The biochemical studies on phalloidin-induced cholestasis in rats

Autor: Yoshishige Takeuchi, Shigemasa Kinbara, Tsutomu Araki, Hiroshi Kasai, Norio Miyazawa, Norio Hirabayashi, Kaoru Ishizaki
Rok vydání: 1997
Předmět:
Zdroj: Toxicology Letters. 90:29-34
ISSN: 0378-4274
DOI: 10.1016/s0378-4274(96)03826-x
Popis: 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 μ/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.
Databáze: OpenAIRE
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