Influence of valtrate/isovaltrate on the hematopoiesis and metabolic liver activity in mice in vivo.
Recently, cytotoxic effects of valepotriates with an epoxide moiety have been described on mouse bone marrow early progenitor cells IN VITRO. Consequently, the possible IN VIVO toxicity of valtrate on hematopoietic precursor cells was investigated. Mice were treated i.p. with 45 and 65 mg/kg or p.o. with 45 and 1350 mg/kg of the drug. Three days after treatment, colony formation of progenitor cells (CFC-S, GM-CFC, E-CFC) was not significantly different for control and experimental groups. Furthermore, the effect of valtrate on the ability of the liver to metabolize [ (14)C]methacetin was investigated by measuring the (14)CO (2) exhalation (breath test). There was a distinct reduction of the initial exhalation of (14)CO (2) following i.p. injection of 50 mg/kg of valtrate, but no effect was found after 50 or 1500 mg/kg of p.o. These results suggest that toxicity of valtrate in vivo is restricted because the distribution of the drug via circulation is obviously small.
Braun
R
R
Institut für Arzneimittel in Bundesgesundheitsamt, Seestr. 10, D-1000 Berlin 65.
Dittmar
W
W
Hübner
G E
GE
Maurer
H R
HR