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Effects of diosgenin, A plant‐derived steroid, on bile secretion and hepatocellular cholestasis induced by estrogens in the rat
Author(s) -
Accatino Luigi,
Pizarro Margarita,
Solís Nancy,
Koenig Cecilia S.
Publication year - 1998
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510280118
Subject(s) - diosgenin , steroid , cholestasis , secretion , medicine , endocrinology , chemistry , hormone , organic chemistry
Increased biliary secretion of cholesterol and lipid vesicles (unilamellae and multilamellae) induced by diosgenin (D), a plant‐derived steroid, has cytoprotective effects in the rat liver subjected to obstructive cholestasis. In this study, our aims were to investigate the following: 1) the effects of D on the bile secretory process and on the cholestasis induced by estradiol‐17β ‐(β ‐ d ‐glucuronide) (E17G) or 17 α‐ethynylestradiol (E) administration; 2) whether the potentially protective effects of D are related to D‐induced increase of biliary cholesterol and lipid lamellae; and 3) whether D has other effects capable of modifying specific bile secretory processes or preventing the cholestatic effects of estrogens. Rats were fed a standard ground chow (control group) or chow containing D for 6 days. E17G was administered i.v. to control and D‐fed rats and bile flow, bile salt output, and alkaline phosphatase excretion were examined. 17α‐E was administered from days 4 to 6 to rats fed standard chow or chow plus D for 6 days and different functional parameters of the bile secretory process as well as the ultrastructure of hepatocytes and histochemistry of alkaline phosphatase and Mg 2+ ‐adenosine triphosphatase (ATPase) were examined. D‐treatment markedly increased cholesterol and lamellar structures in bile and attenuated the acute cholestatic effects of E17G. D‐feeding prevented the decrease of taurocholate maximum secretory rate and the increase of biliary alkaline phosphatase and Ca 2+ ,Mg 2+ ‐EctoATPase (EctoATPase) excretion, as well as the increase of cholesterol/phospholipids ratio, alkaline phosphatase activity, and EctoATPase content in canalicular plasma membranes induced by E. D‐feeding did not prevent E‐induced decrease of basal bile flow, bile salt, cholesterol, and phospholipid secretory rates nor the decrease of Na + ,K + ‐ATPase activity and Na + ‐taurocholate cotransporting polypeptide (Ntcp) content in isolated sinusoidal membranes. Cholestatic alterations of canalicular domain were apparent in E‐treated rats. D administration was also associated with changes of ultraestructure and histochemistry of hepatocytes. E‐induced alterations in ultrastructure and acinar distribution and intensity of histochemical reaction of both enzymes were partially prevented by D‐feeding. We conclude that D administration, in addition to inducing a marked increase of biliary cholesterol and lipid lamellar structures output, was associated to changes in hepatocyte morphology and plasma membrane composition, enzymes activity, and histochemistry. D‐feeding attenuated the acute cholestatic effects of E17G. D‐induced increase of bile cholesterol and lipid lamellae content was not apparent when D‐fed rats received E. Despite this fact, D administration prevented some cholestatic effects of E, probably through different metabolic effects and/or direct membrane effects, not related to increased lipid lamellae excretion.