Effect of subversive substrates on Entamoeba histolytica thioredoxin reductase activity.

ARIAS, DIEGO G.; IGLESIAS, ALBERTO A.; GUERRERO, SERGIO A.

Villa Carlos Paz – Córdoba – Argentina

Congreso; SAIB XLIV Reunión Anual.; 2008

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> E. histolytica, usually lives and multiplies within the human gut under reduced oxygen pressure. During tissue invasion, itis exposed to increased amounts of reactive oxygen species, which are highly toxic for the parasite. The metabolic pathways used by this organism to cope with such environmental changes and redox homeostasis are a matter of our work. Recently, we characterized in E. histolytica a functional thioredoxin system, which is composed by three thioredoxins and a thioredoxin reductase (TRXR). The system serves as a reduction equivalents donor for different disulfide proteins. Our data in vitro show a central role of TRXR in the functionality of the system, being the enzyme a potential key molecular target for the development of new drugs to be used in the treatment of amoebiasis. In this work, we studied the effect of methylene blue (MB), essential oils from Bystropogon mollis (“peperina”) and Thymus vulgaris (“tomillo”) on the TRXR activity. Results agree with the view that these compounds are subversive substrates of the enzyme, as they stimulate its oxidase activity with a concomitant inhibition of the disulfide reductase activity. This work strongly supports the potentiality of both essential oils and MB for designing new anti-parasite agents to treat emergent cases of amoebiasis resistant to conventional drugs.