Artemether shows promising female schistosomicidal and ovicidal effects on the Egyptian strain of Schistosoma mansoni after maturity of infection

Abstract

Artemether is an artemisinin derivative that is used as an antimalarial drug, especially in situations where chloroquine resistance is suspected. This compound has proved to be a good prophylactic agent against schistosomiasis japonica in China. In the present study, the therapeutic efficacies of different artemether-dosing protocols were evaluated in experimentally infected mice harbouring adult Schistosoma mansoni (Egyptian strain). Mice were treated on day 46 onwards with three dosing protocols (400 mg/kg/day for 2 days; 200 mg/kg/day for 4 days; 100 mg/kg/day for 6 days) after being infected. A number of parasitological and histopathological criteria were employed in the assessment of drug efficacies compared to infected untreated control 2 weeks post-treatment. The results of the present study suggest that artemether is efficacious against the Egyptian strain of S. mansoni with total worm reductions ranging from 40.7% to 59.7% and female worm reductions ranging from 69.3% to >90%. In addition, artemether induced significant reductions, ranging from 75.2% to 82.6%, in the liver tissue egg loads as well as significant reductions, ranging from 68.8% to 78.9% in the intestinal wall egg loads. It also induced significant alterations in the oogram pattern in the intestinal mucosa of infected mice with cessation of oviposition and increased rates of dead eggs. Antipathologic activities were also evident in the amelioration of granulomas in the liver with increased ratios of healed to active ones. In conclusion, artemether could be a promising agent in the control of schistosomiasis mansoni due to its schistosomicidal effects on female worms and to its ovicidal power as well as its potentiality in the improvement of hepatic lesions.

A comparative study on the impact of two artemisinin derivatives, artemether and artesunate, on the female reproductive system of Fasciola hepatica

“…Faecal egg count reductions following treatment of liver fluke infections in sheep with artemether and artesunate have been observed, although they were not always significant and were not necessarily linked to fluke burden reductions (and any drug efficacy) (Keiser et al, 2008(Keiser et al, , 2010a. Decreases in egg production by S. mansoni following treatment with artemether and artesunate have been described by Mitsui et al (2009) and by Abdul-Ghani et al (2011) and a reduction in egg counts has also been demonstrated in Schistosoma haematobium infections in children treated with an artesunate + sulfamethoxypyrazine/pyrimethamine combination (Sissoko et al, 2009). As spermatozoa were not present in the uterus of F. hepatica, even as early as 24 h pt with artemether, it suggests that spermatogenesis and spermiogenesis were also affected by drug action; this possibility will be examined in a separate communication.…”

Effect of the in vivo activity of dihydroartemisinin against Schistosoma mansoni infection in mice

“…In addition, it has been shown that artemether presents higher activity against juvenile S. mansoni (Xiao et al 1995(Xiao et al , 2000a(Xiao et al , 2002aUtzinger et al 2000Utzinger et al , 2001Utzinger et al , 2002Abdul-Ghani et al 2011), and there are also studies reporting that artesunate is highly toxic to S. mansoni in mice (Utzinger et al 2002;Shaohong et al 2006). Given that dihydroartemisinin is the active metabolite of the mother compound artemisinins, as well as of artemether and artesunate, it is speculated that dihydroartemisinin has effect on S. mansoni.…”

Silymarin Reduces Profibrogenic Cytokines and Reverses Hepatic Fibrosis in Chronic Murine Schistosomiasis

“…The control of this Th response throughout the chronic phase may be associated with the reduction of morbidity in schistosomiasis. During acute murine infection, administration of antioxidant drugs such as curcumin (4), resveratrol (5), n-acetylcysteine (6), artemether (7), and silymarin (8) is used to reduce morbidity and prevent hepatic fibrosis. The reversal of established hepatic fibrosis at the chronic stage is directly linked to the portal hypertension, the major cause of morbidity in Schistosoma mansoni infection, and was not attained in any of these previous works.…”