Inhibitors of the lipoxygenase pathway block development of Brugia malayi L3 in vitro

The Journal of Parasitology
H L Smith, T V Rajan

Abstract

Brugia malayi L3 molt to the L4 stage in serum-free cultures supplemented with arachidonic, linoleic, or linolenic acids and the basidiomycetous yeast Rhodotorula minuta. These fatty acids are capable of entering the eicosanoid pathway of arachidonate metabolism, the pathway responsible for generating a number of biologically active mediators, including prostaglandins, leukotrienes, and lipoxins. To determine whether this pathway was required for L3 development, we added dual inhibitors of cyclooxygenase and lipoxygenase to in vitro cultures containing B. malayi L3. These compounds significantly inhibited L3 molting. To evaluate whether 1 or both of these pathways of arachidonate metabolism were involved in molting, we tested drugs inhibiting either cyclooxygenase or lipoxygenase. Lipoxygenase inhibitors blocked L3 molting, whereas cyclooxygenase inhibitors did not. To assess whether enzymes operating downstream of lipoxygenase were also involved in L3 molting, we added inhibitors of enzymes involved in leukotriene synthesis and found they were also capable of preventing development. We tested the same inhibitor panel on Dirofilaria immitis L3. A single lipoxygenase inhibitor and inhibitors of 2 different enzymes operating down...Continue Reading

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Citations

Jul 15, 2003·Clinical Microbiology Reviews·Mairi C NoverrGary B Huffnagle
Feb 19, 2004·The Journal of Experimental Medicine·Gerard L BannenbergCharles Serhan
Jan 20, 2006·The Journal of Parasitology·Lisa M Ganley-Leal
Feb 21, 2002·Current Infectious Disease Reports·Paul B. Keiser, Thomas B. Nutman
May 12, 2012·Mediators of Inflammation·Alexandre P Rogerio, Fernanda F Anibal

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Methods Mentioned

BETA
lavage

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