Appraisal of Chitosan-Coated Lipid Nano-Combination with Miltefosine and Albendazole in the Treatment of Murine Trichinellosis: Experimental Study with Evaluation of Immunological and Immunohistochemical Parameters.

PURPOSE: Resistance and adverse consequences of albendazole (ABZ) in treating trichinellosis urged demand for secure and effective new drugs. The current study aimed to assess the effect of chitosan-coated lipid nano-combination with albendazole and miltefosine (MFS) in treating experimental murine trichinellosis and evaluating pathological and immunological changes of trichinellosis. MATERIALS AND METHODS: One hundred twenty Swiss albino mice were divided into six groups. Each group was subdivided into a and b subgroups based on the scarification time, which was 7- and 40-days post-infection (PI), respectively. The treatment efficacy was evaluated using parasitological, histopathological, serological (interleukin (IL)-12 and IL-4 serum levels), immunohistochemical (GATA3, glutathione peroxidase1 (GPX1) and caspase-3), and scanning electron microscopy (SEM) methods. RESULTS: The most effective drug was nanostructured lipid carriers (NLCs) loaded with ABZ (G5), which showed the most significant reduction in adults and larval count (100% and 92.39%, respectively). The greatest amelioration in histopathological changes was reported in G4 treated with MFS. GATA3 and caspase-3 were significantly reduced in all treated groups. GPX1 was significantly increased in G6 treated with MFS + NLCs. The highest degenerative effects on adults and larvae by SEM were documented in G6. CONCLUSION: Loading ABZ or MFS on chitosan-coated NLCs enhanced their efficacy against trichinellosis. Although ABZ was better than MFS, their combination should be considered as MFS caused a significant reduction in the intensity of infection. Furthermore, MFS showed anti-inflammatory (↓GATA3) and antiapoptotic effects (↓caspase-3), especially in the muscular phase. Also, when loaded with NLCS, it showed an antioxidant effect (↑GPX1).

Modulation of mice immune responses against Schistosoma mansoni infection with anti-schistosomiasis drugs: Role of interleukin-4 and interferon-gamma.

Objective: Schistosoma mansoni (S. mansoni) is endemic in Africa, the Middle East, South America, and the Caribbean. This study investigated the modulation of immune response against S. mansoni through estimation of interleukin-4 (IL-4) (Th2 cytokine) and interferon-gamma (INF-γ) (Th1 cytokine) under the effect of anti-schistosomal drugs. Methods: Laboratory bred female albino mice (n = 120) were divided into the following groups: untreated mice, S. mansoni infected mice, S. mansoni infected mice treated with artemisinin (ART), arachidonic acid (ARA), nifedipine or praziquantel (PZQ). Levels of IL-4 and INF-γ cytokines in the serum samples of treated and untreated mice were determined by enzyme-linked immunosorbent assay and the results were further validated by measuring the mRNA levels IL-4 and INF-γ using quantitative real-time polymerase chain reaction. Results: Anti-schistosomiasis drugs ART and ARA increased the levels of Th2 cytokine IL-4 (P < 0.05), whereas PZQ drug decreased the response of IL-4 (P < 0.05). However, nifedipine was found to be ineffective in modulating the response of IL-4 (P > 0.05). As far as Th-1 cytokine IFN γ was concerned, only PZQ increased its levels (P < 0.05), whereas other tested anti-schistosomiasis drugs; ART, ARA, and nifedipine were found to be infective (P > 0.05). Conclusions: These findings indicated that anti-schistosomiasis drugs ART, ARA, and PZQ play a role in the modulation of expression of Th2 cytokines. Whereas, only PZQ may play a role in the modulation of Th1 cytokines. These findings provide a scope for the formulation of novel anti-schistosomal drugs as well as in the therapeutic management of patients infected with S. mansoni.