Abstract
Infections caused by Schistosoma haematobium and Opisthorchis viverrini are classified as carcinogenic. Although carcinogenesis might be a multifactorial process, it has been postulated that these helminth produce/excrete oxysterols and estrogen-like metabolites that might act as initiators of their infection-associated carcinogenesis. Current treatment and control of these infections rely on a single drug, praziquantel, that mainly targets the parasites and not the pathologies related to the infection including cancer. Thus, there is a need to search for novel therapeutic alternatives that might include combinations of drugs and drug repurposing. Based on these concepts, we propose a novel therapeutic strategy that combines drugs with molecule antioxidants. We evaluate the efficacy of a novel therapeutic strategy to prevent the formation of putative carcinogenic metabolites precursors and DNA adducts. Firstly, we used a methodology previously established to synthesize metabolites precursors and DNA adducts in the presence of CYP450. Then, we evaluated the inhibition of their formation induced by drugs and antioxidants alone or in combination. Drugs and resveratrol alone did not show a significant inhibitory effect while N-acetylcysteine inhibited the formation of most metabolite precursors and DNA adducts. Moreover, the combinations of classical drugs with antioxidants were more effective rather than compounds alone. This strategy might be a valuable tool to prevent the initiation of helminth infection-associated carcinogenesis.
Highlights
Helminths are the most common infectious agents of humans in developing countries affecting about one-third of the world’s population [1]
A pertinent question arises: how are these metabolites derived from helminths formed? Previously our research group performed in vitro assays to observe the interaction of metabolites, similar to those derived from helminths and associated with schistosomiasis and opisthorchiasis-associated cancers, with DNA in presence or absence of CYP450 isoforms [15]
Infections caused by carcinogenic agents O. viverrini and S. haematobium affect millions of people worldwide and are important in terms of mortality and morbidity
Summary
Helminths are the most common infectious agents of humans in developing countries affecting about one-third of the world’s population [1]. Molecules 2019, 24, 3842 by infections [1,2], including schistosomiasis, one of the major neglected tropical diseases and opisthorchiasis [3] Their causative agents, Schistosoma haematobium and Opisthorchis viverrini are considered as biological carcinogenic agents of group 1, i.e., its infection leads to squamous cell carcinoma (SCC) of the urinary bladder and cholangiocarcinoma (CCA), bile duct cancer [4]. Our group indicate that schistosomes and opisthorchiids produce/excrete estrogen- and oxysterol-like metabolites that might react with host DNA leading to its oxidation or forming depurinating DNA adducts. This interaction induces mutations in the genome of adjacent host tissues that could trigger the carcinogenesis. Genomic studies identified members of the CYP450 family genes in schistosome and opisthorchiids [19,20,21]
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