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.
Highlights
Since the 1970s, chemotherapy against schistosomiasis has relied on praziquantel (PZQ) which is considered the drug of choice for infection [1,2]
Drug repurposing is based on previous investigations and given that some drugs are already commercialized, novel antischistosomal drugs could quickly advance into clinical testing, diminishing the time and cost of new drug development [7]
Did the antioxidants exhibit antischistosomal activity but several antioxidants enhanced the schistosomical activity of the anthelmintics drugs
Summary
Since the 1970s, chemotherapy against schistosomiasis has relied on praziquantel (PZQ) which is considered the drug of choice for infection [1,2]. Massive and exclusive reliance on a single drug raises legitimate concern about schistosome PZQ-resistance. Studies have reported field and experimental isolates that exhibit significantly reduced susceptibility, which might be a foreshadowing for emergence of resistance [3,4]. PZQ-based treatment alone cannot reverse pathological sequelae of infection as periportal fibrosis for intestinal schistosomiasis and bladder deformity and hydronephrosis for urogenital schistosomiasis [5,6]. Taken together these considerations, there is a pressing need to search for additional therapeutics. Drug repurposing is an efficient approach to reduce time and cost of drug research and development [7,8], and/or combination of discrete biological active agents [9]
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