Protective role of biliary cholesterol and phospholipid lamellae against bile acid-induced cell damage.
OBJECTIVE
Bile salts (BS) are cytotoxic agents, but cell damage is not observed in the hepatobiliary system. We hypothesized that biliary lipid vesicles (unilamellae and multilamellae) could have a protective role against BS-induced cytotoxicity.


METHODS
Biliary lipid lamellar secretion was induced by feeding rats with 0.5% diosgenin. Cytoprotection was assessed in bile duct-obstructed rats and by incubating human erythrocytes with sodium taurocholate.


RESULTS
Biliary cholesterol concentration increased > 300% in diosgenin-fed rats; electron microscopic examination showed a great abundance of lipid lamellar vesicles in bile and within the canaliculi. After bile duct obstruction, serum hepatic enzyme activities were significantly lower in diosgenin-fed rats. Histologically severe and confluent hepatocellular necrosis was only observed in control rats. Biliary lamellar lipid material significantly reduced the BS-induced hemolytic effect in vitro in a concentration-dependent manner. This protective effect correlated to a progressive decrease in the intermicellar BS concentration. Phosphatidylcholine or cholesterol, alone or as lamellar structures, also showed cytoprotective effect in vitro but always less than native biliary lamellae.


CONCLUSIONS
These results support the concept that native biliary cholesterol phospholipid lamellae represent an important cytoprotective factor for hepatocytes and biliary epithelial cells against BS-induced damage.
Departamento de Gastroenterología, Pontificia Universidad Católica, Santiago, Chile.
L
L
Puglielli
L
L
Amigo
M
M
Arrese
L
L
Núñez
A
A
Rigotti
J
J
Garrido
S
S
González
G
G
Mingrone
A V
AV
Greco
L
L
Accatino
D000818:Animals; D001646:Bile / Q000737:chemistry*; D001647:Bile Acids and Salts / Q000032:analysis / Q000494:pharmacology*; D001648:Bile Canaliculi / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002779:Cholestasis / Q000473:pathology; D002784:Cholesterol / Q000032:analysis* / Q000502:physiology*; D004144:Diosgenin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000166:cytology; D007425:Intracellular Membranes / Q000737:chemistry* / Q000648:ultrastructure; D008099:Liver / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D010743:Phospholipids / Q000032:analysis* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013656:Taurocholic Acid / Q000494:pharmacology
D001647:Bile Acids and Salts; D010743:Phospholipids; D013656:Taurocholic Acid; D002784:Cholesterol; D004144:Diosgenin