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.
Onchocerca volvulus is a parasite responsible for the disease, Onchocerciasis otherwise known as river blindness. Current treatment and control strategies are not entirely successful. This means there is a need for further studies to better understand the biology of this worm. Studies on metabolic pathways in the worm can provide valuable information to deepen our understanding of the mechanism of survival of the worm. Lipid catabolism for the provision of energy in this worm still remains to be elucidated. Knowledge of lipids composition and synthesis in this parasite has been mostly drawn from studies on filarial species other than O. volvulus itself. This is owed to the limited availability of parasite material due largely to problems with parasite cultivation and ethical demands on obtaining materials since it has a strict preference for the human host. To explore lipid catabolism in the worm itself, we performed immunohistochemical localisation of three major enzymes (A/B hydrolase, SDH and ME1) involved in lipid metabolism on paraffin processed archival O. volvulus nodules. We observed that up to 58.6% of worms in the paraffin processed nodules had detectable A/B/HD4, 51.6% had SDH and 63.3% had ME 1, most of which were stored in the muscles of the adult worm. These observations suggest that the adult O. volvulus can operate the B-oxidative pathway, The TCA cycle, and undergo anaplerotic transformation of malic acid to pyruvate to maximise energy production from lipid metabolism. This also suggests that O. volvulus has the capacity to catabolise lipids for energy even though it appears to be dependent on carbohydrate metabolism.
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