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Effect of a Macrofilaricidal Agent on the Bioenergetics of Acanthocheilonema viteae as Studied by <31>^P-NMR and Biochemical Analysis

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Title: Effect of a Macrofilaricidal Agent on the Bioenergetics of Acanthocheilonema viteae as Studied by <31>^P-NMR and Biochemical Analysis
Authors: Shukla-Dave, Amita / Roy, Raja / Srivastava, V. M. L. / Bhaduri, A. P. / Chatterjee, R. K.
Issue Date: 1-Jul-1997
Publisher: 長崎大学熱帯医学研究所 / Institute of Tropical Medicine, Nagasaki University
Citation: 熱帯医学 Tropical medicine 39(1). p27-37, 1997
Abstract: <31>^P-NMR has been applied to the study on the energy metabolism of intact rodent filariids Acanthocheilonema viteae. Based on chemical shifts and analysis of worm extracts, the phosphorus components included sugar phosphates, inorganic phosphate, glycerophosphoryl choline (GPC) and -ethanolamine (GPE), phosphoenol pyruvate (PEP), nucleotide mono, -di and -tri phosphates, nicotinamide adenine dinucleotide and uridine diphosphate glucose. Effect of adulticidal candidate drug (C. D. R. I. Comp. 82/437, in its clinical phase I trial) on the bioenergetics of A. viteae adult filariids was assessed by <31>^P-NMR and revalidated by metabolic and enzymatic studies. Comp. 82/437 at the active dose of 50mg/kg, orally×5 days, showed maximum effect on day-16 post treatment. <31>^P-NMR data revealed significantly low amount of GPE (52.2%), GPC (43.5%), ATP (54.8%) and PEP (77.2%) in the treated worms. Biochemically also, ATP and PEP levels in these worms were found to be reduced by 30.9 and 44% respectively. Amongst enzymes the activity of hexokinase rose by 58%. By this enhancement, the enzyme may be able to effectively mediate the entry of extra glucose (48%), into glycolysis. On the other hand, a substantial (30%) decrease in activity seems to make phosphofructokinase a real rate limiting step in the glycolysis. This would ultimately lead to the lower production of ATP. In the energy deprived worm all the metabolic activities will gradually decline and may result in the penultimate death due to drug action. NMR observations and conventional biochemical methods substantiate the findings of one another and direct towards the hitting of bioenergetic machinery of A. viteae by macrofilaricidal agent (Comp. 82/437).
URI: http://hdl.handle.net/10069/4737
ISSN: 03855643
Type: Departmental Bulletin Paper
Appears in Collections:Volume 39, No. 1

Citable URI : http://hdl.handle.net/10069/4737

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