Reversal of ethinylestradiol-induced cholestasis by epomediol in rat. The role of liver plasma-membrane fluidity.
Epomediol (EPO) is a synthetic terpenoid compound shown to be active in increasing bile flow and some enzymatic activities of liver plasma membranes in the rat. The possible effect of EPO treatment in the ethinyl-estradiol (EE) induced cholestasis in the rat was investigated by measuring the hepatic transport of sulfobromophthalein (BSP) (plasma clearance and biliary secretion) and bile flow. Liver plasma membrane fluidity was also determined by the steady state fluorescence polarization (P) of diphenylhexatriene (DPH). EE administration (5 mg/kg s.c. for 5 days) was followed by a significant, comparable reduction (P less than 0.001) in BSP plasma clearance and biliary excretion and in bile flow. Intraperitoneal administration of EPO (100 mg/kg) to EE-treated rats restored both parameters of BSP transport, as well as bile flow, to control values. Liver plasma membrane fluidity was markedly (P less than 0.01) decreased by EE administration with a concomitant reduction (P less than 0.01) in Na+/K+-ATPase activity. EPO administration significantly increased membrane fluidity to values higher either to cholestatic (P less than 0.05) or control (P less than 0.05) animals. On the contrary, EPO did not influence Na+/K+-ATPase activity in either EE-treated or control animals. These data indicate that EPO fully reverses the impairments of BSP transport and bile flow induced by EE, possibly by reversing the decrease in liver plasma membrane fluidity induced by the synthetic estrogen. On the contrary, the EE-mediated decrease in Na+/K+-ATPase activity was not reversed by EPO.
Miccio
M
M
Dipartimento di Biochimica, University of Trieste, Italy.
Orzes
N
N
Lunazzi
G C
GC
Gazzin
B
B
Corsi
R
R
Tiribelli
C
C
D000818:Animals; D001646:Bile / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D002779:Cholestasis / Q000139:chemically induced* / Q000517:prevention & control; D004997:Ethinyl Estradiol / Q000037:antagonists & inhibitors*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis; D013729:Terpenes / Q000494:pharmacology*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D002756:Cholagogues and Choleretics; D013729:Terpenes; D004997:Ethinyl Estradiol; D000254:Sodium-Potassium-Exchanging ATPase; C031365:epomediol