Valiathan Ranjini, Dubey M L, Mahajan R C, Malla Nancy
Department of Parasitology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Exp Parasitol. 2006 Oct;114(2):103-8. doi: 10.1016/j.exppara.2006.02.015. Epub 2006 Apr 17.
Although pentavalent antimonials are the first-line drug for treatment of visceral leishmaniasis all over the world, yet, in India, increasing number of patients are being reported to be unresponsive to sodium stibogluconate. Verapamil, a calcium channel blocker, affects drug uptake by preventing its efflux and thereby accumulation within the cell. In the present study, effect of verapamil on in vitro susceptibility of both promastigote and amastigote stages of 15 clinical isolates and standard strain of Leishmania donovani to sodium stibogluconate was evaluated by detection of acid phosphatase. Amastigotes were found more susceptible to sodium stibogluconate than the promastigotes (p<0.05) and in the presence of verapamil, IC(50) value of sodium stibogluconate was reduced only for those isolates, which had a higher IC(50). Verapamil alone did not have any effect on the parasites. The results indicate that amastigotes are more susceptible to sodium stibogluconate than promastigotes and verapamil can reverse the in vitro drug resistance of L. donovani clinical isolates to sodium stibogluconate.
尽管五价锑剂是全球治疗内脏利什曼病的一线药物，但在印度，据报道对葡萄糖酸锑钠无反应的患者数量不断增加。维拉帕米是一种钙通道阻滞剂，通过阻止药物外流从而影响其在细胞内的积累来影响药物摄取。在本研究中，通过检测酸性磷酸酶评估了维拉帕米对15株临床分离株和杜氏利什曼原虫标准株的前鞭毛体和无鞭毛体阶段对葡萄糖酸锑钠的体外敏感性的影响。发现无鞭毛体比前鞭毛体对葡萄糖酸锑钠更敏感（p<0.05），并且在维拉帕米存在的情况下，仅对那些IC(50)较高的分离株，葡萄糖酸锑钠的IC(50)值降低。单独的维拉帕米对寄生虫没有任何影响。结果表明，无鞭毛体比前鞭毛体对葡萄糖酸锑钠更敏感，并且维拉帕米可以逆转杜氏利什曼原虫临床分离株对葡萄糖酸锑钠的体外耐药性。
