Effect of ethinylestradiol and epomediol on bile flow and biliary lipid composition in rat
Autor: | Adriana M. Torres, Claudio Tiribelli, Joaquín V. Rodríguez, Giancarlo Lunazzi |
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Přispěvatelé: | Rodriguez, Jv, Torres, Am, Lunazzi, Giancarlo, Tiribelli, Claudio |
Jazyk: | angličtina |
Rok vydání: | 1992 |
Předmět: |
Male
Cholagogues and Choleretics Cholestasis/chemically induced Inbred Strains Ethinyl Estradiol Biochemistry Epomediol Liver/drug effects chemistry.chemical_compound Cholagogues and Choleretics/administration & dosage Membrane fluidity Bile Phospholipids Bicyclo Compounds Cholestasis Bile/secretion Heterocyclic Animals Bicyclo Compounds Heterocyclic Bile/drug effects* Bile/secretion Bile Acids and Salts/blood Bile Acids and Salts/secretion Cholagogues and Choleretics/administration & dosage Cholagogues and Choleretics/pharmacology* Cholestasis/chemically induced Cholestasis/metabolism Cholesterol/blood Cholesterol/secretion Ethinyl Estradiol/pharmacology* Liver/drug effects* Liver/metabolism Male Phospholipids/secretion Rats Rats Inbred Strains Terpenes/administration & dosage Terpenes/pharmacology Phospholipids/secretion Ethinyl Estradiol/pharmacology Cholesterol Liver Toxicity medicine.drug Liver/metabolism medicine.medical_specialty Choleretic Phospholipid Biology Cholesterol/blood Bile Acids and Salts Bile Acids and Salts/secretion Internal medicine Ethinylestradiol medicine Animals Terpenes/pharmacology Bile/drug effects Cholesterol/secretion Pharmacology Terpenes Rats Inbred Strains medicine.disease Bridged Bicyclo Compounds Heterocyclic Rats Endocrinology Bile Acids and Salts/blood Cholagogues and Choleretics/pharmacology chemistry Cholestasis/metabolism Terpenes/administration & dosage |
Popis: | Epomediol (1,3,3-trimethyl-2-oxabicyclo(2.2.2.)octan-6,7-endo,endo-diol) (EPO) is a terpenoid compound shown to reverse 17 alpha-ethinylestradiol (EE)-induced cholestasis in rat. The effect is related to the restoration of normal liver plasma membrane fluidity values. To further characterize the effect of EPO, bile flow and biliary lipid composition were measured in rats treated either with EE or EE associated with EPO. EE significantly reduced the bile flow; this reduction was prevented by concomitant treatment with EPO with an increase in the bile salt secretion rate. EPO alone showed a choleretic effect. The biliary secretion rate of cholesterol was also significantly reduced by EE while being comparable to controls in EE-EPO-treated animals. Phospholipid (PL) biliary excretion was significantly (P less than 0.002) increased by EE either alone or combined with EPO. After EE treatment, the biliary PL composition showed a reduction in phosphatidylcholine (PC) concentration with a parallel increase in lyso-phosphatidylcholine (LPC) when compared to control animals (PC:LPC ratio 5.0 +/- 2.5 vs 26.8 +/- 9.9, mean +/- SD, P less than 0.005). EPO administration to EE-treated rats restored the biliary PC:LPC ratio to control values (27.6 +/- 10.6). EPO alone did not show any appreciable effect as compared to both control and EE-EPO treated animals. As increased concentrations of LPC have been reported to induce an alteration in the function of membrane lipids and membrane-associated proteins, such as regulatory enzymes for bile acid, cholesterol and phospholipid metabolism, these results suggest that the protective effect of EPO in EE-induced cholestasis may be related to the reversal of the alterations in membrane lipid composition and function induced by EE. |
Databáze: | OpenAIRE |
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