Carbohydrate Catabolism in Adult <i>Onchocerca volvulus:</i> An Immunohistochemical Study

Abstract

Abstract:Onchocerca volvulus is a parasite responsible for Onchocerciasis whose main pathology is blindness. Existing treatment and control approaches are not entirely successful, with some, fraught with safety challenges. Due to these problems, the need for developing safer and effective drugs to combat the disease has become imperative. However O. volvulus materials are restricted by ethical concerns due to its strict human preference. To overcome these concerns some researchers use animal models of closely related species to obtain biological information on O. volvulus and drugs developed from these sources of information have so far failed to kill the adult O. volvulus. Realistic targets for drug development against O. volvulus could be detected directly in O. volvulus rather than its closely related species. We performed immunohistochemical detection of three major enzymes (G6PD, LDH and PDHK2) involved in carbohydrate metabolism on paraffin processed archival O. volvulus nodules. We observed that up to 64.5% of worms in the paraffin processed nodules had detectable LDH, 61.1% had G6PD and 56.7% had PDHK2 and that most of the enzymes were stored in the muscles of the adult worm. These observations suggest that the adult O. volvulus can operate the glycolytic, Pentose and Entner-Douhoroff pathways either independently or concurrently suggesting that any drug aimed at preventing the adult worm from utilising carbohydrates must target all three enzymes.

In vitro analysis of the effects of acetaminophen, ibuprofen and aspirin on motility of female adult Onchocerca volvulus worms

“…It is however possible, that amidase might not be a chokepoint enzyme. Hence, the worms could switch to alternative metabolic pathways [17] which does not require amidase and might thus increase their survivability in vitro, thereby accounting for the observed enhancement in worm motility scores in this study. It was further observed that the control group which had only medium showed the worst motility score from day 3 onward.…”

“…Therefore, the search for a microfilaricide and alternative drugs against onchocerciasis remains a top research priority (Seidu et al, 2016).…”

“…Nevertheless, in some highly endemic foci, it might be impossible to achieve elimination of the disease with a sole reliance on ivermectin [16]. Therefore, the search for a microfilaricide and alternative drugs against onchocerciasis remains a top research priority [17]. The discovery and development of new drugs requires a lot of time (10-15 years), complex and expensive processes, and the success rate has been low, only 2.01% [18].…”