Oxamniquine, praziquantel and lovastatin association in the experimental Schistosomiasis mansoni

Abstract

In practice, chemotherapy is the main measure utilized for the control of schistosomiasis in endemic countries. The schistosomicidal drugs used, oxamniquine and praziquantel, present few side effects and a high schistosomicidal activity, thus contributing for the treatment of infection, as well as for the control of morbidity and transmission of the disease. In the 1970s, oxamniquine was very used for individual and mass treatment of schistosomiasis, presenting satisfactory results regarding efficacy and tolerance (Katz 1980). At the end of that decade, praziquantel became available for the treatment of schistosomiasis, showing good therapeutic activity and also few side effects as well. Praziquantel is now the drug of choice for the treatment of the disease caused by the three main species of the parasite that infect humans (Doenhoff et al. 2002). Taking into account the possible rise of resistance to treatment, the tolerance level of the worm to the drug, and the therapeutic failures, it is very important to search for new therapeutic alternatives for schistosomiasis. This search is now imperative, especially considering the possible interruption of oxamniquine production as a result of its higher cost, when compared to praziquantel.The association of different drugs for use in the therapeutics of various infectious diseases can serve as a mechanism to avoid, or to delay, the rise of drug resistance. In the present study, in vivo and in vitro trials were carried out on the efficacy of the treatment with lovastatin against the Schistosoma mansoni adult worms, when administered in association with oxamniquine or praziquantel in the mouse model.

Chromatographic Fingerprint Analysis and Effects of the Medicinal Plant SpeciesMitracarpus frigiduson AdultSchistosoma mansoniWorms

“…The profile of the damage caused by the exposure of the adult worms of S. mansoni to medicinal plants extracts can be determined through the observation of reduced motility, incapacity of adhesion in the culture plate by sucker cup, and tegument darkening [10, 12, 30, 31]. When the motility is lost, the worms can be considered dead [26].…”

“…The mice were divided into eight groups ( n = 10): four groups treated and noninfected and four groups treated and infected. The animal groups were infected with approximately 50 cercariae/animal (LE/BH strain), as described by Araújo et al [10]. To evaluate the possible toxicity of the different treatments, noninfected animals were divided into (A) negative control group treated with a 1% DMSO (v/v) in 0.9% NaCl solution, (B) positive control group treated with praziquantel (200 mg/kg), and (C) and (D) groups treated with MFM at 100 and 300 mg/kg diluted with saline + 1% DMSO, respectively.…”

“…Those drugs are effective against all species of schistosome; however, they do not prevent reinfection, are inactive against juvenile schistosomes, and have only a limited effect on the already developed liver and spleen lesions [6–8]. Praziquantel has a key role in population based disease control programs in most endemic countries [3, 9, 10]. The in vitro mechanism of action of this drug on adult S. mansoni worms has been well-described in the literature.…”

Characterization of Potential Drug Targets Farnesyl Diphosphate Synthase and Geranylgeranyl Diphosphate Synthase in Schistosoma mansoni

“…Statins, which are widely used in reducing hypercholesterolemia in humans via inhibition of HMGR (21)(22)(23), have been used in experimental S. mansoni infections, resulting in significant worm death (6). Statins such as mevinolin are also reported to inhibit egg production in S. mansoni, possibly due to the lack of nonsterol lipids involved in egg production (14,24). In the absence of mevinolin, parasites produced five to six times more eggs than worms cultured in mevinolin-containing media.…”

Susceptibility of a Brazilian wild rodent isolate of Schistosoma mansoni to praziquantel in mice

“…Under laboratory conditions, this efficacy against mature infection can also be assessed by worm burden reduction and oogram changes (Pellegrino et al, 1977;Botros et al, 2004;Araújo et al, 2008). It is worth mentioning that all dosages used here are included as PZQ subcurative doses, while 600 mg/kg is a curative one (Chaiworaporn et al, 2005).…”