The effect of electron transport (ET) inhibitors and thiabendazole on the fumarate reductase (FR) and succinate dehydrogenase (SDH) of Strongyloides ratti infective (L3) larvae.
The fumarate reductase (FR) and succinate dehydrogenase (SDH) activities of isolated submitochondrial particles (SMPs) prepared from axenised L3 larvae of S. ratti were characterised with respect to their response to a selected range of inhibitors. Rotenone (a specific inhibitor of electron transport Complex I) inhibited the S. ratti FR (EC50 = 3.0 x 10(-7) M) but not SDH. This strongly suggests that the S. ratti FR is functionally linked with the S. ratti ET-Complex I. 2-Thenoyltrifluoroacetone (TTFA, an inhibitor of ET-Complex II) inhibited FR (EC50 = 2.6 x 10(-5) M) and SDH (EC50 = 2.8 x 10(-5) M) with similar effectiveness. Sodium malonate (substrate analogue of succinate) had a greater affinity for SDH (EC50 = 6.8 x 10(-4) M), than FR (EC50 = 1.9 x 10(-2) M). Sodium fumarate was ca. 8-fold more effective in inhibiting the S. ratti FR (EC50 = 6.0 x 10(-4) M) than SDH (EC50 = 4.8 x 10(-3) M). The S. ratti FR was more sensitive to inhibition by thiabendazole (TBZ; EC50 = 4.6 x 10(-4) M) than SDH (EC50 > 1.0 x 10(-3) M), suggesting that one of the sites-of-action of TBZ to be the FR of S. ratti mitochondria. More potent inhibitors of S. ratti FR, if developed, may prove to be effective chemotherapeutic agents in the management of human strongloidiasis.
Armson
A
A
School of Biomedical Sciences, Curtin University of Technology, Perth, Australia.
Grubb
W B
WB
Mendis
A H
AH
D000818:Animals; D004579:Electron Transport / Q000187:drug effects*; D005260:Female; D005650:Fumarates / Q000494:pharmacology; D007700:Kinetics; D007814:Larva; D008314:Malonates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D017170:Strongyloides ratti / Q000201:enzymology* / Q000472:pathogenicity; D013367:Submitochondrial Particles / Q000187:drug effects / Q000378:metabolism*; D013385:Succinate Dehydrogenase / Q000378:metabolism*; D013804:Thenoyltrifluoroacetone / Q000494:pharmacology*; D013827:Thiabendazole / Q000494:pharmacology*
D005650:Fumarates; D008314:Malonates; D012402:Rotenone; D013804:Thenoyltrifluoroacetone; C032005:fumaric acid; C030290:malonic acid; D013385:Succinate Dehydrogenase; D013827:Thiabendazole