In vitro killing action of auranofin on Taenia crassiceps metacestode (cysticerci) and inactivation of thioredoxin-glutathione reductase (TGR).
Control of cellular redox homeostasis is a central issue for all living organisms. Glutathione and thioredoxin enzymatic redox systems are the usual mean used to achieve such a control. However, parasitic platyhelminths studied to date possess a nicotinamide adenine dinucleotide phosphate-dependent thioredoxin-glutathione reductase (TGR) as the sole redox control system. Thus, TGR is considered as a potential therapeutic target of parasitic platyhelminths, and based on this assumption, the gold compound auranofin is a potent inhibitor of TGR. The aim of this research was to investigate the effect of auranofin on metacestode (cysticerci) of Taenia crassiceps in culture. Accordingly, the time course for viability and respiration of cysticerci in culture was evaluated in the presence of this compound. After 4 h at 10 microM auranofin, 90% of cysticerci were alive, but respiration activity had declined by 50%. After 12 h, neither survivors nor respiration was detected; a LD(50) for auranofin of 3.8 microM was calculated. Interestingly, crude extracts of cysticerci pretreated with 3 microM auranofin nearly nil TGR activity (IC(50) = 0.6 microM). Zymography for TGR in polyacrylamide gel electrophoresis was conducted because the previously mentioned extracts clearly showed a dose-response inactivation of TGR toward auranofin. The killing of cysticerci by this gold compound is most likely related with TGR inactivation. Therefore, further research on the suitability of auranofin as a therapeutic tool in the treatment of cysticercosis in animals and humans is sustained.
Martínez-González
José J
JJ
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Apartado Postal 70-159, México City, 04510, Mexico.
Guevara-Flores
Alberto
A
Alvarez
Georgina
G
Rendón-Gómez
Juan Luis
JL
Del Arenal
Irene P
IP
D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D001310:Auranofin / Q000494:pharmacology*; D003552:Cysticercus / Q000187:drug effects*; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D015801:Helminth Proteins / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D012119:Respiration / Q000187:drug effects; D016019:Survival Analysis; D013621:Taenia / Q000187:drug effects*; D013997:Time Factors
D000871:Anthelmintics; D004791:Enzyme Inhibitors; D015801:Helminth Proteins; D009097:Multienzyme Complexes; D001310:Auranofin; D009247:NADH, NADPH Oxidoreductases; C466433:thioredoxin glutathione reductase