The biochemical studies on phalloidin-induced cholestasis in rats.
We investigated sequential changes in bile flow, serum and biliary biochemical parameters in phalloidin-induced cholestasis in rats. Intrahepatic cholestasis was induced by administration with phalloidin (500 microg/kg) for 7 days, and then the animals were allowed to survive for 1, 2, 4, 7, 14 and 28 days after the last treatment. In phalloidin-treated rats, bile flow significantly decreased up to 4 days of recovery, compared with the control animals. In contrast, serum ALP activity, LAP activity, cholesterol concentration and phospholipid concentration exhibited a marked elevation throughout the recovery periods. For biliary parameters, bilirubin excretion rate was unchanged but, cholesterol excretion rate showed a marked decrease throughout the recovery periods. These results demonstrate that some parameters, particularly important indexes of cholestasis (serum ALP, cholesterol, bile flow and so on), continued significant changes at least 4 days after the last administration of phalloidin. These results demonstrate that successive treatment with phalloidin can cause damage in most of serum and biliary parameters at a chronic stage of cholestasis. Thus, our findings may provide useful information for diagnosis of drug-induced cholestasis and help to further elucidate the biochemical mechanisms of drug-induced cholestasis in humans.
Ishizaki
K
K
Pharmacological Research Laboratory, Product Development Laboratories, Tokyo Tanabe Co. Ltd., Kita-ku, Japan.
Kinbara
S
S
Miyazawa
N
N
Takeuchi
Y
Y
Hirabayashi
N
N
Kasai
H
H
Araki
T
T
D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism; D015415:Biomarkers; D001774:Blood Chemical Analysis; D002779:Cholestasis / Q000139:chemically induced* / Q000503:physiopathology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010590:Phalloidine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D015415:Biomarkers; D010590:Phalloidine