-body weight

Discussion

In this study, we described a number of effects induced by SIL on biliary secretion that may be relevant to the understanding of the mechanisms involved in its hepatoprotective effects.

A 5-day treatment with SIL induced a dose-dependent stimulatory effect on bile flow and bile salt output (see Fig. 1). Conversely, no change in the bile salt-independent fraction of the bile flow, as measured by the y-intercept of the regression line between bile flow and the bile salt output stimulated by TUDC

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    This work was supported financially by a Research Grant from Consejo Nacional de Investigaciones Cientı́ficas y Técnicas (CONICET), Argentina. The authors are grateful to Professor Kenichi Kitani for providing us with tauro-α-MC and tauro-β-MC standards.

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