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In vitro killing action of auranofin on Taenia crassiceps metacestode (cysticerci) and inactivation of thioredoxin–glutathione reductase (TGR)

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Abstract

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 µM auranofin, 90% of cysticerci were alive, but respiration activity had declined by 50%. After 12 h, neither survivors nor respiration was detected; a LD50 for auranofin of 3.8 µM was calculated. Interestingly, crude extracts of cysticerci pretreated with 3 µM auranofin nearly nil TGR activity (IC50 = 0.6 µM). 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.

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Acknowledgments

We thank Karel Estrada from the Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM) for assistance in bioinformatics. This work was supported by research grant PAPIIT IN220710-3 from the Dirección General de Asuntos del Personal Académico, UNAM. The authors thank Dr. J. Edgardo Escamilla for helpful discussions and Yoame Escamilla for the video edition. All experiments reported in this work were complied according to the bioethical regulations of the Universidad Nacional Autónoma de México.

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Authors and Affiliations

  1. Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Apartado Postal 70-159, México City, 04510, Mexico

    José J. Martínez-González, Alberto Guevara-Flores, Georgina Álvarez, Juan Luis Rendón-Gómez & Irene P. del Arenal

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  1. José J. Martínez-González
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  2. Alberto Guevara-Flores
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  3. Georgina Álvarez
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  4. Juan Luis Rendón-Gómez
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  5. Irene P. del Arenal
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Correspondence to Irene P. del Arenal.

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Martínez-González, J.J., Guevara-Flores, A., Álvarez, G. et al. In vitro killing action of auranofin on Taenia crassiceps metacestode (cysticerci) and inactivation of thioredoxin–glutathione reductase (TGR). Parasitol Res 107, 227–231 (2010). https://doi.org/10.1007/s00436-010-1867-1

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