Simvastatin and artesunate impact the structural organization of adult Schistosoma mansoni in hypercholesterolemic mice

Effects of multiple doses of simvastatin and artesunate monotherapy on SCHISTOSOMA MANSONI adult worms during infection in hyperlidemic mice

“…Concerning the present work, we addressed the effects of artesunate and simvastatin using a regimen in mice fed high-fat chow. Consistent with our previous reports (Neves et al, 2007a;Alencar et al, 2009Alencar et al, , 2016; da Silva Filomeno et al, 2020), feeding high-fat chow (UHFC) increased levels of total cholesterol (TC) compared with that of standard chow-fed control mice (USC).…”

“…Having identified such alterations by light microscopy, we further analyzed the reproductive system using confocal microscopy. Consistent with our previous study, simvastatin (HFCS) and artesunate (HFCA) treatment induced morphological alterations in testicular lobes characterized by cellular disorganization, immature cells without sperm formation or low density of spermatozoa within the seminal vesicle, when compared to normal features observed in untreated worms (USC and UHFC) (Alencar et al, 2016).…”

“…The current findings provide evidence that both drugs reduced the worm burden by 54% (HFCS) or 73% (HFCA). It is interesting to contrast the results obtained here with our previous study using a single dose, in which artesunate-treated mice showed lower worm burden reduction (HFCA, 49%) (Alencar et al, 2016). This suggests that the long-term treatment could potentially increase the antischistosomal activity of artesunate, regardless of diet (Araújo et al, 1999;Shaohong et al, 2006).…”

“…Evidence indicates that host diet has an influence on the development of adult worms and over the course of S. mansoni infection (Marques et al, 2018). During the last few years, our group has shown that in a cholesterol-rich environment, schistosomes increase infectivity rate, fertility and egg maturity, when compared to worms kept on normal mouse chow (Neves et al, 2007a;Alencar et al, 2016). We here corroborate that high-fat feeding results in higher adult worm recovery (HFCS), but no statistical difference was found (Alencar et al, 2016).…”

“…Besides all of the reasons aforementioned of limitations in the schistosomicidal drug's efficacy, the role of the host diet on the chemotherapeutic treatment is lacking (Augusto et al, 2019). We recently demonstrated that a single dose of simvastatin (200 mg/kg) and artesunate (300 mg/kg) alone caused consistent damage to the reproductive system of schistosomes (testicular lobes, vitelline glands and ovarian cells), as well as severe tegumental damage in male worms in mice fed high-fat chow (Alencar et al, 2016). In view of such results, we investigated whether treatment with multiple-dose regimes may offer any antischistosomal activity advantage in relation to a single daily dose in mice fed high-fat chow.…”