Hepatic effects of Cimicifuga racemosa extract in vivo and in vitro.
Extracts of Cimicifuga racemosa are used frequently for menopausal complaints. Cimicifuga is well tolerated but can occasionally cause liver injury. To assess hepatotoxicity of cimicifuga in more detail, ethanolic C. racemosa extract was administered orally to rats, and liver sections were analyzed by electron microscopy. Tests for cytotoxicity, mitochondrial toxicity and apoptosis/necrosis were performed using HepG2 cells. Mitochondrial toxicity was studied using isolated rat liver mitochondria. Microvesicular steatosis was found in rats treated with > 1,000 mg/kg [DOSAGE ERROR CORRECTED] body weight cimicifuga extract. In vitro, cytotoxicity was apparent at concentrations > or =75 microg/mL, and mitochondrial beta-oxidation was impaired at concentrations > or =10 microg/mL. The mitochondrial membrane potential was decreased at concentrations > or =100 microg/mL, and oxidative phosphorylation was impaired at concenq trations > or =300 microg/mL. The mechanism of cell death was predominantly apoptosis. C. racemosa exerts toxicity in vivo and in vitro, eventually resulting in apoptotic cell death. The results are compatible with idiosyncratic hepatotoxicity as observed in patients treated with cimicifuga extracts.
Lüde
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S
Division of Clinical Pharmacology & Toxicology and Department of Research, University Hospital Basel, CH-4031 Basel, Switzerland.
Török
M
M
Dieterle
S
S
Knapp
A C
AC
Kaeufeler
R
R
Jäggi
R
R
Spornitz
U
U
Krähenbühl
S
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D031885:Cimicifuga / Q000633:toxicity*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
D010936:Plant Extracts