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O0043 SOYBEAN LECITHIN IMPROVES BILIARY SECRETION AND PROTECTS AGAINST LIVER FIBROSIS IN CHOLESTATIC MDR2 KNOCK-OUT MICE

Lamireau, T.1; Bouchard, G.1; Clouzeau-Girard, H.2; Yousef, I.1; Rosenbaum, J.2; Tuchweber, B.1; Desmoulière, A.2

Journal of Pediatric Gastroenterology and Nutrition: June 2004 - Volume 39 - Issue - p S23-S24
ABSTRACTS: Oral Presentation Abstracts
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1Centre de Recherche, Hopital Sainte-Justine, Montreal, Canada,2INSERM E0362, Univeristé Victor Segalen, Bordeaux, France

Submitted by: thierry.lamireau@chu-bordeaux.fr

Introduction: Soybean lecithin has been shown to decrease the development of fibrosis in alcohol- or CCl4-induced liver disease in animals. The aim of the study was to investigate the antifibrotic properties of lecithin in Mdr2 KO mice, a model of cholestatic liver disease in which animals rapidly develop fibrosis when receiving cholic acid.

Methods: After weaning, Mdr2 KO mice were divided in 4 separated diet groups of 5–6 animals: control diet (C), control diet + 0.025% cholic acid (CA), soybean lecithin containing diet (L), and soybean lecithin containing diet + 0.025% cholic acid (L+CA). After 2 weeks, blood sample and bile were collected, then animals were sacrificed and liver was excised. Biliary concentrations of bile acids, cholesterol and phospholipid, liver lipid content, and serum liver enzyme levels (ALAT, ALP, GGT) were measured. Histological examination of the liver was performed, using cytokeratin immunostaining for bile duct proliferation, alpha-smooth muscle actin immunostaining for fibroblast activation, BrdU immunostaining for cellular proliferation, and Sirius red staining for fibrosis. A quantification was performed using image analysis.

Results: In mice receiving cholic acid (CA), body weight decreased and liver weight increased compared with other groups. Serum liver enzyme levels were markedly increased in mice receiving cholic acid (CA) but remained similar with control (C) when these animals were fed with lecithin (L+CA) (Table1). Bile flow (6.4 + 0.8 vs 4.9 + 1.7 ul/min/100gBW), and secretion of bile acids (211 + 77 vs 154 + 65 mmol/min/100gBW), phospholipid (0.19 + 0.1 vs 0.1 + 0.06 mmol/min/100gBW) and cholesterol (1.35 + 0.8 vs 0.77 + 0.63 mmol/min/100gBW) were increased in group L+CA versus group CA (p<0.01). Liver content of lipids was similar in group CA compared with group C, and was decreased in animals receiving lecithin (groups L and L+CA). Bile duct proliferation, fibroblast activation, cell proliferation in portal tracts, and liver fibrosis, were significantly increased in mice receiving cholic acid (group CA) compared with controls (group C), but remained similar to controls when animals receiving cholic acid were supplemented with lecithin (group L+CA).

Table 1

Table 1

Conclusion: This study demonstrates that soybean lecithin improves biliary secretion and liver pathology in the Mdr2 KO mice model. These observations lead to propose that clinical trials with lecithin could take place in human cholestatic diseases.

© 2004 Lippincott Williams & Wilkins, Inc.