Auranofin-induced oxidative stress causes redistribution of the glutathione pool in Taenia crassiceps cysticerci.

Previously, we have studied the effect of the gold-compound auranofin (AF) on both thioredoxin-glutathione reductasa (TGR) activity and viability of Taenia crassiceps cysticerci. It was demonstrated that micromolar concentrations of AF were high enough to fully inhibit TGR and kill the parasites. In this work, the dynamics of changes in the glutathione pool of T. crassiceps cysticerci following the addition of AF, was analyzed. A dose-dependent decrease in the internal glutathione concentration, concomitant with an increase in ROS production was observed. These changes were simultaneous with the formation of glutathione-protein complexes and the export of glutathione disulfide (GSSG) to the culture medium. Incubation of cysticerci in the presence of both AF and N-acetyl cysteine (NAC) prevents all the above changes, maintaining cysticerci viability. By contrast, the presence of both AF and buthionine sulfoximine (BSO) resulted in a potentiation of the effects of the gold compound, jeopardizing cysticerci viability. These results suggest the lethal effect of AF on T. crassiceps cysticerci, observed at micromolar concentrations, can be explained as a consequence of major changes in the glutathione status, which results in a significant increase in the oxidative stress of the parasites.

Taenia crassiceps metacestodes have cytochrome oxidase aa3 but not cytochrome o functioning as terminal oxidase.

In mitochondria obtained from Taenia crassiceps metacestodes, carbon monoxide difference spectra reveal signals characteristic of the classical mitochondrial oxidase, cytochrome aa3, as well as signals suggesting the presence of 'cytochrome o'. In the present work, using photodissociation spectrophotometry and analysis of the haem groups, we conclude that there is no haem O in these larvae, and that the only cytochrome that functions as terminal oxidase is cytochrome c oxidase, aa3. At temperatures between -70 and -100 degrees C, the energy of activation for CO reassociation with cytochrome a3 was 10.5 kcal x mol(-1), and for oxygen binding 7.8 kcal x mol(-1).