Anti-angiogenic and anti-lymphangiogenic role of praziquantel and artemether in experimental mansoniasis

Angiogenesis is one of the pillars of neoplasia. Lymphangiogenesis in context of granulomas is not yet understood. This study aimed to evaluate the role of praziquantel (PZQ) and artemether (ART) as anti-angiogenic and anti-lymphangiogenic drugs in Schistosoma mansoni induced experimental hepatic model through immunohistochemical and serological studies, this can be used as a potential novel prophylactic approach in hepatic malignancy prevention and possible management. Forty female CD 1 Swiss albino mice were used divided into 4 groups (10 mice each); control healthy, control infected untreated, PZQ-treated and ART-treated. Angiogenic and lymphangiogenic effect of the drugs assessed pathologically through counting of the newly formed capillaries and lymphatics that immunohistochemically expressed by vascular Endothelial Growth Factor (VEGF), CD34 and D2-40 in liver sections using Cell Image Analyzer and serologically by evaluation of serum level of Tumor Necrosis Factor-Alpha (TNF-alpha). Our results showed significant decrease in serum TNF-alpha in ART-treated group compared to control infected and PZQ treated groups. ART exhibited significant anti-angiogenic role on granulomas illustrated by remarkable milder intensity and significantly lower expression values of VEGF and CD34 immunostaining compared to PZQ and non-treated groups. Also, ART treated group exhibited negative D2-40 expression in the granulomas in contrast to the other groups, supporting the potent ART' anti-lymphangiogenic role that exceeded PZQ. In conclusion, ART showed not only anti-angiogenic effect but also prominent anti-lymphangiogenic effect on hepatic S. mansoni granulomas compared to PZQ. Our study supports the potential use of ART as a potential novel prophylactic approach in hepatic malignancy prevention and possible management.