Combination Anthelmintic/Antioxidant Activity Against Schistosoma Mansoni

Abstract

Schistosomiasis is a major neglected tropical disease. Treatment for schistosomiasis with praziquantel (PZQ), which is effective against the parasite, by itself is not capable to counteract infection-associated disease lesions including hepatic fibrosis. There is a pressing need for novel therapies. Due to their biological properties, antioxidant biomolecules might be useful in treating and reverting associated pathological sequelae. Here, we investigated a novel therapy approach based on a combination of anthelmintic drugs with antioxidant biomolecules. We used a host-parasite model involving Bioamphalaria glabrata and newly transformed schistosomula (NTS) of Schistosoma mansoni. For in vitro drug screening assays, was selected several antioxidants and evaluated not only antischistosomal activity but also ability to enhance activity of the anthelmintic drugs praziquantel (PZQ) and artesunate (AS). The morphological alterations induced by compounds alone/combined were assessed on daily basis using an inverted and automated microscope to quantify NTS viability by a fluorometric-based method. The findings indicated that not only do some antioxidants improve antischistosomal activity of the two anthelmintics, but they exhibit activity per se, leading to high mortality of NTS post-exposure. The combination index (CI) of PZQ + Mel (CI = 0.80), PZQ + Resv (CI = 0.74), AS + Resv (CI = 0.34), AS + NAC (CI = 0.89), VDT + Flav (CI = 1.03) and VDT + Resv (CI = 1.06) reveal that they display moderate to strong synergism. The combination of compounds with discrete mechanisms of action might provide a valuable adjunct to contribution for treatment of schistosomiasis-associated disease.

Activity of Combinations of Antioxidants and Anthelmintic Drugs against the Adult Stage of Schistosoma mansoni

“…These results agreed with previous findings [25,26]. OXA and Curc were more active than PZQ itself ( Figure 2) in like fashion to what was seen with NTS [18]. Although the mechanism of action of these two antioxidants is uncertain, OXA might inhibit thioredoxin glutathione reductase (TGR) [25] while Curc could interfere with the ubiquitin-proteasome pathway [27].…”

“…We hypothesized that combining drugs with antioxidants not only could enhance the efficacy of the drug to eliminate the parasite but also could ameliorate disease sequelae associated with infection [16]. Previously, we evaluated several classes of drugs and antioxidants either alone or combined against newly transformed schistosomula (NTS) of S. mansoni and observed that several combinations were more active rather than drugs and antioxidant alone [17,18]. Herein, we evaluated the efficacy of this novel therapeutic strategy against adult worms of S. mansoni in vitro.…”

“…Nonetheless, the decoupling of worms occurred following 17 h of exposure. Curiously, anticancer drugs also presented an antischistosomal activity against NTS [18] counteracting one of the major drawbacks of PZQ. These anticancer drugs are kinase inhibitors, and kinases play a pivotal role in key physiological processes including egg production [24].…”

“…We speculate that this novel therapeutic approach might contribute to the treatment of schistosomiasis. Previously, this novel therapeutic approach was evaluated on the newly transformed schistosomula of S. mansoni [17,18]. Here, we evaluated these drugs and antioxidant combinations against the adult stage of S. mansoni and on oviposition by the schistosomes in vitro.…”

Pentoxifylline and/or praziquantel reduce murine schistosomiasis mansoni histopathology via amelioration of liver functions

“…PTX alone caused an increase in immature and dead eggs and a decrease in the mature eggs. This was in accordance with the findings of El-Lakkany and Nosseir (2007) and Gouveia et al (2019).…”