Danazol induced cholestasis: pathogenetic hypothesis.
Numerous mechanisms have been proposed to account for deficient bilirubin excretion and the pathogenesis of estrogen and steroid (danazol) induced intrahepatic cholestasis. Our hypothesis is based on the fact that danazol is administered in the treatment of pulmonary emphysema because it stimulates synthesis of alpha-1 antitrypsin and that other estrogen glucuro-conjugated metabolites are P-glycoprotein substrates. We believe that genetic alterations of alpha-1 antitrypsin and P-glycoprotein, either alone or in association with known pathogenetic mechanisms, may explain the onset of danazol induced cholestasis and justify the difference in its varying duration and intensity.
Malaguarnera
M
M
Institute of Internal Medicine and Geriatrics, University of Catania, Italy.
Santangelo
N
N
Motta
M
M
Pistone
G
G
D002780:Cholestasis, Intrahepatic / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D003613:Danazol / Q000009:adverse effects*; D006801:Humans
D003613:Danazol