Xenobiotic-Metabolizing Enzymes in Trematodes

Abstract

Trematode infections occur worldwide causing considerable deterioration of human health and placing a substantial financial burden on the livestock industry. The hundreds of millions of people afflicted with trematode infections rely entirely on only two drugs (praziquantel and triclabendazole) for treatment. An understanding of anthelmintic biotransformation pathways in parasites should clarify factors that can modulate therapeutic potency of anthelmintics currently in use and may lead to the discovery of synergistic compounds for combination treatments. Despite the pronounced epidemiological significance of trematodes, there is still no adequate understanding of the functionality of their metabolic systems, including xenobiotic-metabolizing enzymes. The review is focused on the structure and functional significance of the xenobiotic-metabolizing system in trematodes. Knowledge in this field can solve practical problems related to the search for new targets for antiparasitic therapy based on a focused action on certain elements of the parasite’s metabolic system. Knowledge of the functionality of this system is required to understand the adaptation of the biochemical processes of parasites residing in the host and mechanisms of drug resistance development, as well as to select a promising molecular target for the discovery and development of new anthelmintic drugs.

Single Amino Acid Polymorphisms in the Fasciola hepatica Carboxylesterase Type B Gene and Their Potential Role in Anthelmintic Resistance

“…Furthermore, our findings suggest that CestB polymorphisms may confer advantages to the parasite in overcoming immediate environmental challenges and potentially play a role in the development of anthelmintic resistance, as previously reported [19,22]. Additionally, our experimental data are consistent with the hypothesis of enzymatic detoxification, wherein the CestB amino acid polymorphisms may bind to, sequester, or enzymatically neutralize the anthelmintic compound, thus rendering it less effective [9].…”

“…Anthelmintic resistance in parasites is a complex phenomenon involving genetic mechanisms that often require the collaboration of one or multiple genes to result in noticeable levels of resistance to anthelmintic treatment [1]. These genetic mechanisms can confer resistance through different phenotypes, including modifications in the target site of the anthelmintic [8] and/or increased enzymatic detoxification [9].…”

“…The development of anthelmintic resistance in F. hepatica is facilitated by the activity of xenobiotic metabolizing enzymes (XMEs) [8]. XMEs are present in various multicellular organisms and play a vital role in protecting against the toxicity of natural chemicals [9]. These enzymes possess the capability to deactivate xenobiotic compounds by modifying their hydrophilicity and accelerating their metabolism through a process known as biotransformation [1].…”

“…These enzymes possess the capability to deactivate xenobiotic compounds by modifying their hydrophilicity and accelerating their metabolism through a process known as biotransformation [1]. In parasitic helminths, including F. hepatica, a range of XMEs are involved, including cytochrome P450, monooxygenases, dehydrogenases, carboxylesterases, and others [9].…”

Triclabendazole-Binding Pocket Identified in <em>Fasciola hepatica </em>Carboxylesterase B

“…These enzymes have the ability to deactivate xenobiotic compounds by altering their hydrophilicity and speeding up their metabolism through a process called biotransformation [6]. Among the XMEs found in parasitic helminths, cytochrome P450, monooxygenases, dehydrogenases, and carboxylesterases, among 2 others, are involved [7]. The expression and activity of XMEs regulate the susceptibility and persistence of various drugs in humans and animals [3].…”