In vitro and in vivo evaluation of nano dimedone against Leishmania major

Background: Leishmaniasis, as an intracellular parasite, has shown drugshown drug resistance and therapeutic failure in recent years. Since Dimedone (DIM) has been introduced as a new chemical compound with anti-bacterial and anti-cancer properties. The aim of this study was to investigate the potential protective role of the DIM in form of nano particle in an animal model of Leishmaniasis.Methods: DIM was synthesized using nano co-precipitation method. Nanoparticles were evaluated in terms of size, polydispersity index, zeta potential, morphology, encapsulation efficiency, stability and release amount. Cytotoxicity of DIM on Vero cell line was performed by MTT and evaluation of the effect of DIM on Leishmania major was done by counting the number of parasites compared to the control group in vitro. In histological investigations, the intensity of pathogenesis and virulence of the parasite was checked on the liver cells of the animal model by hematoxylin-eosin staining. Also, parameters of oxidative stress such as catalase, glutathione peroxidase, glutathione reductase, superoxide dismutase, nitric oxide and reactive oxygen species were compared in mouse liver tissue in different groups.Results: The zeta potential of the synthesized nanoparticles was acceptable, also the size of the nanoparticles were between ۳۰۵ to ۳۴۵ nm and the PDI was less than ۰.۳. Nanoparticles showed good stability up to ۱۲ months. The release time of nanoparticles was significantly longer than the free drugs (P < ۰.۰۵). The percentage of entrapment was ۹۵.۸%. IC۵۰ of Nano-DIM was ۶۰ μM and the reduction of intracellular parasite proliferation in Nano-DIM and Nano-PYR groups were significantly lower than free drugs. Histopathology assay in the nano groups showed that the amount of disintegration of the epithelium of the central vein of the liver and the infiltration and vacuolization of hepatocytes were less compared to the Leishmaniasis group, and also oxidative stress in the groups treated with Nano-DIM and Nano-PYR were less compared to free drugs.Conclusion: The results of this study showed that DIM can be used as a promising compound against T. gondii activity and prevent the proliferation of T. gondii in cells, as well as DIM reduce the oxidative stress damages caused by Leishmaniasis. We also observed that the nanoparticle form of DIM is less toxic and more effective compared to the free DIM.

کلیدواژه ها:

Leishmaniasis ، Dimedone ، Nanoparticle ، Oxidative stress