Haemin enhances the in vivo efficacy of artemether against juvenile and adult Schistosoma mansoni in mice

Abstract

Among the potential alternatives to praziquantel, interestingly, the antimalarial artemether (Art) also exhibits antischistosomal properties. Previous in vitro studies suggested that Art interacts with haemin and together produce a lethal agent against schistosomes. This study investigates the in vivo effect of Art plus haemin on juvenile and adult Schistosoma mansoni worms and on their antioxidant enzymes. Infected mice were allocated into two batches each in four groups (I-IV): (I) untreated control; (II) injected with haemin (ip, 100mg/kg/day) on days26, 27, and 28 post-infection (PI) for juvenile stage and on days47, 48, and 49 PI for adult stage; (III) treated with a single oral dose of Art (300mg/kg) either after 28 or 49days PI, respectively; and (IV) received both haemin, as group (II) and Art as group (III). Half of mice for each batch were killed 72h; meanwhile, the remaining half was killed 3weeks after Art administration. Parasitological criteria of cure and worms' antioxidant enzymes were assessed. Glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), and superoxide dismutase (SOD) activities were lower in juvenile worms than adult ones and in females than males. Haemin plus Art at the juvenile and adult stages produced significant inhibition in worms' GST, GPx, and SOD activities 72h after Art treatment, compared with Art-treated group, with enhanced killing of females (96.98 and 91.47% versus 87.04 and 72.97%, respectively) and total worms (91 and 83.39% versus 75 and 59.01%, respectively) 3weeks posttreatment. In conclusion, Art plus haemin has a higher harmful effect on juvenile and adult schistosomes and antioxidant capacity than Art alone. This gives new insights into the importance of haemin in the antischistosomal properties of artemether.