Abstract
Infections caused by Schistosoma haematobium and Opisthorchis viverrini are classified as Group 1 biological carcinogen and it has been postulated that parasites produce oxysterol and estrogen-like metabolites that might be considered as initiators of infection-associated carcinogenesis. Chemotherapy for these helminthic infections relies on a single drug, praziquantel, (PZQ) that mainly targets the parasite. Additionally, PZQ has some major drawbacks as inefficacy against juvenile form and alone it is not capable to counteract pathologies associated to infections or prevent carcinogenesis. There is an urgent need to develop novel therapeutic approaches that not only target the parasite but also improve the pathologies associated to infection, and ultimately, counteract or/and prevent the carcinogenesis processes. Repurposing the drug in combination of compounds with different modes of action is a promising strategy to find novel therapeutics approaches against these helminthic infections and its pathologies. Here, we emphasized that using antioxidants either alone or combined with anthelmintic drugs could ameliorate tissue damage, infection-associated complications, moreover, could prevent the development of cancer associated to infections. Hence, antioxidants represent a potential adjuvant approach during treatment to reduce morbidity and mortality. Despite the success of some strategies, there is a long way to go to implement novel therapies for schistosomiasis.
Highlights
In in vitro studies performed in our laboratory, we have found that the use of antioxidants may potentiate the antischistosomal activity of the drugs
The administration of CCM to O. viverrini-infected hamsters treated with PZQ revealed that the antioxidant might be an effective chemopreventive agent against oxidative and nitrative stress derived from PZQ treatment during opisthorchiasis via induction of nuclear factor-erythroid 2-related factor 2 (Nfr2) and induced transcriptional regulation of certain genes that lead to an increase in the level of antioxidant capacity in plasma
Higher worm burden reductions following treatment with combined regimen compared to PZQ or Artemether alone in vivo; Artemisinin’s highly active against juvenile stage of parasites; Antimalarials used in combination with PZQ exhibited the increased cure rates for schistosomiasis
Summary
One-third of the global population is estimated to be infected with helminths; they are among the most prevalent infectious disease agents, and these infections remain a persistent public health problem in the developing world [1]. Infection follows exposure to freshwater containing free-swimming larval forms of the parasite which penetrate the human skin. The cercaria loses its tail to become the schistosomulum stage This developmental stage enters the bloodstream where it circulates for several weeks before the new adult schistosome takes up residence within the mesenteric veins (S. mansoni and S. japonicum) or the vesicle plexus and veins that drain the ureter and nearby pelvic organs (S. haematobium). Cases of UGS experience moderate to severe morbidity that may be followed by squamous cell carcinoma [13,15], which could be related to deposition of S. haematobium parasite ova [16,17]. Bladder cancer is a frequent and dire complication of chronic UGS. Patients with schistosomiasis may develop bladder cancer earlier than uninfected people. The severity and frequency of the sequelae of UGS and its complication are related to the intensity and duration of the infection [18,19]
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