Kaur Sukhbir, Sachdeva Heena, Dhuria Shivani, Sharma Meenakshi, Kaur Tejinder
Parasitology Laboratory, Department of Zoology, Panjab University, Chandigarh-160014, India.
Parasitol Int. 2010 Mar;59(1):62-9. doi: 10.1016/j.parint.2009.10.006. Epub 2009 Oct 21.
Drug development in visceral leishmaniasis is extremely vital as the existing therapeutic modalities are plagued by the unwanted twosome of toxicity and drug resistance. Antineoplastic drugs have in the past been effective against the parasitic infections, for example, miltefosine. Cisplatin is a first-generation platinum-containing drug, used in the treatment of various solid tumors. Its in vitro antileishmanial effect has already been demonstrated. In the present study, the leishmanicidal potential of two doses (0.5mg/kg body weight and 1mg/kg body weight) of the drug was studied in BALB/c mice. The antileishmanial effect of the drug was revealed by significant reduction in the parasite burden. The infected and treated animals were also found to exhibit increased DTH responses. An initial transient and reversible increase in levels of SGOT, SGPT, BUN, blood urea, creatinine and phosphorus was observed in infected animals treated with both doses of the drug. The reduction in parasite load, increase in DTH response and various biochemical parameters were more pronounced in animals treated with 1mg/kg body weight of cisplatin as compared to those treated with 0.5mg/kg body weight of the drug. Though some histopathological changes were observed in the kidneys of animals treated with 1mg/kg body weight of cisplatin, no such change was observed in mice treated with the lower dose. Thus, we have for the first time characterized the in vivo effect of cisplatin in murine experimental visceral leishmaniasis.
由于现有的治疗方法受到毒性和耐药性这两个不良因素的困扰，内脏利什曼病的药物研发极为重要。过去，抗肿瘤药物已被证明对寄生虫感染有效，例如米替福新。顺铂是第一代含铂药物，用于治疗各种实体瘤。其体外抗利什曼原虫的作用已经得到证实。在本研究中，在BALB/c小鼠中研究了该药物两个剂量（0.5mg/kg体重和1mg/kg体重）的杀利什曼原虫潜力。药物的抗利什曼原虫作用通过寄生虫负荷的显著降低得以体现。还发现受感染并接受治疗的动物表现出增强的迟发型超敏反应（DTH）。在用两种剂量药物治疗的受感染动物中，观察到血清谷草转氨酶（SGOT）、血清谷丙转氨酶（SGPT）、血尿素氮（BUN）、血尿素、肌酐和磷水平最初出现短暂且可逆的升高。与用0.5mg/kg体重药物治疗的动物相比，用1mg/kg体重顺铂治疗的动物寄生虫负荷降低、DTH反应增强以及各种生化参数变化更为明显。尽管在用1mg/kg体重顺铂治疗的动物肾脏中观察到一些组织病理学变化，但在用较低剂量治疗的小鼠中未观察到此类变化。因此，我们首次描述了顺铂在小鼠实验性内脏利什曼病中的体内作用。
