Effects of diosgenin, a plant-derived steroid, on bile secretion and hepatocellular cholestasis induced by estrogens in the rat

Accatino L.; Pizarro M.; Solís N.; Koenig C.S.

Keywords: model, acid, electron, rat, estrogens, animals, intravenous, flow, rats, protection, plant, cell, liver, duct, ultrastructure, steroids, mechanism, ethinylestradiol, bile, secretion, estradiol, experiment, estrogen, male, cholestasis, extracts, tissue, drug, adenosine, article, lipid, intrahepatic, controlled, animal, study, vesicle, priority, administration, nonhuman, journal, triphosphatase, Rats,, Sprague-Dawley, Diosgenin, Microscopy,, Histocytochemistry, Cholestasis,, Ethinyl, glucuronide, taurocholic, (magnesium), 17, phytosterol


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-17[3-(?-D-glucuronide) (E17G) or 17 ?-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. 17?-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 Mg2+-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 Ca2+,Mg2+-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 ultrastructure 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.

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Título de la Revista: HEPATOLOGY
Volumen: 28
Número: 1
Fecha de publicación: 1998
Página de inicio: 129
Página final: 140
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-0031836072&partnerID=q2rCbXpz