Treatment with 3'-deoxyadenosine and deoxycoformycin in mice infected by Trypanosoma cruzi and its side effect on purinergic enzymes

Microb Pathog. 2017 Dec:113:51-56. doi: 10.1016/j.micpath.2017.10.030. Epub 2017 Oct 17.

Abstract

The aim of this study was to evaluate the efficacy of 3'-deoxyadenosine and deoxycoformycin combination in the treatment of mice infected by T. cruzi, as well as to verify the influence of the treatment on purinergic enzymes. Heart and serum samples were collected from 60 mice (30 infected and 30 uninfected) at day 12 post-infection. To verify treatment efficacy, parasitemia was monitored, and the treatment with 3'-deoxy adenosine and deoxycoformycin combination was able to reduce it, but had no curative effect on mice. Seric activities of NTPDase (ATP and ADP substrate) and ADA were increased significantly in untreated mice infected by T. cruzi compared to the negative control, as well as mice treated with 3'-deoxyadenosine and deoxycoformycin (alone or combined) modulated the activity of NTPDase (ATP and ADP substrate), preventing them from increasing in infected animals (activity similar to healthy animals). Treatment with deoxycoformycin alone and associated with 3'-deoxyadenosine modulated the activity of ADA preventing them from increasing in infected animals. However, seric activities of ADA in mice treated with 3'-deoxyadenosine (cordycepin) alone does not modify the ADA activity compared with infected and non-treated mice. However, the 5'-nucleotidase activity decreased significantly in infected untreated animals and the same occurred in infected and treated animals with deoxycoformycin and 3'-deoxyadenosine. However, treatment with deoxycoformycin associated with 3'-deoxyadenosine preventing them from decreasing the 5'-nucleotidase activity. Therefore, we conclude that the treatments did not have curative success for mice infected by T. cruzi. However, the treatments were able to modulate the purinergic enzymes during the infection by T. cruzi, which may contribute to reduce the inflammatory damage in heart.

Keywords: Cordycepin; Pathogenesis; Pentostatin; Purinergic enzymes; Trypanosoma cruzi.

MeSH terms

  • Adenosine Deaminase / metabolism
  • Animals
  • Antiprotozoal Agents / therapeutic use*
  • Chagas Disease / drug therapy*
  • Chagas Disease / parasitology
  • Deoxyadenosines / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Mice
  • Parasitemia / drug therapy*
  • Parasitemia / parasitology
  • Pentostatin / therapeutic use*
  • Pyrophosphatases / metabolism
  • Trypanosoma cruzi / drug effects*

Substances

  • Antiprotozoal Agents
  • Deoxyadenosines
  • Pentostatin
  • Adenosine Deaminase
  • Pyrophosphatases
  • cordycepin