Reversal of ethinylestradiol induced cholestasis by Epomediol in rat. The role of liver plasma membrane fluidity

Autor: Miccio, M, Orzes, N, Lunazzi, Gc, Gazzin, Bruno, Corsi, R, Tiribelli, Claudio
Přispěvatelé: Miccio, M, Orzes, N, Lunazzi, Gc, Gazzin, Bruno, Corsi, R, Tiribelli, Claudio
Jazyk: angličtina
Rok vydání: 1989
Předmět:
Male
Cell Membrane/drug effects
Animals
Bicyclo Compounds
Heterocyclic
Bile/drug effects
Cell Membrane/drug effects
Cell Membrane/enzymology
Cholagogues and Choleretics/pharmacology*
Cholestasis/chemically induced*
Cholestasis/prevention & control
Ethinyl Estradiol/antagonists & inhibitors*
Liver/drug effects*
Liver/enzymology
Male
Membrane Fluidity/drug effects*
Rats
Rats
Inbred Strains
Sodium-Potassium-Exchanging ATPase/analysis
Terpenes/pharmacology

Heterocyclic
Sodium-Potassium-Exchanging ATPase/analysis
Inbred Strains
Liver/enzymology
Membrane Fluidity/drug effects
Cholestasis/chemically induced
Ethinyl Estradiol/antagonists & inhibitors
Liver/drug effects
Rats
Bile/drug effects
Cholagogues and Choleretics/pharmacology
Cell Membrane/enzymology
Animals
Terpenes/pharmacology
Bicyclo Compounds
Cholestasis/prevention & control
Popis: 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.
Databáze: OpenAIRE