Acute effects of oltipraz on adult Schistosoma mansoni and its antagonism in vitro.
Acute effects of oltipraz on adult Schistosoma mansoni and its antagonism in vitro.
复制标题
吡噻硫酮对曼氏血吸虫成虫的急性作用及其体外拮抗作用。
DOI：
10.1016/0006-2952(87)90429-1
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发表时间：
1987
影响因子：
5.8
通讯作者：
Bennett,JL
中科院分区：
文献类型：
--
作者：
Morrison,DD;Thompson,DP;Semeyn,DR;Bennett,JL
The acute effects of oltipraz on various biochemical and physiological parameters ofS. mansoniwere evaluatedin vivo(in mice) andin vitro. In vivo,oltipraz (250 mg/kg orally) caused a significant reduction in parasite glutathione levels (GSH) 1 h after treatment, with maximum depression at 3 h.In vitro,a similar depletion of parasite GSH was observed in the presence of 10 µsmallcap˜M oltipraz. GSH (1 msmallcap˜M), cysteine (1 msmallcap˜M) and methionine (1 msmallcap˜M), but neither dithiotreitol nor 2-mercaptoethanol (1 msmallcap˜M or 100 µsmallcap˜M) blocked this effect. [35S]Cysteine or [35S]cystine uptake was also significantly inhibited by 5 µsmallcap˜M oltiprazin vitro,1 h after administration. [35S]GSH formation occurred in the presence of 5 µsmallcap˜M oltipraz and the incorporation of labelled precursor into the GSH pool was comparable to control. There were no significant differences between the cysteine and cystine controls. The amplitude and frequency of schistosome surface electrical potentials were depressed 6 h afterin vivoexposure to 125 mg/kg oltipraz; schistosomes exposed to 3.5 µsmallcap˜M oltiprazin vitroexhibited a similar level of depression, 1 h after incubation. The reduction in surface electrical activity observed after 24 h incubation in 10 µsmallcap˜M oltipraz was prevented when the parasites were coincubated with 1 msmallcap˜M cysteine or 1 msmallcap˜M GSH. Furthermore, tegument potentials were depolarized significantly by 5 µsmallcap˜M oltipraz 18 h afterin vitroincubation; this was prevented by the addition of 1 msmallcap˜M cysteine. Neither cysteine nor the oxy analogue of oltipraz altered the tegument potential, indicating that cysteine does not directly affect ionic fluxes across the membrane, and that disruption of membrane conductance may contribute to the antischistosomal efficacy of oltipraz.
