科研之友
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摘要
The antischistosomal properties of the marketed antiandrogens bicalutamide, flutamide, nilutamide and cyproterone acetate were studied both in vivo and in vitro.
Schistosoma mansoni-infected mice were treated orally with 50-400 mg/kg of the antiandrogens 3 and 7 weeks post-infection. In addition, three drug combinations of nilutamide and praziquantel (200/100, 100/100 and 100/50 mg/kg) were administered to mice harbouring adult S. mansoni. Drug effects were also monitored in vitro following exposure to antiandrogen concentrations of 1, 10 and 100 mu g/mL.
Low total worm burden reductions (5%-37%) and low to moderate female worm burden reductions (13%-75%) were achieved with the antiandrogens in the S. mansoni juvenile infection model. While flutamide and cyproterone acetate lacked activity against adult S. mansoni in vivo, low to moderate total and female worm burden reductions (0%-47%) were observed with bicalutamide. The highest total and female worm burden reductions (85% and 71%, respectively) (P < 0.001) were documented following a single 400 mg/kg dose of nilutamide. Statistically significant total (91%) and female (85%) worm burden reductions were achieved with the combination of nilutamide (200 mg/kg) and praziquantel (100 mg/kg). Schistosomes incubated with 100 mu g/mL cyproterone acetate in vitro died after 15 h. Incubation with bicalutamide, nilutamide and flutamide at 100 mu g/mL resulted in decreased movement of S. mansoni adults.
Our data indicate that the hydantoin derivative nilutamide has interesting antischistosomal properties, confirming previous results of schistosomicidal activities of this drug class.
- 出版日期2010-9
